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Sample records for recessive consanguineous pakistani

  1. Genetic dissection of two Pakistani families with consanguineous localized autosomal recessive hypotrichosis (LAH)

    PubMed Central

    Abbas, Seyyedha; Naveed, Abdul Khaliq; Khan, Shakir; Yousaf, Muhammad Jawad; Azeem, Zahid; Razak, Suhail; Qaiser, Fatima

    2014-01-01

    Objective(s): Genetic analysis of two consanguineous Pakistani families with localized autosomal recessive hypotrichosis was performed with the goal to establish genotype-phenotype correlation. Materials and Methods: Genomic DNA extraction had been done from peripheral blood samples. Extracted DNA was then subjected to PCR (polymerase chain reaction) for amplification. Linkage analysis was performed using 8% polyacrylamide gel. Candidate gene was sequenced after gene linkage supported at highly polymorphic microsatellite markers of the diseased region. Results: Both families were initially tested for linkage to known genes, which were involved in human hereditary hypotrichosis, by genotyping Highly polymorphic microsatellite markers. Family B showed partial linkage at P2RY5 gene on chromosome 13q14.11-q21.32; hence, all exonic regions and their introns boundaries were subjected to DNA sequencing for any pathogenic mutation. Conclusion: Both families were tested for linkage by genotyping polymorphic microsatellite markers linked to known alopecia loci. Family A excluded all known diseased regions that is suggestive of some novel chromosomal disorder. However, sequencing of P2RY5 gene in family B showed no pathogenic mutation. PMID:25429336

  2. Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis.

    PubMed

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B

    2016-01-01

    Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information. PMID:26363620

  3. Addressing key issues in the consanguinity-related risk of autosomal recessive disorders in consanguineous communities: lessons from a qualitative study of British Pakistanis.

    PubMed

    Darr, A; Small, N; Ahmad, W I U; Atkin, K; Corry, P; Modell, B

    2016-01-01

    Currently, there is no consensus regarding services required to help families with consanguineous marriages manage their increased genetic reproductive risk. Genetic services for communities with a preference for consanguineous marriage in the UK remain patchy, often poor. Receiving two disparate explanations of the cause of recessive disorders (cousin marriage and recessive inheritance) leads to confusion among families. Further, the realisation that couples in non-consanguineous relationships have affected children leads to mistrust of professional advice. British Pakistani families at-risk for recessive disorders lack an understanding of recessive disorders and their inheritance. Such an understanding is empowering and can be shared within the extended family to enable informed choice. In a three-site qualitative study of British Pakistanis, we explored family and health professional perspectives on recessively inherited conditions. Our findings suggest, firstly, that family networks hold strong potential for cascading genetic information, making the adoption of a family-centred approach an efficient strategy for this community. However, this is dependent on provision of high-quality and timely information from health care providers. Secondly, families' experience was of ill-coordinated and time-starved services, with few having access to specialist provision from Regional Genetics Services; these perspectives were consistent with health professionals' views of services. Thirdly, we confirm previous findings that genetic information is difficult to communicate and comprehend, further complicated by the need to communicate the relationship between cousin marriage and recessive disorders. A communication tool we developed and piloted is described and offered as a useful resource for communicating complex genetic information.

  4. A missense mutation in the PISA domain of HsSAS-6 causes autosomal recessive primary microcephaly in a large consanguineous Pakistani family.

    PubMed

    Khan, Muzammil A; Rupp, Verena M; Orpinell, Meritxell; Hussain, Muhammad S; Altmüller, Janine; Steinmetz, Michel O; Enzinger, Christian; Thiele, Holger; Höhne, Wolfgang; Nürnberg, Gudrun; Baig, Shahid M; Ansar, Muhammad; Nürnberg, Peter; Vincent, John B; Speicher, Michael R; Gönczy, Pierre; Windpassinger, Christian

    2014-11-15

    Asymmetric cell division is essential for normal human brain development. Mutations in several genes encoding centrosomal proteins that participate in accurate cell division have been reported to cause autosomal recessive primary microcephaly (MCPH). By homozygosity mapping including three affected individuals from a consanguineous MCPH family from Pakistan, we delineated a critical region of 18.53 Mb on Chromosome 1p21.3-1p13.1. This region contains the gene encoding HsSAS-6, a centrosomal protein primordial for seeding the formation of new centrioles during the cell cycle. Both next-generation and Sanger sequencing revealed a homozygous c.185T>C missense mutation in the HsSAS-6 gene, resulting in a p.Ile62Thr substitution within a highly conserved region of the PISA domain of HsSAS-6. This variant is neither present in any single-nucleotide polymorphism or exome sequencing databases nor in a Pakistani control cohort. Experiments in tissue culture cells revealed that the Ile62Thr mutant of HsSAS-6 is substantially less efficient than the wild-type protein in sustaining centriole formation. Together, our findings demonstrate a dramatic impact of the mutation p.Ile62Thr on HsSAS-6 function and add this component to the list of genes mutated in primary microcephaly.

  5. Consanguinity and fetal growth in Pakistani Moslems.

    PubMed

    Honeyman, M M; Bahl, L; Marshall, T; Wharton, B A

    1987-03-01

    There is conflicting evidence about the effect of parental consanguinity on fetal growth. Previous studies have not always allowed for other factors that are known to affect birth weight, in particular, gestational age, parity, and maternal height. We have therefore studied this question in the Pakistani Moslem population in Birmingham. Babies born to parents who were first cousins were on average 80 g lighter than those born to unrelated parents, but this difference was not significant for the size of the sample studied. Nor were there any differences in the other measurements of the babies. After expressing birth weight in terms of centiles for gestational age, sex, parity, and maternal height, however, while there was no difference in the overall distribution of centiles, there were more poorly grown babies--that is, weight below the 10th centile--in the first cousin group. We conclude that parental consanguinity is associated with an increase in the number of poorly grown babies but that the overall effect on mean birth weight is small. PMID:3566315

  6. The frequency of consanguineous marriage among British Pakistanis.

    PubMed

    Darr, A; Modell, B

    1988-03-01

    An enquiry answered by 100 randomly selected British Pakistani mothers in the postnatal wards of two hospitals in West Yorkshire showed that 55 were married to their first cousins, while in only 33 cases had their mother been married to her first cousin. This suggests an increasing rate of consanguineous marriage in this relatively small group, by contrast with the decreasing rate observed in some other countries. The genetic implications merit further study. PMID:3351906

  7. In silico analysis of a disease-causing mutation in PCDH15 gene in a consanguineous Pakistani family with Usher phenotype

    PubMed Central

    Saleha, Shamim; Ajmal, Muhammad; Jamil, Muhammad; Nasir, Muhammad; Hameed, Abdul

    2016-01-01

    AIM To map Usher phenotype in a consanguineous Pakistani family and identify disease-associated mutation in a causative gene to establish phenotype-genotype correlation. METHODS A consanguineous Pakistani family in which Usher phenotype was segregating as an autosomal recessive trait was ascertained. On the basis of results of clinical investigations of affected members of this family disease was diagnosed as Usher syndrome (USH). To identify the locus responsible for the Usher phenotype in this family, genomic DNA from blood sample of each individual was genotyped using microsatellite Short Tandem Repeat (STR) markers for the known Usher syndrome loci. Then direct sequencing was performed to find out disease associated mutations in the candidate gene. RESULTS By genetic linkage analysis, the USH phenotype of this family was mapped to PCDH15 locus on chromosome 10q21.1. Three different point mutations in exon 11 of PCDH15 were identified and one of them, c.1304A>C was found to be segregating with the disease phenotype in Pakistani family with Usher phenotype. This, c.1304A>C transversion mutation predicts an amino-acid substitution of aspartic acid with an alanine at residue number 435 (p.D435A) of its protein product. Moreover, in silico analysis revealed conservation of aspartic acid at position 435 and predicated this change as pathogenic. CONCLUSION The identification of c.1304A>C pathogenic mutation in PCDH15 gene and its association with Usher syndrome in a consanguineous Pakistani family is the first example of a missense mutation of PCDH15 causing USH1 phenotype. In previous reports, it was hypothesized that severe mutations such as truncated protein of PCDH15 led to the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment. PMID:27275418

  8. Gene mapping in an anophthalmic pedigree of a consanguineous Pakistani family opened new horizons for research

    PubMed Central

    Ajmal, M; Zafar, S; Hameed, A

    2016-01-01

    ABSTRACT Clinical anophthalmia is a rare inherited disease of the eye and phenotype refers to the absence of ocular tissue in the orbit of eye. Patients may have unilateral or bilateral anophthalmia, and generally have short palpebral fissures and small orbits. Anophthalmia may be isolated or associated with a broader syndrome and may have genetic or environmental causes. However, genetic cause has been defined in only a small proportion of cases, therefore, a consanguineous Pakistani family of the Pashtoon ethnic group, with isolated clinical anophthalmia was investigated using linkage mapping. A family pedigree was created to trace the possible mode of inheritance of the disease. Blood samples were collected from affected as well as normal members of this family, and screened for disease-associated mutations. This family was analyzed for linkage to all the known loci of clinical anophthalmia, using microsatellite short tandem repeat (STR) markers. Direct sequencing was performed to find out disease-associated mutations in the candidate gene. This family with isolated clinical anophthalmia, was mapped to the SOX2 gene that is located at chromosome 3q26.3-q27. However, on exonic and regulatory regions mutation screening of the SOX2 gene, the disease-associated mutation was not identified. It showed that another gene responsible for development of the eye might be present at chromosome 3q26.3-q27 and needs to be identified and screened for the disease-associated mutation in this family. PMID:27785411

  9. Novel CYP1B1 mutations in consanguineous Pakistani families with primary congenital glaucoma

    PubMed Central

    Firasat, Sabika; Khan, Shaheen N.

    2008-01-01

    Purpose To identify the disease-causing mutations in three consanguineous Pakistani families with multiple members affected by primary congenital glaucoma. Methods Blood samples were collected, and DNA was extracted. Linkage analysis for reported primary congenital glaucoma loci was performed using closely spaced polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. All coding exons, the exon-intron boundaries, and the 5′ untranslated region of CYP1B1 were sequenced. Results The alleles of chromosome 2p markers segregate with the disease phenotype in all three families with positive LOD scores. The sequencing results identified three novel mutations (L177R, L487P, and D374E) and one previously reported mutation (E229K) in CYP1B1 that segregate with the disease phenotype in their respective families. None of these sequence variations were present in 96 ethnically matched control samples. Conclusions These results strongly suggest that missense mutations in CYP1B1 are most likely to be responsible for primary congenital glaucoma in these families. PMID:18989382

  10. Homozygous p.G61E mutation in a consanguineous Pakistani family with co-existence of juvenile-onset open angle glaucoma and primary congenital glaucoma.

    PubMed

    Bashir, Rasheeda; Tahir, Hafsa; Yousaf, Khazeema; Naz, Shagufta; Naz, Sadaf

    2015-10-10

    Glaucoma is one of the primary causes of visual impairment and blindness in the world. It is characterized by the damage to the optic nerve head and visual field loss. Variants in CYP1B1 are the most common cause of glaucoma in different world populations. We studied a consanguineous Pakistani family in which three affected individuals had a severe form of glaucoma with members in one generation diagnosed with juvenile-onset open angle glaucoma at 27 years of age, while the members of the next generation were affected with primary congenital glaucoma with onset at birth. Sequencing of CYP1B1 revealed a homozygous transition variant, c.182G>A, p.G61E which co-segregated with the disease phenotype. This variant has been previously reported to cause both recessively and dominantly inherited PCG and JOAG in different populations. However, this reported for the first time in Pakistani PCG and JOAG patients in a homozygous state. This is also the first ever report of a CYP1B1 variant segregating in a consanguineous family with co-existence of JOAG and PCG in two subsequent generations. This observation of different phenotypes due to an identical mutation suggests that primary congenital glaucoma and juvenile-onset open angle glaucoma can both be caused by homozygosity for the same mutation. It also indicates the reduced penetrance of the variant in those affected due to p.G61E mutation and further implies that modifiers have a role in controlling the time of onset of the disorder.

  11. Novel homozygous mutations in the EVC and EVC2 genes in two consanguineous families segregating autosomal recessive Ellis-van Creveld syndrome.

    PubMed

    Aziz, Abdul; Raza, Syed I; Ali, Salman; Ahmad, Wasim

    2016-01-01

    Ellis-van Creveld syndrome (EVC) is a rare developmental disorder characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails, teeth, oral and cardiac abnormalities. It is caused by biallelic mutations in the EVC or EVC2 gene, separated by 2.6 kb of genomic sequence on chromosome 4p16. In the present study, we have investigated two consanguineous families of Pakistani origin, segregating EVC in autosomal recessive manner. Linkage in the families was established to chromosome 4p16. Subsequently, sequence analysis identified a novel nonsense mutation (p.Trp234*) in exon 8 of the EVC2 gene and 15 bp duplication in exon 14 of the EVC gene in the two families. This further expands the mutations in the EVC or EVC2 genes resulting in the EVC syndrome.

  12. Autosomal recessive congenital cataract, intellectual disability phenotype linked to STX3 in a consanguineous Tunisian family.

    PubMed

    Chograni, M; Alkuraya, F S; Ourteni, I; Maazoul, F; Lariani, I; Chaabouni, H B

    2015-09-01

    The aim of this study is to investigate the genetic basis of autosomal recessive congenital cataract and intellectual disability phenotype in a consanguineous Tunisian family. The whole genome scan of the studied family was performed with single nucleotide polymorphisms (SNPs). The resulted runs of homozygosity (ROH) were analyzed through the integrated Systems Tool for Eye gene discovery (iSyTE) in order to prioritize candidate genes associated with congenital cataract. Selected genes were amplified and sequenced. Bioinformatic analysis was conducted to predict the function of the mutant gene. We identified a new specific lens gene named syntaxin 3 linked to the studied phenotype. The direct sequencing of this gene revealed a novel missense mutation c.122A>G which results in p.E41G. Bioinformatic analysis suggested a deleterious effect of this mutation on protein structure and function. Here, we report for the first time a missense mutation of a novel lens specific gene STX3 in a phenotype associating autosomal recessive congenital cataract and intellectual disability.

  13. Inhabitual autosomal recessive form of dentin dysplasia type I in a large consanguineous Moroccan family.

    PubMed

    Cherkaoui Jaouad, I; El Alloussi, M; Laarabi, F Z; Bouhouche, A; Ameziane, R; Sefiani, A

    2013-08-01

    Dentin dysplasia is a rare autosomal dominant genetic disease characterized by defect of dentin development and the causal gene is DSPP (Dentin Sialophosphoprotein gene). We report in the present study a large Moroccan family in which dentin dysplasia is clearly transmitted as an autosomal recessive trait. Four males and females family members born from healthy consanguineous parents are carriers of the typical features of the dentin dysplasia type I. Polymorphic markers that span the DSPP gene, allowed us to show that this locus is not linked to dentin dysplasia in our family. We also excluded in our family the SMOC2 gene (Sparc Related Modular Calcium Binding Protein 2) which was recently identified as a causal gene in dentin dysplasia type I with microdontia and misshapen teeth. This family represents, a new description of autosomal recessive pattern of inheritance of dentin dysplasia type I. Moreover, this form of dentin dysplasia is not allelic to the autosomal dominant dentin dysplasia and the genetic cause is to be discovered.

  14. Truncation of the E3 ubiquitin ligase component FBXO31 causes non-syndromic autosomal recessive intellectual disability in a Pakistani family.

    PubMed

    Mir, Asif; Sritharan, Kumudesh; Mittal, Kirti; Vasli, Nasim; Araujo, Carolina; Jamil, Talal; Rafiq, Muhammad Arshad; Anwar, Zubair; Mikhailov, Anna; Rauf, Sobiah; Mahmood, Huda; Shakoor, Abdul; Ali, Sabir; So, Joyce; Naeem, Farooq; Ayub, Muhammad; Vincent, John B

    2014-08-01

    In this study, we have performed autozygosity mapping on a large consanguineous Pakistani family segregating with intellectual disability. We identified two large regions of homozygosity-by-descent (HBD) on 16q12.2-q21 and 16q24.1-q24.3. Whole exome sequencing (WES) was performed on an affected individual from the family, but initially, no obvious mutation was detected. However, three genes within the HBD regions that were not fully captured during the WES were Sanger sequenced and we identified a five base pair deletion (actually six base pairs deleted plus one base pair inserted) in exon 7 of the gene FBXO31. The variant segregated completely in the family, in recessive fashion giving a LOD score of 3.95. This variant leads to a frameshift and a premature stop codon and truncation of the FBXO31 protein, p.(Cys283Asnfs*81). Quantification of mRNA and protein expression suggests that nonsense-mediated mRNA decay also contributes to the loss of FBXO31 protein in affected individuals. FBXO31 functions as a centrosomal E3 ubiquitin ligase, in association with SKP1 and Cullin-1, involved in ubiquitination of proteins targeted for degradation. The FBXO31/SKP1/Cullin1 complex is important for neuronal morphogenesis and axonal identity. FBXO31 also plays a role in dendrite growth and neuronal migration in developing cerebellar cortex. Our finding adds further evidence of the involvement of disruption of the protein ubiquitination pathway in intellectual disability.

  15. A homozygous mutation in a consanguineous family consolidates the role of ALDH1A3 in autosomal recessive microphthalmia.

    PubMed

    Roos, L; Fang, M; Dali, C; Jensen, H; Christoffersen, N; Wu, B; Zhang, J; Xu, R; Harris, P; Xu, X; Grønskov, K; Tümer, Z

    2014-09-01

    Anomalies of eye development can lead to the rare eye malformations microphthalmia and anophthalmia (small or absent ocular globes), which are genetically very heterogeneous. Several genes have been associated with microphthalmia and anophthalmia, and exome sequencing has contributed to the identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations.

  16. Identification of two novel mutations in CDHR1 in consanguineous Spanish families with autosomal recessive retinal dystrophy

    PubMed Central

    Nikopoulos, Konstantinos; Avila-Fernandez, Almudena; Corton, Marta; Lopez-Molina, Maria Isabel; Perez-Carro, Raquel; Bontadelli, Lara; Di Gioia, Silvio Alessandro; Zurita, Olga; Garcia-Sandoval, Blanca; Rivolta, Carlo; Ayuso, Carmen

    2015-01-01

    Inherited retinal dystrophies present extensive phenotypic and genetic heterogeneity, posing a challenge for patients’ molecular and clinical diagnoses. In this study, we wanted to clinically characterize and investigate the molecular etiology of an atypical form of autosomal recessive retinal dystrophy in two consanguineous Spanish families. Affected members of the respective families exhibited an array of clinical features including reduced visual acuity, photophobia, defective color vision, reduced or absent ERG responses, macular atrophy and pigmentary deposits in the peripheral retina. Genetic investigation included autozygosity mapping coupled with exome sequencing in the first family, whereas autozygome-guided candidate gene screening was performed by means of Sanger DNA sequencing in the second family. Our approach revealed nucleotide changes in CDHR1; a homozygous missense variant (c.1720C > G, p.P574A) and a homozygous single base transition (c.1485 + 2T > C) affecting the canonical 5’ splice site of intron 13, respectively. Both changes co-segregated with the disease and were absent among cohorts of unrelated control individuals. To date, only five mutations in CDHR1 have been identified, all resulting in premature stop codons leading to mRNA nonsense mediated decay. Our work reports two previously unidentified homozygous mutations in CDHR1 further expanding the mutational spectrum of this gene. PMID:26350383

  17. Genetic heterogeneity in Pakistani microcephaly families.

    PubMed

    Sajid Hussain, M; Marriam Bakhtiar, S; Farooq, M; Anjum, I; Janzen, E; Reza Toliat, M; Eiberg, H; Kjaer, K W; Tommerup, N; Noegel, A A; Nürnberg, P; Baig, S M; Hansen, L

    2013-05-01

    Autosomal recessive primary microcephaly (MCPH) is caused by mutations in at least eight different genes involved either in cell division or DNA repair. Most mutations are identified in consanguine families from Pakistan, Iran and India. To further assess their genetic heterogeneity and mutational spectra, we have analyzed 57 consanguine Pakistani MCPH families. In 34 MCPH families, we detected linkage to five out of the eight well-characterized disease loci and identified mutations in 27 families, leaving seven families without mutations in the coding exons of the presumably underlying MCPH genes. In the MCPH cohort 23 families could not be linked to any of the known loci, pointing to remarkable locus heterogeneity. The majority of mutations were found in ASPM followed by WDR62, CENPJ, CEP152 and MCPH1. One ASPM mutation (p.Trp1326*) was found in as many as eight families suggesting a Pakistani founder mutation. One third of the families were linked to ASPM followed by WDR62 confirming previous data. We identified three novel ASPM mutations, four novel WDR62 mutations, one novel MCPH1 mutation and two novel CEP152 mutations. CEP152 mutations have not been described before in the Pakistani population.

  18. A novel splice site mutation of CDHR1 in a consanguineous Israeli Christian Arab family segregating autosomal recessive cone-rod dystrophy

    PubMed Central

    Cohen, Ben; Chervinsky, Elena; Jabaly-Habib, Haneen; Shalev, Stavit A.; Briscoe, Daniel

    2012-01-01

    Purpose To investigate the genetic basis for autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. Methods Patients underwent a detailed ophthalmic examination, including funduscopy, electroretinography (ERG), visual field testing, and optical coherence tomography. Genome-wide homozygosity mapping using a single nucleotide polymorphism array was performed to identify homozygous regions shared between the two affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico analysis was used to predict the effect of the mutation on splicing. Results The family included two affected individuals. Clinical findings included progressive deterioration of visual acuity, photophobia, defective color vision, loss of central visual fields, pigmentary deposits localized mainly in the peripheral retina, a thinned and atrophic macular region, retinal vessel attenuation, absent ERG cone responses, and reduced ERG rod responses. Homozygosity mapping revealed several homozygous intervals shared among the affected individuals. One, a 12Mb interval on chromosome 10, included the CDHR1 gene. Direct sequencing revealed a single base transversion, c.1485+2T>G, located in the conserved donor splice site of Intron 13. This mutation cosegregated with the disease in the family, and was not detected in 208 Israeli Christian Arab control chromosomes. In silico analysis predicted that this mutation eliminates the Intron 13 donor splice site. Conclusions Only three distinct pathogenic mutations of CDHR1 have been reported to date in patients with autosomal recessive retinal degeneration. Here we report a novel splice site mutation of CDHR1, c.1485+2T>G, underlying autosomal recessive cone-rod dystrophy in a consanguineous Israeli Christian Arab family. This report expands the spectrum of pathogenic mutations of the CDHR1 gene. PMID:23233793

  19. A new locus on chromosome 22q13.31 linked to recessive genetic epilepsy with febrile seizures plus (GEFS+) in a Tunisian consanguineous family

    PubMed Central

    2013-01-01

    Background Genetic epilepsy with febrile seizures plus (GEFS+) is a familial epilepsy syndrome with extremely variable expressivity. The aim of our study was to identify the responsible locus for GEFS+ syndrome in a consanguineous Tunisian family showing three affected members, by carrying out a genome-wide single nucleotide polymorphisms (SNPs) genotyping followed by a whole-exome sequencing. We hypothesized an autosomal recessive (AR) mode of inheritance. Results Parametric linkage analysis and haplotype reconstruction identified a new unique identical by descent (IBD) interval of 527 kb, flanking by two microsatellite markers, 18GTchr22 and 15ACchr22b, on human chromosome 22q13.31 with a maximum multipoint LOD score of 2.51. Our analysis was refined by the use of a set of microsatellite markers. We showed that one of them was homozygous for the same allele in all affected individuals and heterozygous in healthy members of this family. This microsatellite marker, we called 17ACchr22, is located in an intronic region of TBC1D22A gene, which encodes a GTPase activator activity. Whole-exome sequencing did not reveal any mutation on chromosome 22q13.31 at the genome wide level. Conclusions Our findings suggest that TBC1D22A is a new locus for GEFS+. PMID:24067191

  20. [Consanguinity and congenital abnormalities].

    PubMed

    Søgaard, Marie; Vedsted-Jakobsen, Agnete

    2003-04-28

    Knowledge of consanguinity is relevant for employees in the Danish national health service, since about 7.5% of the Danish population has another ethnic background than Danish and the majority comes from cultures where consanguineous marriages are not unusual. In the literature it is found that consanguineous couples have a higher risk of having children with congenital malformations. The risk is increased by a factor 2 to 2 1/2. The average risk in Denmark is about 3%. Primarily, the autosomal recessive diseases are expressed in children with consanguineous parents. In order to advise and diagnose it is essential to clarify the consanguinity state. In case of pregnancy with consanguineous parents, we recommend: 1) Counselling to estimate the risk of foetal illness and information about possible examination possibilities. 2) An ultrasound scan at the gestational age of 11-14 weeks in order to measure nuchal translucency and an early malformation scan. 3) An ultrasound scan for malformations at the gestational age of 18-20 weeks. 4) An ultrasound scan especially in order to detect foetal heart malformations at the gestational age of 20-24 weeks.

  1. Consanguinity and reproductive health among Arabs.

    PubMed

    Tadmouri, Ghazi O; Nair, Pratibha; Obeid, Tasneem; Al Ali, Mahmoud T; Al Khaja, Najib; Hamamy, Hanan A

    2009-01-01

    Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity.

  2. Consanguinity and reproductive health among Arabs

    PubMed Central

    Tadmouri, Ghazi O; Nair, Pratibha; Obeid, Tasneem; Al Ali, Mahmoud T; Al Khaja, Najib; Hamamy, Hanan A

    2009-01-01

    Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically first cousin marriages which may reach 25-30% of all marriages. In some countries like Qatar, Yemen, and UAE, consanguinity rates are increasing in the current generation. Research among Arabs and worldwide has indicated that consanguinity could have an effect on some reproductive health parameters such as postnatal mortality and rates of congenital malformations. The association of consanguinity with other reproductive health parameters, such as fertility and fetal wastage, is controversial. The main impact of consanguinity, however, is an increase in the rate of homozygotes for autosomal recessive genetic disorders. Worldwide, known dominant disorders are more numerous than known recessive disorders. However, data on genetic disorders in Arab populations as extracted from the Catalogue of Transmission Genetics in Arabs (CTGA) database indicate a relative abundance of recessive disorders in the region that is clearly associated with the practice of consanguinity. PMID:19811666

  3. The effect of consanguinity on neonatal outcomes and health.

    PubMed

    Abbas, Hussein A; Yunis, Khalid

    2014-01-01

    Consanguineous marriages constitute a significant fraction of marriages worldwide and confer a major public health concern on newborns. In addition to the risk of acquiring a recessive genetic disease, the offspring of consanguineous parents are plausibly at an increased risk of preterm birth, decreased anthropometric measurements, congenital defects and mortality. How consanguinity confers such an increased risk is still largely unknown. In this review, we discuss the effect of consanguinity on selected gestational outcomes by delineating the different studies that have led to such findings. We also investigate the different conclusions that have emerged regarding the effect of consanguinity on gestational outcomes. PMID:25060272

  4. AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration

    PubMed Central

    Li, David; Jin, Chongfei; Jiao, Xiaodong; Li, Lin; Bushra, Tahmina; Naeem, Muhammad Asif; Butt, Nadeem H.; Husnain, Tayyab; Sieving, Paul A.; Riazuddin, Sheikh; Riazuddin, S. Amer

    2014-01-01

    Purpose To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Methods Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point linkage analysis was performed with the lod score method. Direct DNA sequencing of amplified genomic DNA was performed for mutation screening of candidate genes. Results Genome-wide linkage scans yielded a lod score of 3.05 at θ=0 for D17S1832 and 3.82 at θ=0 for D17S938, localizing the disease gene to a 12.22 cM (6.64 Mb) region flanked by D17S1828 and D17S1852 for family 61032 and family 61227, which contains aryl hydrocarbon receptor interacting protein-like 1 (AIPL1), a gene previously implicated in recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. Sequencing of AIPL1 showed a homozygous c.773G>C (p.Arg258Pro) sequence change in all affected individuals of family 61032 and a homozygous c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. Conclusions The results strongly suggest that the c.773G>C (p.R258P) and c.465G>T (p.(H93_Q155del)) mutations in AIPL1 cause autosomal recessive retinal degeneration in these consanguineous Pakistani families. PMID:24426771

  5. Autozygosity mapping of autosomal recessive non-syndromic sensorineural hearing loss (ARNSSNHL)

    SciTech Connect

    Brown, K.A.; Nobel, A.; Markham, A.F.

    1994-09-01

    Congenital deafness affects about 1 in 2000 persons and is of genetic origin in approximately half these cases. The majority of congenital deafness is non-syndromic and over 75% of cases are compatible with autosomal recessive inheritance. Mapping of the loci responsible for ARNSSNHL will be complicated by genetic heterogeneity. Our approach to isolating genes involved in ARNSSNHL is by autozygosity mapping which involves the genetic analysis of children resulting from consanguineous marriages with the aim of identifying regions of homozygosity unique to the genomes of affected individuals which have been inherited from a common ancestor. The population employed in this study is the Pakistani community of Leeds, Bradford and Manchester in the UK which originated from the Mirpur region of Pakistan. Microsatellite analysis of the genome with markers spaced, on average, 10 cM apart is in progress and the investigation of 15 consanguineous families has identified one family which shows linkage to human chromosome 13q. This family appears to be linked to the same autosomal recessive deafness locus as two Tunisian families recently described and confirms that this chromosome 13q locus is also responsible, although as a minor contributor, to the deafness observed in the Pakistani population.

  6. Consanguineous Iranian kindreds with severe Tourette syndrome.

    PubMed

    Motlagh, Maria G; Seddigh, Arshia; Dashti, Behnoosh; Leckman, James F; Alaghband-Rad, Javad

    2008-10-30

    The search for vulnerability genes for Tourette syndrome has been ongoing for nearly three decades. The contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. Homozygosity mapping has been successfully used to detect recessive loci within populations with high rates of consanguinity. Using this technique, even quite small inbred families can be informative due to autozygosity in which the two alleles at an autosomal locus are identical by descent (i.e., copies of a single ancestral gene). To explore the utility of this approach, we identified 12 consanguineous Iranian families. Remarkably, these families were seen with an unusual natural history characterized by the early onset of vocal tics and coprolalia and frequent comorbidity with obsessive-compulsive disorder. Genotyping the affected and unaffected members of these pedigrees has the potential to identify rare recessive contributions to this disorder.

  7. The first case of CDK5RAP2-related primary microcephaly in a non-consanguineous patient identified by next generation sequencing.

    PubMed

    Tan, Christopher A; Topper, Scott; Ward Melver, Catherine; Stein, Jennifer; Reeder, Amanda; Arndt, Kelly; Das, Soma

    2014-04-01

    Primary autosomal recessive microcephaly (MCPH) is a genetically heterogeneous condition characterized by congenital microcephaly and intellectual disability. To date, 10 MCPH loci have been identified and due to the genetic heterogeneity of this condition, molecular testing for MCPH can be complicated. Our methods involved employing a next generation sequencing panel of MCPH-related genes allowing for the evaluation of multiple disease loci simultaneously. Next generation sequencing analysis of a 6 year old female with primary microcephaly identified novel compound heterozygous mutations (c.524_528del and c.4005-1G>A) in the CDK5RAP2 gene. A review of the published literature to date reveals that only three mutations have been previously reported in the CDK5RAP2 gene in the homozygous state in three Northern Pakistani and one Somali consanguineous MCPH families. Our patient represents the first non-consanguineous Caucasian individual to have been identified with CDK5RAP2-related MCPH. As only a handful of patients have been reported in the literature with CDK5RAP2-related MCPH, we anticipate the identification of individuals with CDK5RAP2 mutations from all ethnic backgrounds will continue. Our patient contributes to the ethnic and genotypic spectrum of CDK5RAP2-related MCPH and supports the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations. Our results also highlight the utility of multi-gene sequencing panels to elucidate the etiology of genetically heterogeneous conditions. PMID:23726037

  8. Homozygosity mapping reveals novel and known mutations in Pakistani families with inherited retinal dystrophies

    PubMed Central

    Saqib, Muhammad Arif Nadeem; Nikopoulos, Konstantinos; Ullah, Ehsan; Sher Khan, Falak; Iqbal, Jamila; Bibi, Rabia; Jarral, Afeefa; Sajid, Sundus; Nishiguchi, Koji M.; Venturini, Giulia; Ansar, Muhammad; Rivolta, Carlo

    2015-01-01

    Inherited retinal dystrophies are phenotypically and genetically heterogeneous. This extensive heterogeneity poses a challenge when performing molecular diagnosis of patients, especially in developing countries. In this study, we applied homozygosity mapping as a tool to reduce the complexity given by genetic heterogeneity and identify disease-causing variants in consanguineous Pakistani pedigrees. DNA samples from eight families with autosomal recessive retinal dystrophies were subjected to genome wide homozygosity mapping (seven by SNP arrays and one by STR markers) and genes comprised within the detected homozygous regions were analyzed by Sanger sequencing. All families displayed consistent autozygous genomic regions. Sequence analysis of candidate genes identified four previously-reported mutations in CNGB3, CNGA3, RHO, and PDE6A, as well as three novel mutations: c.2656C > T (p.L886F) in RPGRIP1, c.991G > C (p.G331R) in CNGA3, and c.413-1G > A (IVS6-1G > A) in CNGB1. This latter mutation impacted pre-mRNA splicing of CNGB1 by creating a -1 frameshift leading to a premature termination codon. In addition to better delineating the genetic landscape of inherited retinal dystrophies in Pakistan, our data confirm that combining homozygosity mapping and candidate gene sequencing is a powerful approach for mutation identification in populations where consanguineous unions are common. PMID:25943428

  9. Association studies in consanguineous populations

    SciTech Connect

    Genin, E.; Clerget-Darpous, F.

    1996-04-01

    To study the genetic determinism of multifactorial diseases in large panmictic populations, a strategy consists in looking for an association with markers closely linked to candidate genes. A distribution of marker genotypes different in patients and controls may indicate that the candidate gene is involved in the disease. In panmictic populations, the power to detect the role of a candidate gene depends on the gametic disequilibrium with the marker locus. In consanguineous populations, we show that it depends on the inbreeding coefficient F as well. Inbreeding increases the power to detect the role of a recessive or quasi-recessive disease-susceptibility factor. The gain in power turns out to be greater for small values of the gametic disequilibrium. Moreover, even in the absence of gametic disequilibrium, the presence of inbreeding may allow to detect the role of a recessive factor. Ignoring inbreeding when it exists may lead to reject falsely a recessive model if the mode of inheritance is inferred on the distribution of genotypes among patients. 5 refs., 6 figs., 1 tab.

  10. Reflections on the consanguinity and birth outcome debate.

    PubMed

    Ahmad, W I

    1994-12-01

    The high rate of consanguineous marriages has been implicated as an important factor in the high rates of perinatal mortality and congenital malformations among the UK Pakistani population. This paper critically considers the debate on consanguinity and birth outcome. A critical review of epidemiological literature is placed in the context of wider, but centrally important, debates on social class and ethnic categorizations, notions of culture and literature on racism. The epidemiological literature is inconsistent in its findings, and is often based on data and arguments of dubious validity. Equally, notions of social class, ethnicity and culture used in such studies lack sophistication and require reconsideration. Health policy options based on promoting cultural change in marriage patterns, conveniently but unjustifiably, shift the blame of poor birth outcome onto the Pakistani community and are doomed to failure. The consanguinity hypothesis is over-simplistic to explain the higher rates of perinatal mortality and congenital malformations among the Pakistani population. Its popularity rests less on its scientific merit and more on its convenience in shifting the blame onto supposedly deviant cultures and marriage patterns and its fit with racist ideas of alienness and deviance. PMID:7880573

  11. Reflections on the consanguinity and birth outcome debate.

    PubMed

    Ahmad, W I

    1994-12-01

    The high rate of consanguineous marriages has been implicated as an important factor in the high rates of perinatal mortality and congenital malformations among the UK Pakistani population. This paper critically considers the debate on consanguinity and birth outcome. A critical review of epidemiological literature is placed in the context of wider, but centrally important, debates on social class and ethnic categorizations, notions of culture and literature on racism. The epidemiological literature is inconsistent in its findings, and is often based on data and arguments of dubious validity. Equally, notions of social class, ethnicity and culture used in such studies lack sophistication and require reconsideration. Health policy options based on promoting cultural change in marriage patterns, conveniently but unjustifiably, shift the blame of poor birth outcome onto the Pakistani community and are doomed to failure. The consanguinity hypothesis is over-simplistic to explain the higher rates of perinatal mortality and congenital malformations among the Pakistani population. Its popularity rests less on its scientific merit and more on its convenience in shifting the blame onto supposedly deviant cultures and marriage patterns and its fit with racist ideas of alienness and deviance.

  12. Consanguineous marriage in Iran.

    PubMed

    Saadat, M; Ansari-Lari, M; Farhud, D D

    2004-01-01

    Consanguineous marriage is a major feature of family systems in south-west Asia. The aim of the present study was to determine the current prevalence and patterns of consanguinity in Iran as a means of assessing the associated requirement for genetic counselling services. Consanguinity was studied in 12 ethnic/religious populations, the Persians (Shi'a and Sunni), Kurds (Shi'a and Sunni), Lurs, Azaris, Baluchis, Zabolis, Turkamans, Bakhtiaris, Ghashghais and Arabs. A multi-stage sampling design was used with a representative total sample of 306 343 couples. The overall rate of consanguineous marriage was 38.6% with a mean inbreeding coefficient (alpha) of 0.0185. First cousin marriages (27.9%) were the most common form of consanguineous union, with parallel patrilateral marriage especially favoured. Statistically significant differences were observed in the prevalence and patterns of consanguinity between ethnic/religious populations and geographical regions. There also were significant differences for proportions of consanguineous marriages between Shi'a and Sunni populations within the same ethnic group. The highest rates of consanguineous union were in the least affluent sections of the population. PMID:15204368

  13. Consanguineous marriage in Iran.

    PubMed

    Saadat, M; Ansari-Lari, M; Farhud, D D

    2004-01-01

    Consanguineous marriage is a major feature of family systems in south-west Asia. The aim of the present study was to determine the current prevalence and patterns of consanguinity in Iran as a means of assessing the associated requirement for genetic counselling services. Consanguinity was studied in 12 ethnic/religious populations, the Persians (Shi'a and Sunni), Kurds (Shi'a and Sunni), Lurs, Azaris, Baluchis, Zabolis, Turkamans, Bakhtiaris, Ghashghais and Arabs. A multi-stage sampling design was used with a representative total sample of 306 343 couples. The overall rate of consanguineous marriage was 38.6% with a mean inbreeding coefficient (alpha) of 0.0185. First cousin marriages (27.9%) were the most common form of consanguineous union, with parallel patrilateral marriage especially favoured. Statistically significant differences were observed in the prevalence and patterns of consanguinity between ethnic/religious populations and geographical regions. There also were significant differences for proportions of consanguineous marriages between Shi'a and Sunni populations within the same ethnic group. The highest rates of consanguineous union were in the least affluent sections of the population.

  14. Genetics of consanguineous marriage: Impact and importance of counseling.

    PubMed

    Akrami, Seyed Mohammad

    2012-12-01

    Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage.

  15. Genetics of consanguineous marriage: Impact and importance of counseling

    PubMed Central

    Akrami, Seyed Mohammad

    2012-01-01

    Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage.

  16. Science and society: genetic counselling and customary consanguineous marriage.

    PubMed

    Modell, Bernadette; Darr, Aamra

    2002-03-01

    Consanguineous marriage is customary in many societies, but leads to an increased birth prevalence of infants with severe recessive disorders. It is therefore often proposed that consanguineous marriage should be discouraged on medical grounds. However, several expert groups have pointed out that this proposal is inconsistent with the ethical principles of genetic counselling, overlooks the social importance of consanguineous marriage and is ineffective. Instead, they suggest that the custom increases the possibilities for effective genetic counselling, and recommend a concerted effort to identify families at increased risk, and to provide them with risk information and carrier testing when feasible.

  17. Consanguinity and dysmorphology in Arabs.

    PubMed

    Al-Gazali, Lihadh; Hamamy, Hanan

    2014-01-01

    Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed.

  18. Identification of recurrent and novel mutations in TULP1 in Pakistani families with early-onset retinitis pigmentosa

    PubMed Central

    Ajmal, Muhammad; Khan, Muhammad Imran; Micheal, Shazia; Ahmed, Waqas; Shah, Ashfa; Venselaar, Hanka; Bokhari, Habib; Azam, Aisha; Waheed, Nadia Khalida; Collin, Rob W.J.; den Hollander, Anneke I.; Qamar, Raheel

    2012-01-01

    Purpose To identify the genetic defects underlying retinitis pigmentosa (RP) in Pakistani families. Methods Genome-wide high-density single-nucleotide-polymorphism microarray analysis was performed using the DNA of nine affected individuals from two large families with multiple consanguineous marriages. Data were analyzed to identify homozygous regions that are shared by affected sibs in each family. Sanger sequencing was performed for genes previously implicated in autosomal recessive RP and allied retinal dystrophies that resided in the identified homozygous regions. Probands from both families underwent fundus examination and electroretinogram measurements. Results The tubby-like protein 1 gene (TULP1) was present in the largest homozygous region in both families. Sequence analysis identified a previously reported mutation (c.1138A>G; p.Thr380Ala) in one family and a novel pathogenic variant (c.1445G>A; p.Arg482Gln) in the other family. Both variants were found to be present in a homozygous state in all affected individuals, were heterozygous present in the unaffected parents, and heterozygous present or absent in normal individuals. Affected individuals of both families showed an early-onset form of RP. Conclusions Homozygosity mapping, combined with candidate-gene analysis, successfully identified genetic defects in TULP1 in two large Pakistani families with early-onset retinitis pigmentosa. PMID:22665969

  19. Consanguineous marriage and its relevance to obstetric practice.

    PubMed

    de Costa, Caroline M

    2002-08-01

    At the beginning of the twenty-first century, consanguineous marriage is practiced widely in many parts of the world. More than 2 billion people, of various religious and ethnic backgrounds, live in countries where a large proportion of marriages are contracted between blood relatives. The practice is seen as promoting family stability and having significant social and economic advantages. Consanguineous marriage is important genetically-the children of consanguineous unions are more often homozygous for particular alleles than are the offspring of unrelated parents, and therefore, autosomal recessive disorders, which may be lethal or debilitating, are more common in such children. Health-care providers working with communities where consanguineous marriage is common, in particular obstetricians, family physicians, and pediatricians, need to be aware of the possible impact of such marriages on pregnancy outcomes, so the best possible genetic and antenatal care can be provided, sympathetically and nonjudgmentally, and the best possible results obtained.

  20. Consanguineous marriages in Afghanistan.

    PubMed

    Saify, Khyber; Saadat, Mostafa

    2012-01-01

    The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Afghanistan populations. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 7140 from the following provinces: Badakhshan, Baghlan, Balkh, Bamyan, Kabul, Kunduz, Samangan and Takhar. Consanguineous marriages were classified by the degree of relationship between couples: double first cousins, first cousins, first cousins once removed, second cousins and beyond second cousins. The coefficient of inbreeding (F) was calculated for each couple and the mean coefficient of inbreeding (α) estimated for each population. The proportion of consanguineous marriages in the country was 46.2%, ranging from 38.2% in Kabul province to 51.2% in Bamyan province. The equivalent mean inbreeding coefficient (α) was 0.0277, and ranged from 0.0221 to 0.0293 in these two regions. There were significant differences between provinces for frequencies of different types of marriages (p<0.001). First cousin marriages (27.8%) were the most common type of consanguineous marriages, followed by double first cousin (6.9%), second cousin (5.8%), beyond second cousin (3.9%) and first cousin once removed (1.8%). There were significant differences between ethnic groups for the types of marriages (χ2=177.6, df=25, p<0.001). Tajiks (Soni) and Turkmens (also Pashtuns) showed the lowest (α=0.0250) and highest (α=0.0297) mean inbreeding coefficients, respectively, among the ethnic groups in Afghanistan. The study shows that Afghanistan's populations, like other Islamic populations, have a high level of consanguinity.

  1. Autosomal recessive epidermolytic palmoplantar keratoderma.

    PubMed

    Alsaleh, Q A; Teebi, A S

    1990-08-01

    Palmoplantar keratoderma (PPK) is a heterogeneous group of disorders. Epidermolytic PPK is a well delineated autosomal dominant entity, but no recessive form is known. Here we report two sons of phenotypically normal, consanguineous, Arab parents with features suggestive of PPK. They presented with patchy eczematous skin lesions followed by PPK and raised serum levels of IgE. Skin biopsy from the keratotic lesions showed the features of epidermolytic hyperkeratosis. Autosomal recessive inheritance is suggested and the differential diagnosis is discussed.

  2. Specific aspects of consanguinity: some examples from the Tunisian population.

    PubMed

    Romdhane, Lilia; Ben Halim, Nizar; Rejeb, Insaf; Kefi, Rym; Bouyacoub, Yosra; Ben Rekaya, Mariem; Messai, Habib; Messaoud, Olfa; Riahi, Zied; Bonnet, Crystel; Ben Rhouma, Faten; Nagara, Majdi; Petit, Christine; McElreavey, Ken; Romeo, Giovanni; Abdelhak, Sonia

    2014-01-01

    Located at the cross-road between Europe and Africa, Tunisia is a North African country of 11 million inhabitants. Throughout its history, it has been invaded by different ethnic groups. These historical events, and consanguinity, have impacted on the spectrum and frequency of genetic diseases in Tunisia. Investigations of Tunisian families have significantly contributed to elucidation of the genetic bases of rare disorders, providing an invaluable resource of cases due to particular familial structures (large family size, consanguinity and share of common ancestors). In the present study, we report on and review different aspects of consanguinity in the Tunisian population as a case study, representing several features common to neighboring or historically related countries in North Africa and the Middle East. Despite the educational, demographic and behavioral changes that have taken place during the last four decades, familial and geographical endogamy still exist at high frequencies, especially in rural areas. The health implications of consanguinity in Tunisian families include an increased risk of the expression of autosomal recessive diseases and particular phenotypic expressions. With new sequencing technologies, the investigation of consanguineous populations provides a unique opportunity to better evaluate the impact of consanguinity on the genome dynamic and on health, in addition to a better understanding of the genetic bases of diseases. PMID:25060280

  3. Genetics of consanguineous marriage: Impact and importance of counseling.

    PubMed

    Akrami, Seyed Mohammad

    2012-12-01

    Consanguineous marriage, marriage between close biological kin, especially that between first cousins, is socially favored in some parts of North Africa, the Middle East and Asia. An increased rate of congenital anomalies and autosomal recessive disorders are significantly associated with such practice. In such communities, misunderstanding and external attempts to discourage such marriage without proper genetic counseling seem to be inappropriate and unsuccessful. Update in knowledge of clinicians especially pediatricians is the aim of this paper regarding importance and issues behind consanguineous marriage. PMID:27625826

  4. Consanguineous marriages, pearls and perils: Geneva International Consanguinity Workshop Report.

    PubMed

    Hamamy, Hanan; Antonarakis, Stylianos E; Cavalli-Sforza, Luigi Luca; Temtamy, Samia; Romeo, Giovanni; Kate, Leo P Ten; Bennett, Robin L; Shaw, Alison; Megarbane, Andre; van Duijn, Cornelia; Bathija, Heli; Fokstuen, Siv; Engel, Eric; Zlotogora, Joel; Dermitzakis, Emmanouil; Bottani, Armand; Dahoun, Sophie; Morris, Michael A; Arsenault, Steve; Aglan, Mona S; Ajaz, Mubasshir; Alkalamchi, Ayad; Alnaqeb, Dhekra; Alwasiyah, Mohamed K; Anwer, Nawfal; Awwad, Rawan; Bonnefin, Melissa; Corry, Peter; Gwanmesia, Lorraine; Karbani, Gulshan A; Mostafavi, Maryam; Pippucci, Tommaso; Ranza-Boscardin, Emmanuelle; Reversade, Bruno; Sharif, Saghira M; Teeuw, Marieke E; Bittles, Alan H

    2011-09-01

    Approximately 1.1 billion people currently live in countries where consanguineous marriages are customary, and among them one in every three marriages is between cousins. Opinions diverge between those warning of the possible health risks to offspring and others who highlight the social benefits of consanguineous marriages. A consanguinity study group of international experts and counselors met at the Geneva International Consanguinity Workshop from May 3, 2010, to May 7, 2010, to discuss the known and presumptive risks and benefits of close kin marriages and to identify important future areas for research on consanguinity. The group highlighted the importance of evidence-based counseling recommendations for consanguineous marriages and of undertaking both genomic and social research in defining the various influences and outcomes of consanguinity. Technological advances in rapid high-throughput genome sequencing and for the identification of copy number variants by comparative genomic hybridization offer a significant opportunity to identify genotype-phenotype correlations focusing on autozygosity, the hallmark of consanguinity. The ongoing strong preferential culture of close kin marriages in many societies, and among migrant communities in Western countries, merits an equivalently detailed assessment of the social and genetic benefits of consanguinity in future studies.

  5. Consanguinity, human evolution, and complex diseases

    PubMed Central

    Bittles, A. H.; Black, M. L.

    2010-01-01

    There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F ≥ 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ≈3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates. PMID:19805052

  6. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2

    PubMed Central

    Santos-Cortez, Regie Lyn P.; Faridi, Rabia; Rehman, Atteeq U.; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J.; Isaacson, Rivka; Belyantseva, Inna A.; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A.; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-e-Huma; Smith, Joshua D.; Nickerson, Deborah A.; Bamshad, Michael J.; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B.; Leal, Suzanne M.

    2016-01-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2−/− mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2−/− mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  7. Autosomal-Recessive Hearing Impairment Due to Rare Missense Variants within S1PR2.

    PubMed

    Santos-Cortez, Regie Lyn P; Faridi, Rabia; Rehman, Atteeq U; Lee, Kwanghyuk; Ansar, Muhammad; Wang, Xin; Morell, Robert J; Isaacson, Rivka; Belyantseva, Inna A; Dai, Hang; Acharya, Anushree; Qaiser, Tanveer A; Muhammad, Dost; Ali, Rana Amjad; Shams, Sulaiman; Hassan, Muhammad Jawad; Shahzad, Shaheen; Raza, Syed Irfan; Bashir, Zil-E-Huma; Smith, Joshua D; Nickerson, Deborah A; Bamshad, Michael J; Riazuddin, Sheikh; Ahmad, Wasim; Friedman, Thomas B; Leal, Suzanne M

    2016-02-01

    The sphingosine-1-phosphate receptors (S1PRs) are a well-studied class of transmembrane G protein-coupled sphingolipid receptors that mediate multiple cellular processes. However, S1PRs have not been previously reported to be involved in the genetic etiology of human traits. S1PR2 lies within the autosomal-recessive nonsyndromic hearing impairment (ARNSHI) locus DFNB68 on 19p13.2. From exome sequence data we identified two pathogenic S1PR2 variants, c.323G>C (p.Arg108Pro) and c.419A>G (p.Tyr140Cys). Each of these variants co-segregates with congenital profound hearing impairment in consanguineous Pakistani families with maximum LOD scores of 6.4 for family DEM4154 and 3.3 for family PKDF1400. Neither S1PR2 missense variant was reported among ∼120,000 chromosomes in the Exome Aggregation Consortium database, in 76 unrelated Pakistani exomes, or in 720 Pakistani control chromosomes. Both DNA variants affect highly conserved residues of S1PR2 and are predicted to be damaging by multiple bioinformatics tools. Molecular modeling predicts that these variants affect binding of sphingosine-1-phosphate (p.Arg108Pro) and G protein docking (p.Tyr140Cys). In the previously reported S1pr2(-/-) mice, stria vascularis abnormalities, organ of Corti degeneration, and profound hearing loss were observed. Additionally, hair cell defects were seen in both knockout mice and morphant zebrafish. Family PKDF1400 presents with ARNSHI, which is consistent with the lack of gross malformations in S1pr2(-/-) mice, whereas family DEM4154 has lower limb malformations in addition to hearing loss. Our findings suggest the possibility of developing therapies against hair cell damage (e.g., from ototoxic drugs) through targeted stimulation of S1PR2. PMID:26805784

  8. Consanguineous marriage in Jordan.

    PubMed

    Khoury, S A; Massad, D

    1992-07-15

    We conducted a population-based study of consanguineous marriages in Jordan. About two thousand households were interviewed. First cousin marriages were encountered in 32.03%, second cousin in 6.8%, distant relation in 10.5%, and no relation in 50% of all marriages, respectively. Inbreeding coefficients were compared with those of other countries. The most important variables affecting inbreeding were social tradition, religion, education, and place of residence--urban vs. rural. Secular trends appear rather stable since the early decades of the twentieth century, especially for first cousin marriages. Jordan society showed a deeply rooted traditional behavioral pattern when inbreeding is considered.

  9. A new autosomal recessive non-progressive congenital cerebellar ataxia associated with mental retardation, optic atrophy, and skin abnormalities (CAMOS) maps to chromosome 15q24-q26 in a large consanguineous Lebanese Druze Family.

    PubMed

    Delague, Valérie; Bareil, Corinne; Bouvagnet, Patrice; Salem, Nabiha; Chouery, Eliane; Loiselet, Jacques; Mégarbané, André; Claustres, Mireille

    2002-03-01

    Congenital cerebellar ataxias are a heterogeneous group of non-progressive disorders characterized by hypotonia and developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We report the mapping of a disease gene in a large inbred Lebanese Druze family, with five cases of a new form of non-progressive autosomal recessive congenital ataxia associated with optic atrophy, severe mental retardation, and structural skin abnormalities, to a 3.6-cM interval on chromosome 15q24-15q26.

  10. Autosomal recessive epidermolytic palmoplantar keratoderma.

    PubMed Central

    Alsaleh, Q A; Teebi, A S

    1990-01-01

    Palmoplantar keratoderma (PPK) is a heterogeneous group of disorders. Epidermolytic PPK is a well delineated autosomal dominant entity, but no recessive form is known. Here we report two sons of phenotypically normal, consanguineous, Arab parents with features suggestive of PPK. They presented with patchy eczematous skin lesions followed by PPK and raised serum levels of IgE. Skin biopsy from the keratotic lesions showed the features of epidermolytic hyperkeratosis. Autosomal recessive inheritance is suggested and the differential diagnosis is discussed. Images PMID:2145438

  11. A Common Ancestral Mutation in CRYBB3 Identified in Multiple Consanguineous Families with Congenital Cataracts

    PubMed Central

    Irum, Bushra; Khan, Arif O.; Wang, Qiwei; Li, David; Khan, Asma A.; Husnain, Tayyab; Akram, Javed; Riazuddin, Sheikh

    2016-01-01

    Purpose This study was performed to investigate the genetic determinants of autosomal recessive congenital cataracts in large consanguineous families. Methods Affected individuals underwent a detailed ophthalmological examination and slit-lamp photographs of the cataractous lenses were obtained. An aliquot of blood was collected from all participating family members and genomic DNA was extracted from white blood cells. Initially, a genome-wide scan was performed with genomic DNAs of family PKCC025 followed by exclusion analysis of our familial cohort of congenital cataracts. Protein-coding exons of CRYBB1, CRYBB2, CRYBB3, and CRYBA4 were sequenced bidirectionally. A haplotype was constructed with SNPs flanking the causal mutation for affected individuals in all four families, while the probability that the four familial cases have a common founder was estimated using EM and CHM-based algorithms. The expression of Crybb3 in the developing murine lens was investigated using TaqMan assays. Results The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis localized the causal phenotype in family PKCC025 to chromosome 22q with statistically significant two-point logarithm of odds (LOD) scores. Subsequently, we localized three additional families, PKCC063, PKCC131, and PKCC168 to chromosome 22q. Bidirectional Sanger sequencing identified a missense variation: c.493G>C (p.Gly165Arg) in CRYBB3 that segregated with the disease phenotype in all four familial cases. This variation was not found in ethnically matched control chromosomes, the NHLBI exome variant server, or the 1000 Genomes or dbSNP databases. Interestingly, all four families harbor a unique disease haplotype that strongly suggests a common founder of the causal mutation (p<1.64E-10). We observed expression of Crybb3 in the mouse lens as early as embryonic day 15 (E15), and expression remained relatively steady throughout

  12. Initial expression of the Papillon-Lefèvre syndrome in consanguine family

    PubMed Central

    Singh, Anand Pratap; Chaitra, T R; Singh, Surendra Pratap; Kulkarni, Adwait Uday

    2012-01-01

    A rare case of Papillon-Lefevre syndrome is discussed with clinicoradiological presentation. The purpose of the case report is to make the medical community aware of this rare syndrome and its association with consanguinity. Papillon-Lefevre syndrome is an extremely rare genodermatosis of autosomal-recessive inheritance which usually manifests itself between the ages of 6 months to 4 years characterised by diffuse palmoplanter hyperkeratosis (keratoderma), and rapidly progressive and devastating periodontitis, affecting the primary as well as permanent dentition. Papillon-Lefevre syndrome results from a combination of host and bacterial factors, including recessive gene, consanguinity, specific periodontal pathogens and lack of thorough oral hygiene. The present case report describes Papillon-Lefevre syndrome and its association with consanguinity in a 3-year-old girl. PMID:22922917

  13. Effect of consanguinity among North India Muslims.

    PubMed

    Basu, S K

    1975-01-01

    Endogamous Muslim groups in Delhi and Lucknow, India, were studied to discover the effects of consanguineous marriage on fertility, mortality, and net-fertility rates. Sayyad Shias have a much higher frequency of parental consanguinity. Consanguineous marriages occurred among the following groups in descending order of frequency: Sheikh, Pathan, and Moghul Sumnis. Different forms of inbreeding occurred among the various groups. Most Muslims oppose family planning on religous grounds. In both Sayyad Shias and Sheikh Sumni consanguineous marriages there was a higher fertility rate than among non-consanguineous marriages. The net-fertility rate was not higher, because mortality before 21 was highest among first cousins. PMID:12307582

  14. Benign muscular dystrophy: risk calculation in families with consanguinity.

    PubMed Central

    Wolff, G; Müller, C R; Grimm, T

    1989-01-01

    This report concerns two families in which the index patients are sporadic cases of a benign form of muscular dystrophy. In both families the sisters of the patients have married a close relative. The respective risks for a child of these consanguineous marriages being affected with either X linked Becker muscular dystrophy or autosomal recessive limb girdle muscular dystrophy is calculated using pedigree information, results of serum creatine kinase determinations, and also, in one family, results of DNA typing using RFLPs from the short arm of the X chromosome. PMID:2732990

  15. A homozygous missense variant in type I keratin KRT25 causes autosomal recessive woolly hair

    PubMed Central

    Ansar, Muhammad; Raza, Syed Irfan; Lee, Kwanghyuk; Irfanullah; Shahi, Shamim; Acharya, Anushree; Dai, Hang; Smith, Joshua D; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Santos-Cortez, Regie Lyn P; Ahmad, Wasim; Leal, Suzanne M

    2016-01-01

    Background Woolly hair (WH) is a hair abnormality that is primarily characterised by tightly curled hair with abnormal growth. Methods In two unrelated consanguineous Pakistani families with non-syndromic autosomal recessive (AR) WH, homozygosity mapping and linkage analysis identified a locus within 17q21.1–q22, which contains the type I keratin gene cluster. A DNA sample from an affected individual from each family underwent exome sequencing. Results A homozygous missense variant c.950T>C (p.(Leu317Pro)) within KRT25 segregated with ARWH in both families, and has a combined maximum two-point LOD score of 7.9 at ϴ=0. The KRT25 variant is predicted to result in disruption of the second α-helical rod domain and the entire protein structure, thus possibly interfering with heterodimerisation of K25 with type II keratins within the inner root sheath (IRS) of the hair follicle and the medulla of the hair shaft. Conclusions Our findings implicate a novel gene involved in human hair abnormality, and are consistent with the curled, fragile hair found in mice with Krt25 mutations, and further support the role of IRS-specific type I keratins in hair follicle development and maintenance of hair texture. PMID:26160856

  16. Consanguineous marriages in the United Arab Emirates.

    PubMed

    al-Gazali, L I; Bener, A; Abdulrazzaq, Y M; Micallef, R; al-Khayat, A I; Gaber, T

    1997-10-01

    This study examines the frequency of consanguineous marriage and the coefficient of inbreeding in the United Arab Emirates (UAE). The study was conducted in Al Ain and Dubai cities between October 1994 and March 1995. A sample of 2033 married UAE females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (50.5%) with a coefficient of inbreeding of 0.0222. The commonest type of consanguineous marriage was between first cousins (26.2%). Double first cousin marriages were common (3.5%) compared to other populations. The consanguinity rate in the UAE has increased from 39% to 50.5% in one generation. The level of consanguinity was higher in Al Ain (54.2%) than in Dubai (40%).

  17. Late infantile autosomal recessive myotonia, mental retardation, and skeletal abnormalities: a new autosomal recessive syndrome.

    PubMed Central

    Richieri-Costa, A; Garcia da Silva, S M; Frota-Pessoa, O

    1984-01-01

    Four sibs of non-consanguineous parents who had myotonia from late infancy are described. Mild to moderate mental retardation, severe bone abnormalities of the vertebral column (mainly in the thoracolumbar region), and short stature were also observed. Autosomal recessive inheritance is demonstrated. These cases are compared with reported cases of the Schwartz-Jampel syndrome. Images PMID:6716408

  18. Congenital vocal cord paralysis with possible autosomal recessive inheritance: Case report and review of the literature

    SciTech Connect

    Koppel, R.; Friedman, S.; Fallet, S.

    1996-08-23

    We describe an infant with congenital vocal cord paralysis born to consanguineous parents. While autosomal dominant and X-linked inheritance have been previously reported in this condition, we conclude that the degree of parental consanguinity in this case strongly suggests autosomal recessive inheritance. Although we cannot exclude X-linked inheritance, evidence from animal studies demonstrates autosomal recessive inheritance and provides a possible molecular basis for congenital vocal cord paralysis. 14 refs., 1 fig.

  19. Consanguineous marriage among the Fulani.

    PubMed

    Hampshire, K R; Smith, M T

    2001-08-01

    The Fulani are a broad ethnic category of nomadic and seminomadic pastoralists and agropastoralists living in the semiarid Sahel region of sub-Saharan Africa. The Fulani are patrilineal, patrilocal, and moderately polygynous, with arranged first marriages accompanied by the payment of bridewealth, ideally in the form of cattle. Consanguineous marriage is frequent, with first or second cousin marriage preferred. In this paper we present data on levels of consanguineous marriage among the Fulani of northern Burkina Faso and test the hypothesis that inbreeding may be more frequent when there is a scarcity of cattle available, since bridewealth demands are thought to be reduced with close-kin marriage. Among 308 women's marriages, 203 (65.8%) were between kin up to and including second cousins, and 102 (33.1%) were between nonkin. Among 276 men's marriages, 196 (71.0%) were between kin up to and including second cousins, and 77 (27.9%) were between nonkin. The mean population inbreeding coefficient (alpha) was 0.0355 for women, and 0.0374 for men. No increase was found in population levels of inbreeding estimated from marriages contracted after the droughts of 1973 and 1984, which drastically reduced the Fulani's cattle stocks. However, a significantly higher rate of consanguineous marriage was found in families owning the fewest cattle.

  20. Prevalence of consanguineous marriages among Iranian Georgians.

    PubMed

    Rafiee, Laleh; Saadat, Mostafa

    2011-01-01

    Consanguineous marriage--marriage between relatives--has received a great deal of attention as a potential risk factor for many adverse health outcomes. The present cross-sectional study was done in order to illustrate the prevalence and types of consanguineous marriages among Iranian Georgians living in Frydoonshahr (Isfahan province, central Iran). Data on consanguineous marriages were collected using a simple questionnaire. The total number of couples in this study was 646. Consanguineous marriage was classified by the degree of relationship between couples. First cousin marriages (14.2%) were the most common type of consanguineous marriages, followed by second cousin (7.0%), beyond second cousin (1.5%) and first cousin once removed (0.6%). The mean inbreeding coefficient (α) was calculated as 0.0104 for the population. The present study shows that the study population, as other Iranian populations, has a high level of consanguinity.

  1. Autosomal Recessive Primary Microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum.

    PubMed

    Mahmood, Saqib; Ahmad, Wasim; Hassan, Muhammad J

    2011-01-01

    Autosomal Recessive Primary Microcephaly (MCPH) is a rare disorder of neurogenic mitosis characterized by reduced head circumference at birth with variable degree of mental retardation. In MCPH patients, brain size reduced to almost one-third of its original volume due to reduced number of generated cerebral cortical neurons during embryonic neurogensis. So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes (MCPH1, WDR62, CDK5RAP2, CEP152, ASPM, CENPJ, and STIL) identified from different world populations. Contribution of ASPM and WDR62 gene mutations in MCPH World wide is more than 50%. By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. Recent discoveries of mammalian models for MCPH have open up horizons for researchers to add more knowledge regarding the etiology and pathophysiology of MCPH. High incidence of MCPH in Pakistani population reflects the most probable involvement of consanguinity. Genetic counseling and clinical management through carrier detection/prenatal diagnosis in MCPH families can help reducing the incidence of this autosomal recessive disorder. PMID:21668957

  2. Consanguineous Marriage and Marital Adjustment in Turkey.

    ERIC Educational Resources Information Center

    Fisiloglu, Hurol

    2001-01-01

    Investigates the relationship between consanguineous marriage and marital adjustment in Turkey. The results of the study show that the consanguineous marriage group had significantly lower marital adjustment and had more conflict with extended family than the nonconsanguineous marriage group. The finding is discussed in the context of research and…

  3. Modernization and Consanguineous Marriage in Iran.

    ERIC Educational Resources Information Center

    Givens, Benjamin P.; Hirschman, Charles

    1994-01-01

    Used data on 4,667 women from the Iran Fertility Survey to examine trends and social correlates of consanguineous marriage. Found modest increase in proportion of marriages between cousins in Iran from 1940s to 1970s. Results suggest that modernization may be eroding social bases on consanguinity, whereas increased availability of cousins may lead…

  4. Autosomal recessive

    MedlinePlus

    ... and the other gene comes from the father. Recessive inheritance means both genes in a pair must be abnormal to cause ... born to parents who carry the same autosomal recessive change ... abnormal gene from both parents and developing the disease. You ...

  5. Consanguinity: A Risk Factor for Preterm Birth at Less Than 33 Weeks’ Gestation

    PubMed Central

    Mumtaz, Ghina; Nassar, Anwar H.; Mahfoud, Ziyad; El-Khamra, Akaber; Al-Choueiri, Nathalie; Adra, Abdallah; Murray, Jeffrey C.; Zalloua, Pierre; Yunis, Khalid A.

    2010-01-01

    Consanguinity promotes homozygosity of recessive susceptibility gene variants and can be used to investigate a recessive component in diseases whose inheritance is uncertain. The objective of this study was to assess the association between consanguinity and preterm birth (PTB), stratified by gestational age and clinical presentation (spontaneous vs. medically indicated). Data were collected on 39,745 singleton livebirths without major birth defects, admitted to 19 hospitals in Lebanon, from September 2003 to December 2007. Deliveries before completed 33 weeks’ gestation and deliveries at 33–36 weeks’ gestation were compared, with respect to cousin marriage, with those after completed 36 weeks’ gestation by using multinomial multiple logistic regression. Overall, infants of consanguineous parents had a statistically significant 1.6-fold net increased risk of being born at less than 33 weeks’ gestation compared with infants of unrelated parents. This association was statistically significant only with spontaneous PTB. There was no increased risk of being born at 33–36 weeks’ gestation associated with consanguinity for both clinical presentations of PTB. Our findings support a genetic contribution to early onset PTB and suggest that early PTB should be targeted in future genetic studies rather than the classic lumping of all births less than 37 weeks’ gestation. PMID:20978088

  6. Hirschsprung disease associated with polydactyly, unilateral renal agenesis, hypertelorism, and congenital deafness: a new autosomal recessive syndrome.

    PubMed Central

    Santos, H; Mateus, J; Leal, M J

    1988-01-01

    An association of Hirschsprung disease with polydactyly, unilateral renal agenesis, hypertelorism, and congenital deafness is described in sibs (brother and sister) of consanguineous parents. It is suggested that this might represent a new autosomal recessive syndrome. Images PMID:3351909

  7. Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society.

    PubMed

    Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien Ac; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

    2014-04-01

    Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling.

  8. Consanguineous marriage and reproductive risk: attitudes and understanding of ethnic groups practising consanguinity in Western society.

    PubMed

    Teeuw, Marieke E; Loukili, Ghariba; Bartels, Edien Ac; ten Kate, Leo P; Cornel, Martina C; Henneman, Lidewij

    2014-04-01

    Consanguineous couples should be adequately informed about their increased reproductive risk and possibilities for genetic counselling. Information may only be effective if it meets the needs of the target group. This study aimed to gain more insight into: (1) attitudes of people belonging to ethnic groups in Western society towards consanguinity and their understanding of risk for offspring; and (2) their attitudes regarding reproductive information targeted at consanguineous couples. Dutch Moroccans and Turks were invited to complete an online questionnaire by snowball sampling and by placing a link on two popular Dutch Moroccan/Turkish forum websites between September and October 2011. The questionnaire was completed by 201 individuals who were, on average, neither positive nor negative towards consanguinity. Respondents with a consanguineous partner were more positive, estimated the risk for the offspring lower and were less positive about the provision of risk information to consanguineous couples when compared with respondents without a consanguineous partner. Participants of Turkish origin had a more negative attitude towards consanguinity and estimated the reproductive risk higher than Moroccan participants. More than half of the respondents thought that information should be given before marriage, whereas only 10% thought it should never be provided. The general practitioner was most often mentioned (54%) as the designated professional to inform people. Information about genetic risks related to consanguinity should be offered early, preferably before marriage. The diversity of the target population requires various strategies to disseminate information and reach consanguineous couples with the offer of genetic counselling. PMID:23921534

  9. Organ donation consanguinity or universality.

    PubMed

    Kishore, R R

    1996-01-01

    1. Neither the "Diseased Persons" nor the "Genetic Relations" provide an answer to "trading" in human body parts. 2. Live human body constitutes a vital source of supply of organs and tissues and the possibilities of optimum utilisation should be explored. 3. There is no scope for dogmatic postures and open-mindedness should be the approach while dealing with the issue of Organ Transplantation. 4. Society owes a duty to save the file of a dying man and in the event of failure to do so, it is absolutely immoral to interfere with his own arrangements by making unrealistic laws. No immorality is involved if an individual disposes of his spare body parts for a valid consideration to a needy person. 5. The scarcity needs to be urgently overcome otherwise unwarranted trade and crime are liable to thrive. 6. Families are not unconnected or antagonistic fragments of humanity. After thousands of years of continuous efforts the individuals on this earth have attained the stage of organic and functional integration. Atomisation of society on the basis of consanguineous proximities amounts to reversing this holistic trend. Organ transplantation is a functional expression of a highly evolved pursuit with inherent and intimate interaction in the form of organic exchange at the individual level, independent of consanguineous inducements or motivations. As such there is absolutely no scope for restricting organ donations by strangers. 7. Commercialisation should be curbed by making the enforcement agencies more efficient and not by depriving a needy person of his genuine requirements. Legislative craftsmanship lies in providing an answer without curtailing the freedom of the people.

  10. Organ donation consanguinity or universality.

    PubMed

    Kishore, R R

    1996-01-01

    1. Neither the "Diseased Persons" nor the "Genetic Relations" provide an answer to "trading" in human body parts. 2. Live human body constitutes a vital source of supply of organs and tissues and the possibilities of optimum utilisation should be explored. 3. There is no scope for dogmatic postures and open-mindedness should be the approach while dealing with the issue of Organ Transplantation. 4. Society owes a duty to save the file of a dying man and in the event of failure to do so, it is absolutely immoral to interfere with his own arrangements by making unrealistic laws. No immorality is involved if an individual disposes of his spare body parts for a valid consideration to a needy person. 5. The scarcity needs to be urgently overcome otherwise unwarranted trade and crime are liable to thrive. 6. Families are not unconnected or antagonistic fragments of humanity. After thousands of years of continuous efforts the individuals on this earth have attained the stage of organic and functional integration. Atomisation of society on the basis of consanguineous proximities amounts to reversing this holistic trend. Organ transplantation is a functional expression of a highly evolved pursuit with inherent and intimate interaction in the form of organic exchange at the individual level, independent of consanguineous inducements or motivations. As such there is absolutely no scope for restricting organ donations by strangers. 7. Commercialisation should be curbed by making the enforcement agencies more efficient and not by depriving a needy person of his genuine requirements. Legislative craftsmanship lies in providing an answer without curtailing the freedom of the people. PMID:8692005

  11. Elevation deficiency in children with recessive RDH12-related retinopathy.

    PubMed

    AlBakri, Amani; Alkuraya, Fowzan S; Khan, Arif O

    2015-12-01

    Children with retinal dystrophies often have nonspecific strabismus, but vertical incomitant deviations are uncommon. We report 4 children from 3 consanguineous families with bilateral elevation deficiency in the context of retinal dystrophy. All were found to harbor recessive mutations in retinal dehydrogenase 12 (RDH12). PMID:26691045

  12. Isotretinoin treatment of autosomal recessive congenital ichthyosis complicated by coexisting dysferlinopathy.

    PubMed

    Mashiah, J; Harel, A; Bitterman, O; Sagi, L; Gat, A; Fellig, Y; Ben-Shachar, S; Sprecher, E

    2016-06-01

    Consanguinity is known to be associated with an increase in the prevalence of autosomal recessive disorders such as autosomal recessive congenital ichthyosis (ARCI). ARCI often responds well to retinoid treatment. We describe a patient with ARCI who improved under isotretinoin treatment. The patient subsequently developed elevated levels of serum creatinine phosphokinase (CPK), which led to the diagnosis of a second autosomal recessive disorder, dysferlinopathy, a rare myopathy characterized by muscle weakness, decreased tendon reflexes and marked elevation of CPK levels. This report demonstrates the need for physicians to remain alert to the possible coexistence of rare and mutually relevant disorders in populations with a high rate of consanguinity. PMID:26620441

  13. Papillon–Lefevre syndrome: Reporting consanguinity as a risk factor

    PubMed Central

    Shah, Aasim Farooq; Tangade, Pradeep; Agarwal, Swatantra

    2014-01-01

    Papillon–Lefevre syndrome (PLS) is an autosomal recessive genetic disorder characterized by palmoplantar hyperkeratosis associated with severe early-onset periodontitis and premature loss of primary and permanent teeth. This report describes two cases of PLS in 28-year-old female and 16-year-old male siblings with consanguineously married parents. The patients presented to the Department of Public Health Dentistry of a dental education and research institute in India with thickening, flaking, and scaling of the skin on the palms and soles of the feet. On oral examination, the female patient presented completely resorbed maxillary and mandibular alveolar ridges with retention of only the third molars. The male patient retained only teeth 18, 13, 28, 38, and 45. Based on complete histories and clinical examination findings, a final diagnosis of PLS was made and treatment was initiated using an interdisciplinary dental approach in both cases. PMID:25057233

  14. Papillon-Lefevre syndrome: Reporting consanguinity as a risk factor.

    PubMed

    Shah, Aasim Farooq; Tangade, Pradeep; Agarwal, Swatantra

    2014-07-01

    Papillon-Lefevre syndrome (PLS) is an autosomal recessive genetic disorder characterized by palmoplantar hyperkeratosis associated with severe early-onset periodontitis and premature loss of primary and permanent teeth. This report describes two cases of PLS in 28-year-old female and 16-year-old male siblings with consanguineously married parents. The patients presented to the Department of Public Health Dentistry of a dental education and research institute in India with thickening, flaking, and scaling of the skin on the palms and soles of the feet. On oral examination, the female patient presented completely resorbed maxillary and mandibular alveolar ridges with retention of only the third molars. The male patient retained only teeth 18, 13, 28, 38, and 45. Based on complete histories and clinical examination findings, a final diagnosis of PLS was made and treatment was initiated using an interdisciplinary dental approach in both cases.

  15. Consanguineous marriage and reproduction in Beirut, Lebanon.

    PubMed

    Khlat, M

    1988-08-01

    Effects of consanguineous marriages on couples' fertility and on offspring mortality were investigated in Beirut through a population-based health survey of 2,752 households. A multistage random sampling procedure was used, and information was obtained from all ever-married women in the household about their reproductive performance and genealogical relationship with spouse; demographic and socioeconomic information was also recorded. Twenty-five percent of all marriages were between relatives, and the spouses were first cousins in approximately 57% of all consanguineous marriages. Total pregnancies, live births, and living children were significantly higher among consanguineous couples than among nonconsanguineous ones, as was the proportion dead among children ever born. However, no difference remained in either fertility or mortality, when allowance was made for socioeconomic status, religious affiliation, and marriage duration. The issue of confounding is discussed, and the lack of significant pattern in the final analysis is interpreted as resulting from a long-term practice of consanguineous marriages.

  16. A community genetics perspective on consanguineous marriage.

    PubMed

    Bittles, A H

    2008-01-01

    Consanguineous marriage has long been a controversial topic, with particular attention focused on adverse health outcomes. Unfortunately, the studies that have been conducted on consanguinity to date have usually lacked control for important sociodemographic variables, such as maternal age and birth intervals, and in estimating specific disease gene frequency, they have ignored the influence of population sub-division. Inadequate attention has also been paid to the social benefits associated with intra-familial marriage, resulting in a biased overall cost-benefit assessment. Worldwide, some 1,000 million people live in countries where 20 to more than 50% of marriages are consanguineous, and large migrant communities from these regions are now resident in Western Europe, North America and Oceania. The need for comprehensive and more balanced investigations into all aspects of consanguineous marriage is pressing and merits a substantial international collaborative research effort.

  17. The Genetic Basis of Nonsyndromic Hearing Loss in Indian and Pakistani Populations

    PubMed Central

    Yan, Denise; Kannan-Sundhari, Abhiraami; Vishwanath, Subramanian; Qing, Jie; Mittal, Rahul; Kameswaran, Mohan

    2015-01-01

    Deafness encompasses a series of etiologically heterogeneous disorders with mutations in more than 400 independent genes. However, several studies indicate that a large proportion of both syndromic and nonsyndromic forms of deafness in the racially diverse Indian and Pakistani populations are caused by defects in just a few genes. In these countries, there is a strong cultural preference for consanguineous marriage and an associated relatively high prevalence of genetic disorders. The current Indian population is approximately 1.2 billion and it is estimated that 30,000 infants are born with congenital sensorineural hearing loss (HL) each year. The estimated rate of profound bilateral HL is 1.6 per 1000 in Pakistan and 70% of this HL arises in consanguineous families. Knowledge of the genetic cause of deafness within a distinct population is important for accurate genetic counseling and early diagnosis for timely intervention and treatment options. Many sources and technologies are now available for the testing of hearing efficiency. Population-based screening has been proposed as one of the major strategies for translating genetic and genomic advances into population health gains. This review of the genetics of deafness in Indian and Pakistani populations deals with the major causes of deafness in these countries and prospectives for reducing the incidence of inherited deafness. PMID:26186295

  18. Autosomal Recessive Anhidrotic Ectodermal Dysplasia: A Rare Entity

    PubMed Central

    Ghosh, Sangita; Ghosh, Epsita; Dayal, Surabhi

    2014-01-01

    We describe a case of anhidrotic ectodermal dysplasia (AED) with an autosomal recessive mode of inheritance, a very rare entity, in a 2-year-old female child of two asymptomatic, consanguineous parents. Their previous child also had a similar condition. Autosomal recessive AED (AR-AED) can have its full expression both in males and females and it is clinically indistinguishable from the x-linked recessive AED (XL-AED), which is the most common type of ectodermal dysplasia. Unlike the partially symptomatic carriers of XL-AED, the heterozygotes of AR-AED are phenotypically asymptomatic. PMID:25071285

  19. Consanguinity and genetic diseases in North Africa and immigrants to Europe.

    PubMed

    Anwar, Wagida A; Khyatti, Meriem; Hemminki, Kari

    2014-08-01

    Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease. PMID:25107999

  20. Consanguinity and genetic diseases in North Africa and immigrants to Europe.

    PubMed

    Anwar, Wagida A; Khyatti, Meriem; Hemminki, Kari

    2014-08-01

    Endemic diseases are caused by environmental and genetic factors. While in this special issue several chapters deal with environmental factors, including infections, the present focus is on genetic causes of disease clustering due to inbreeding and recessive disease mechanisms. Consanguinity is implying sharing of genetic heritage because of marriage between close relatives originating from a common ancestor. With limited natural selection, recessive genes may become more frequent in an inbred compared with an outbred population. Consanguinity is common in North Africa (NA), and the estimates range from 40 to 49% of all marriages in Tunisia and 29-33% in Morocco. As a consequence, recessive disorders are common in the NA region, and we give some examples. Thalassaemia and sickle cell disease/anaemia constitute the most common inherited recessive disorders globally and they are common in NA, but with immigration they have spread to Europe and to other parts of the world. Another example is familial Mediterranean fever, which is common in the Eastern Mediterranean area. With immigrantion from that area to Sweden, it has become the most common hereditary autoinflammatory disease in that country, and there is no evidence that any native Swede would have been diagnosed with this disease. The examples discussed in this chapter show that the historic movement of populations and current immigration are influencing the concept of 'endemic' disease.

  1. Consanguinity Mapping of Congenital Heart Disease in a South Indian Population

    PubMed Central

    McGregor, Tracy L.; Misri, Amit; Bartlett, Jackie; Orabona, Guilherme; Friedman, Richard D.; Sexton, David; Maheshwari, Sunita; Morgan, Thomas M.

    2010-01-01

    Background Parental consanguinity is a risk factor for congenital heart disease (CHD) worldwide, suggesting that a recessive inheritance model may contribute substantially to CHD. In Bangalore, India, uncle-niece and first cousin marriages are common, presenting the opportunity for an international study involving consanguinity mapping of structural CHD. We sought to explore the recessive model of CHD by conducting a genome-wide linkage analysis utilizing high-density oligonucleotide microarrays and enrolling 83 CHD probands born to unaffected consanguineous parents. Methodology/Principal Findings In this linkage scan involving single nucleotide polymorphism (SNP) markers, the threshold for genome-wide statistical significance was set at the standard log-of-odds (LOD) score threshold of 3.3, corresponding to 1995∶1 odds in favor of linkage. We identified a maximal single-point LOD score of 3.76 (5754∶1 odds) implicating linkage of CHD with the major allele (G) of rs1055061 on chromosome 14 in the HOMEZ gene, a ubiquitously expressed transcription factor containing leucine zipper as well as zinc finger motifs. Re-sequencing of HOMEZ exons did not reveal causative mutations in Indian probands. In addition, genotyping of the linked allele (G) in 325 U.S. CHD cases revealed neither genotypic nor allele frequency differences in varied CHD cases compared to 605 non-CHD controls. Conclusions/Significance Despite the statistical power of the consanguinity mapping approach, no single gene of major effect could be convincingly identified in a clinically heterogeneous sample of Indian CHD cases born to consanguineous parents. However, we are unable to exclude the possibility that noncoding regions of HOMEZ may harbor recessive mutations leading to CHD in the Indian population. Further research involving large multinational cohorts of patients with specific subtypes of CHD is needed to attempt replication of the observed linkage peak on chromosome 14. In addition, we

  2. Consanguinity and disorders of sex development.

    PubMed

    Bashamboo, Anu; McElreavey, Ken

    2014-01-01

    Disorders of sex development (DSD) are defined as 'congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical' [Lee et al., Pediatrics 2006;118:e488-e500]. Studies conducted in Western countries, with low rates of consanguinity, show that truly ambiguous genitalia have an estimated incidence of 1:5,000 births. There are indications that the prevalence of DSD is higher in endogamous communities. The incidence of ambiguous genitalia in Saudi Arabia has been estimated at 1:2,500 live births; whilst in Egypt, it has been estimated at 1:3,000 live births. This may be due in part to an increase in disorders of androgen synthesis associated with 46,XX DSD. There is clearly a need for further studies to address the frequency of DSD in communities with high levels of consanguinity. This will be challenging, as an accurate diagnosis is difficult and expensive even in specialized centres. In developing countries with high levels of consanguinity, these limitations can be compounded by cultural, social and religious factors. Overall there is an indication that consanguinity may lead to an increase in incidences of both 46,XY and 46,XX DSD, and a co-ordinated study of populations with higher incidences of consanguinity/endogamy is needed to resolve this.

  3. Comments on "Consanguineous Marriages in Pakistan".

    PubMed

    Hakim, A

    1994-01-01

    Some critical comments are made on a paper entitled "Consanguineous Marriages in Pakistan." Most studies have considered early age at marriage, rural or extended family setup and low socioeconomic status when investigating the issue. The background demographic variables and behavioral aspects of consanguinity were studied only by a few, therefore a lack of data exists on pertinent social, cultural, and behavioral dynamics. In Pakistan over 60% of marriages are between first or second cousins. The highest rates of such marriages have been reported in rural areas, among individuals with low educational level, and among the poorest. However, cousin unions are also common among landowning families. In addition to socioeconomic reasons, these marriages are socially acceptable because they facilitate prenuptial negotiations and provide more compatibility between the husband and wife as well as the bride and the mother-in-law. The evidence on consanguinity and fertility is conflicting. The effect of inbreeding on fertility has been demonstrated by most studies. The effect of consanguinity on mortality is also wrought with ambiguities because of methodological flaws. Although the present authors used limited bivariate analysis, they could not account for increased fertility and mortality in consanguineous matings by examining socioeconomic differences and background demographic variables. There is a need to indicate clearly to what extent the genetic effect is responsible for the excess fertility and mortality after controlling for maternal, sociodemographic, and behavioral characteristics. The article made a contribution to elucidating the impact of cousin marriages, a well entrenched custom, on fertility, mortality, and the status of women.

  4. Drivers of Cousin Marriage among British Pakistanis

    PubMed Central

    Shaw, Alison

    2014-01-01

    Background/Aim Why has the apparently high rate of cousin marriage among Bradford Pakistanis been sustained, 50 years since Pakistani migration to Britain began? Methods A review of the anthropological literature on Pakistani migration and settlement, British Pakistani marriage patterns and the phenomenon of transnational marriage. Results British Pakistanis are diverse in regional origins and social class characteristics, with many Bradford Pakistanis originating from the Mirpur district and northern Punjab. British Pakistani marriages often involve a partner from Pakistan who joins a spouse in the UK. Transnational marriage of first cousins offers relatives in Pakistan opportunities for a ‘better’ life in the West and are important for British Pakistanis for economic, social, cultural and emotional reasons. These processes are also differentially influenced by region of origin and class characteristics in Pakistan as well as by education, employment and locality in Britain. The pattern observed in Bradford may not be applicable nationally. Conclusion Further research examining marital decisions over several generations in families differing by social class, region of origin in Pakistan and locality in Britain is necessary to contextualise the findings from Bradford. PMID:25060267

  5. Recession Rebound

    ERIC Educational Resources Information Center

    Weinstein, Margery

    2011-01-01

    A return to normal after a crisis is a good thing. Who doesn't want back what once seemed lost? The problem is it usually isn't a simple task figuring out how to patch together a scaled-back training program. When the recession hit in fall 2008, trainers were asked to scale down programming and make do with fewer resources. With a recovery in full…

  6. Consanguinity studies in Wisconsin I: secular trends in consanguineous marriage, 1843-1981.

    PubMed

    Lebel, R R

    1983-08-01

    Over 920,000 Roman Catholic marriages have taken place since the Archdiocese of Milwaukee was established in 1843. Most of these records are extant, and all have been examined to ascertain consanguineous marriages. The changing average population coefficient of consanguinity has been calculated, by year and by decade, showing a clear downward trend since the turn of the century. The data are compared with reports of consanguineous marriage incidence from around the world, and in particular with all available previous reports from the United States.

  7. Impact of new genomic tools on the practice of clinical genetics in consanguineous populations: the Saudi experience.

    PubMed

    Alkuraya, F S

    2013-09-01

    Consanguinity is practiced by around one tenth of the world population but its global distribution is far from uniform. In countries where consanguinity is common, a corresponding increase in the frequency of autosomal recessive diseases is usually observed owing to increased risk of homozygosity for ancestral haplotypes (autozygosity or identity by descent) that harbor pathogenic alleles. The burden of these diseases becomes more apparent as the healthcare system makes gains in its fight against communicable diseases in these countries. Recent advances in molecular genetics make it possible to leverage the mechanism by which consanguinity predisposes to the occurrence of autosomal recessive diseases in order to uncover the causal mutations at an efficient and cost-effective way compared to outbred populations. The identification of these mutations at an unprecedented scale has the potential to significantly reshape the practice of clinical genetics in these populations and to offer opportunities for innovative public health policies. This review discusses the impact that new genomic tools have had on a sample patient population and how they can inform future public health policies in ways that might be relevant to other consanguineous populations.

  8. Genomic runs of homozygosity record population history and consanguinity.

    PubMed

    Kirin, Mirna; McQuillan, Ruth; Franklin, Christopher S; Campbell, Harry; McKeigue, Paul M; Wilson, James F

    2010-01-01

    The human genome is characterised by many runs of homozygous genotypes, where identical haplotypes were inherited from each parent. The length of each run is determined partly by the number of generations since the common ancestor: offspring of cousin marriages have long runs of homozygosity (ROH), while the numerous shorter tracts relate to shared ancestry tens and hundreds of generations ago. Human populations have experienced a wide range of demographic histories and hold diverse cultural attitudes to consanguinity. In a global population dataset, genome-wide analysis of long and shorter ROH allows categorisation of the mainly indigenous populations sampled here into four major groups in which the majority of the population are inferred to have: (a) recent parental relatedness (south and west Asians); (b) shared parental ancestry arising hundreds to thousands of years ago through long term isolation and restricted effective population size (N(e)), but little recent inbreeding (Oceanians); (c) both ancient and recent parental relatedness (Native Americans); and (d) only the background level of shared ancestry relating to continental N(e) (predominantly urban Europeans and East Asians; lowest of all in sub-Saharan African agriculturalists), and the occasional cryptically inbred individual. Moreover, individuals can be positioned along axes representing this demographic historic space. Long runs of homozygosity are therefore a globally widespread and under-appreciated characteristic of our genomes, which record past consanguinity and population isolation and provide a distinctive record of the demographic history of an individual's ancestors. Individual ROH measures will also allow quantification of the disease risk arising from polygenic recessive effects.

  9. Attitude of Saudi Arabian adults towards consanguineous marriage

    PubMed Central

    Alharbi, Omar A.; Al-Shaia, Walaa A.; Al-Hamam, Abdulaziz A.; Al-Marzoug, Hala M.; Ahmed, Anwar E.; Bagha, Muhammed

    2015-01-01

    Background: Research on the attitudes of Saudi adults towards consanguinity is scarce. The study aimed to explore the attitudes towards consanguinity and its associations with socio-demographic characteristics in a sample of Saudi adults. Methods: A cross-sectional study was conducted using a self-administered questionnaire. A total of 386 outpatient waiting-area attendees at King Abdul-Aziz Medical City-Riyadh were included. Participants were asked about their socio-demographic characteristics, attitude towards consanguinity and the reasons behind this. Results: The positive attitude towards consanguinity among the study respondents was 48.1% with 95% confidence interval (42.91–53.33%). Social and traditional culture (59.9%) were found to be the predominant reasons for favoring consanguinity in Saudi Arabia. Evidence against a positive attitude towards consanguinity was noted in respondents who received medical information about consanguinity versus those who had not received medical information (42.3% vs. 57%, p-value = 0.008). According to the multivariate logistic model, the odds of a positive attitude towards consanguinity were 2 times higher for males (adjusted odds ratio [aOR]: 2.2; 95% CI: 1.147, 4.290) and 4.1 times higher in respondents in consanguineous marriages (aOR: 4.1; 95% CI: 2.350, 7.156). The odds of a positive attitude towards consanguinity were 50% less in respondents who received health information on consanguinity compared to those who had not received health information about consanguinity (aOR: 0.50; 95% CI: 0.253, 0.863). Conclusion: One in every two Saudi adults favors consanguinity however, Saudi men and women differ in their attitudes towards consanguinity. Receiving health information on consanguinity was associated with a negative attitude towards this practice. PMID:26835408

  10. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia

    PubMed Central

    Nickerson, Sarah L.; Marquis-Nicholson, Renate; Claxton, Karen; Ashton, Fern; Leong, Ivone U. S.; Prosser, Debra O.; Love, Jennifer M.; George, Alice M.; Taylor, Graham; Wilson, Callum; McKinlay Gardner, R. J.; Love, Donald R.

    2015-01-01

    Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias.

  11. [Consanguineous marriage in Turkey and its effects on infant mortality].

    PubMed

    Ulusoy, M; Tuncbilek, E

    1987-01-01

    The authors examine the effects of consanguineous marriage on infant mortality in Turkey. An attempt is made to distinguish the influence of consanguineous marriage from that of selected regional and socioeconomic factors. It is found that "the differences of the average infant mortality rates between consanguineous and non-consanguineous marriages are parallel to the development differences between the regions as well as the conditions of the house which are thought to signify the socioeconomic differences. Although the differences in averages are insignificant statistically, this trend [indicates] that consanguineous marriages [affect] infant mortality." Data are from the 1983 Turkish Fertility, Contraceptive Prevalence and Family Health Status Survey. (SUMMARY IN ENG)

  12. Leishmaniasis in refugee and local Pakistani populations.

    PubMed

    Brooker, Simon; Mohammed, Nasir; Adil, Khaksar; Agha, Said; Reithinger, Richard; Rowland, Mark; Ali, Iftikhar; Kolaczinski, Jan

    2004-09-01

    The epidemiology of anthroponotic cutaneous leishmaniasis was investigated in northwest Pakistan. Results suggested similar patterns of endemicity in both Afghan refugee and Pakistani populations and highlighted risk factors and household clustering of disease. PMID:15498178

  13. A probably distinct autosomal recessive thoraco-limb dysplasia.

    PubMed Central

    Rivera, H; Perez-Salas, J M; Nazara, Z; Ramirez, M L

    1988-01-01

    A Mexican mestizo family is reported in which two opposite sexed sibs, born to consanguineous parents, had a skeletal dysplasia. The salient features were a bell shaped thorax owing to short ribs, short limbed dwarfism, pelvic hypoplasia, dislocatable radial heads, elongated distal fibulae, and improvement with age. It is concluded that the present observation probably represents a distinct autosomal recessive thoraco-limb dysplasia identifiable at birth. Images PMID:3184141

  14. A study of possible deleterious effects of consanguinity.

    PubMed

    Abdulrazzaq, Y M; Bener, A; al-Gazali, L I; al-Khayat, A I; Micallef, R; Gaber, T

    1997-03-01

    The aim of the study was to determine whether consanguineous marriages result in reproductive wastage and an increased incidence of illness in the offspring in a community with a long history of inbreeding and an expected high rate of consanguineous marriage. A representative sample of 2200 women aged > or = 15 years from Dubai and Al Ain, two cities in the United Arab Emirates, representing on the one hand a modern metropolis and on the other a traditional society, were studied. A questionnaire, which included questions on age, parity, gravidity, number of stillbirths, number of abortions, number of children alive, neonatal deaths and specific illnesses in children, was administered by nurses in antenatal and gynaecological clinics in the two cities. The rate of consanguineous marriage was 50.5% and parity, gravidity, ages and number of children were similar in consanguineous and non-consanguineous groups. There was no significant difference in rates of abortion, stillbirth and neonatal death between the two groups. Overall, there was statistically significant higher reproductive wastage in consanguineous couples, but when the category of less than second cousins was excluded from the consanguineous group no difference was found in reproductive wastage between consanguineous and non-consanguineous marriages. Children born to consanguineous unions also had significantly higher incidences of illnesses (37.1%) than those of non-consanguineous unions (29%). The occurrence of malignancies, congenital abnormalities, mental retardation and physical handicap was significantly higher in offspring of consanguineous than non-consanguineous marriages. In conclusion, consanguinity did not result in reproductive wastage, but was found to be an important factor in the causation of specific illnesses in offspring.

  15. Consanguinity and endogamy in Northern Tunisia and its impact on non-syndromic deafness.

    PubMed

    Ben Arab, Saida; Masmoudi, Saber; Beltaief, Najeh; Hachicha, Slah; Ayadi, Hammadi

    2004-07-01

    Deafness is an important health problem in the Tunisian population, especially in isolates where the prevalence ranges from 2 to 8%. To evaluate the effect of inbred unions on deafness, a study was conducted on 5,020 individuals (160 are deaf) between 2000 and 2002 in the North of Tunisia. The coefficient of inbreeding for all individuals and the levels of inbreeding in ten districts were computed. The higher levels were obtained in the rural districts. Our study revealed that geographic isolation, social traditions, and parental involvement in mode selection all contribute to increase consanguinity in these regions. The mean inbreeding seems to be similar to those estimated in highly inbred isolates in the world. The relative risk of the 35delG mutation, the single most frequent allele for non-syndromic recessive deafness in Tunisia, was estimated from the observed inbreeding coefficient and found to be 10.76 (SD 7.74) for first-cousin marriages, which are the most common form of consanguineous marriage encountered. Our knowledge of the risk rate of deafness and our understanding of consanguinity is required for the prevention of genetic deafness in the Tunisian population.

  16. Consanguineous marriage among rural Arabs in Israel.

    PubMed

    Freundlich, E; Hino, N

    1984-11-01

    The prevalence of consanguineous marriages was examined among the Arab rural population in the Western Galilee region in Israel. The survey was conducted by questioning women attending Mother and Child Health Centers, or those met on the main street of the village. The overall figures were unusually high (39%), including those for first and second cousins. They were highest in the Druze population (49%), lower in the Moslems (40%) and still lower in the Christians (29%) (P less than 0.001). The most common type was first-cousin marriages, especially where the husband's father and the wife's father were brothers. The prevalence of consanguineous marriages was higher in the younger generation whose members had remained in their family village. These findings indicate that the traditional way of life, with its close family relationships, is still most common in the Arab rural society in Israel. The high prevalence of consanguinity is an unfavorable factor in this population's health condition. It is believed that the present educational and occupational changes will gradually alter this custom.

  17. A study of consanguineous marriage as a risk factor for developing comitant strabismus.

    PubMed

    Bagheri, Mansooreh; Farvardin, Majid; Saadat, Mostafa

    2015-04-01

    Inheritance has an important role in the etiology of comitant strabismus. Consanguineous marriage is a leading factor in birth defects in which inheritance has a role. The aim of this study is to reveal if consanguineous marriage increases the risk of developing comitant strabismus. We included 461 patients who underwent primary surgery for comitant strabismus in Shiraz University Khalili Hospital (Fars province, southern Iran) between years 2003 and 2013 in our study. All the patients were living in Shiraz, Iran. Patients were categorized into the following 4 groups: (1) intermittent or constant exotropia, (2) infantile esotropia, (3) non-accommodative acquired esotropia, and (4) accommodative acquired esotropia. A total of 421 healthy children who were born in Shiraz, at the same period of time, were also studied as a control group. Presence and type of the consanguineous marriages were evaluated in the parents of the patients and control group by a questionnaire. Mean of inbreeding coefficient (α) was calculated in each group of patients and was compared with those of control group. The proportion of parental first cousin marriage was 37.7 and 23.5 % among patient and control groups. The mean of inbreeding coefficients (α) were 0.0236, 0.0283, 0.0288, and 0.0236 in four groups of the patients, respectively. The mean of inbreeding coefficient was 0.0263 in total patients, which was significantly higher than 0.0164 of control group (T = 5.27, df = 880, P < 0.001). Patients with non-accommodative acquired esotropia had the highest mean of inbreeding coefficient (α) (0.0288). It seems that recessive form of inheritance plays an important role in the etiology of comitant strabismus. Modified screening programs may be needed for earlier detection of strabismus in the offspring of consanguineous couples.

  18. An autosomal recessive syndrome of cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE).

    PubMed Central

    Giannotti, A; Digilio, M C; Mingarelli, R; Dallapiccola, B

    1995-01-01

    We report a brother and sister affected by a constellation of malformations, including cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE). A similar association has been reported previously by Richieri-Costa and Orquizas in a male patient born to consanguineous parents. An autosomal recessive pattern of inheritance is proposed for this syndrome. Images PMID:7897634

  19. Consanguineous marriage in a newly developed country: the Qatari population.

    PubMed

    Bener, Abdulbari; Alali, Khalid A

    2006-03-01

    This study examines the frequency of consanguineous marriage and coefficient of inbreeding in the State of Qatar. The study was conducted in semi-urban areas of Doha between January and May 2004. A sample of 1515 married Qatari females aged 15 years and over participated. The degree of consanguinity between each female and her spouse, and degree of consanguinity between their parents were recorded. The rate of consanguinity in the present generation was high (54.0%) with a coefficient of inbreeding of 0.02706. The commonest type of consanguineous marriage was between first cousins (34.8%). Double first cousin marriages were common (3.1%) compared with other populations. The consanguinity rate in the State of Qatar has increased from 41.8% to 54.5% in one generation.

  20. Consanguineous marriages : Preconception consultation in primary health care settings.

    PubMed

    Hamamy, Hanan

    2012-07-01

    Consanguinity is a deeply rooted social trend among one-fifth of the world population mostly residing in the Middle East, West Asia and North Africa, as well as among emigrants from these communities now residing in North America, Europe and Australia. The mounting public awareness on prevention of congenital and genetic disorders in offspring is driving an increasing number of couples contemplating marriage and reproduction in highly consanguineous communities to seek counseling on consanguinity. Primary health care providers are faced with consanguineous couples demanding answers to their questions on the anticipated health risks to their offspring. Preconception and premarital counseling on consanguinity should be part of the training of health care providers particularly in highly consanguineous populations.

  1. Is consanguineous marriage religiously encouraged? Islamic and Iranian considerations.

    PubMed

    Akrami, Seyed Mohammad; Osati, Zahra

    2007-03-01

    Consanguineous marriage has had considerable attention as a causative factor in the prevalence of genetic disorders. Iran, with its majority Muslim population, has a high rate of consanguineous marriage. In Iranian tradition, first cousin marriage is an acceptable and appreciated custom. However, there seems to be no encouragement of consanguineous marriage in the Islamic context; it is merely mentioned as a traditional and common custom. This paper may help medical professionals providing premarital genetic counselling, who are regularly asked about consanguineous marriage, especially in Islamic communities. Increased public awareness via the mass media would seem to be a priority.

  2. Identification of a homozygous splice site mutation in the dynein axonemal light chain 4 gene on 22q13.1 in a large consanguineous family from Pakistan with congenital mirror movement disorder.

    PubMed

    Ahmed, Iltaf; Mittal, Kirti; Sheikh, Taimoor I; Vasli, Nasim; Rafiq, Muhammad Arshad; Mikhailov, Anna; Ohadi, Mehrnaz; Mahmood, Huda; Rouleau, Guy A; Bhatti, Attya; Ayub, Muhammad; Srour, Myriam; John, Peter; Vincent, John B

    2014-11-01

    Mirror movements (MRMV) are involuntary movements on one side of the body that mirror voluntary movements on the opposite side. Congenital mirror movement disorder is a rare, typically autosomal-dominant disorder, although it has been suspected that some sporadic cases may be due to recessive inheritance. Using a linkage analysis and a candidate gene approach, two genes have been implicated in congenital MRMV disorder to date: DCC on 18q21.2 (MRMV1), which encodes a netrin receptor, and RAD51 on 15q15.1 (MRMV2), which is involved in the maintenance of genomic integrity. Here, we describe a large consanguineous Pakistani family with 11 cases of congenital MRMV disorder reported across five generations, with autosomal recessive inheritance likely. Sanger sequencing of DCC and RAD51 did not identify a mutation. We then employed microarray genotyping and autozygosity mapping to identify a shared region of homozygosity-by-descent among the affected individuals. We identified a large autozygous region of ~3.3 Mb on chromosome 22q13.1 (Chr22:36605976-39904648). We used Sanger sequencing to exclude several candidate genes within this region, including DMC1 and NPTXR. Whole exome sequencing was employed, and identified a splice site mutation in the dynein axonemal light chain 4 gene, DNAL4. This splice site change leads to skipping of exon 3, and omission of 28 amino acids from DNAL4 protein. Linkage analysis using Simwalk2 gives a maximum Lod score of 6.197 at this locus. Whether or how DNAL4 function may relate to the function of DCC or RAD51 is not known. Also, there is no suggestion of primary ciliary dyskinesis, situs inversus, or defective sperm in affected family members, which might be anticipated given a putative role for DNAL4 in axonemal-based dynein complexes. We suggest that DNAL4 plays a role in the cytoplasmic dynein complex for netrin-1-directed retrograde transport, and in commissural neurons of the corpus callosum in particular. This, in turn, could lead

  3. Absence of cystic fibrosis mutations in a large Asian population sample and occurrence of a homozygous S549N mutation in an inbred Pakistani family.

    PubMed Central

    Curtis, A; Richardson, R J; Boohene, J; Jackson, A; Nelson, R; Bhattacharya, S S

    1993-01-01

    The occurrence of cystic fibrosis is very rare in the Asian population. Carriers of the mutations most commonly found in Caucasians were not detected in a large Asian population sample of almost 900 chromosomes. However, an affected Pakistani child born to consanguineous parents was further investigated and shown to be homozygous for the mutation S549N (G-->A). Molecular and clinical data are presented which may improve our understanding of the phenotypic effects of the S549N mutation in the CFTR gene. Images PMID:7680378

  4. Unexpected genetic heterogeneity in a large consanguineous Brazilian pedigree presenting deafness.

    PubMed

    Lezirovitz, Karina; Pardono, Eliete; de Mello Auricchio, Maria T B; de Carvalho E Silva, Fernando L; Lopes, Juliana J; Abreu-Silva, Ronaldo S; Romanos, Jihane; Batissoco, Ana C; Mingroni-Netto, Regina C

    2008-01-01

    Nonsyndromic autosomal recessive deafness accounts for 80% of hereditary deafness. To date, 52 loci responsible for autosomal recessive deafness have been mapped and 24 genes identified. Here, we report a large inbred Brazilian pedigree with 26 subjects affected by prelingual deafness. Given the extensive consanguinity found in this pedigree, the most probable pattern of inheritance is autosomal recessive. However, our linkage and mutational analysis revealed, instead of an expected homozygous mutation in a single gene, two different mutant alleles and a possible third undetected mutant allele in the MYO15A gene (DFNB3 locus), as well as evidence for other causes for deafness in the same pedigree. Among the 26 affected subjects, 15 were homozygous for the novel c.10573delA mutation in the MYO15A gene, 5 were compound heterozygous for the mutation c.10573delA and the novel deletion c.9957_9960delTGAC and one inherited only a single c.10573delA mutant allele, while the other one could not be identified. Given the extensive consanguinity of the pedigree, there might be at least one more deafness locus segregating to explain the condition in some of the subjects whose deafness is not clearly associated with MYO15A mutations, although overlooked environmental causes could not be ruled out. Our findings illustrate a high level of etiological heterogeneity for deafness in the family and highlight some of the pitfalls of genetic analysis of large genes in extended pedigrees, when homozygosity for a single mutant allele is expected.

  5. Consanguinity trends and correlates in the Palestinian Territories.

    PubMed

    Assaf, Shireen; Khawaja, Marwan

    2009-01-01

    Secondary analysis of the trends and correlates of consanguinity in the Palestinian Territories was conducted using data from two separate surveys in 1995 and 2004. The analysis was conducted on ever-married women aged 15-54 who were asked about their relation to their husband in both surveys. A total of 16,197 women in 1995 and 4971 women in 2004 were successfully interviewed. Consanguinity was found to be widely practised in the Palestinian Territories with rates of total consanguinity reaching 45% of all marriages in 2004. Analysis was conducted with the data from the two surveys combined and this indicated that consanguinity was significantly decreasing with time after controlling for other variables. Age of the women, their age at marriage, region and locality type they lived in and their standard of living were all found to be significant predictors of consanguinity. The education level of the women was not found to be significant. After controlling for the survey year, women's labour force status was also found to be a non-significant predictor of consanguinity. Although consanguinity was found to be significantly decreasing slowly with time after controlling for other variables, the future trends of consanguinity are not known due to the unstable political situation in the territories, which could have a direct effect on marriage patterns. PMID:18549512

  6. Prevalence of consanguineous marriages and associated factors among Israeli Bedouins.

    PubMed

    Na'amnih, Wasef; Romano-Zelekha, Orly; Kabaha, Ahmed; Rubin, Liza Pollack; Bilenko, Natalya; Jaber, Lutfi; Honovich, Mira; Shohat, Tamy

    2014-10-01

    The Bedouin population in Israel is a semi-nomadic traditional patriarchal society. Consanguineous marriages are very common, contributing to high rates of congenital malformations and genetic diseases, resulting in high infant mortality. Data on consanguineous marriages among Bedouins in Israel are limited. This study examined the current prevalence of consanguineous marriages and their determinants among Israeli Bedouins. One thousand two hundred ninety Bedouin women who delivered in the maternity wards of the only hospital serving the Bedouin population were interviewed between November 2009 and January 2010. The prevalence of consanguineous marriages was 44.8 %. The most common type of spousal relationship was first cousins (65.7 % of all consanguineous marriages). The mean inbreeding coefficient was 0.0238. Factors significantly associated with consanguinity were less years of schooling (OR 0.94, 95 % CI (0.88-0.99), p = 0.02) and younger age at marriage of the wife (OR 0.90, 95 % CI (0.80-0.96), p = 0.0002). In conclusion, the rate of consanguineous marriages among Bedouins is very high, making this population at risk for congenital malformations and genetic diseases. Efforts should be directed at better education and provision of premarital and prenatal counseling on the health consequences of consanguineous marriages and the possibilities to lower those risks.

  7. Finding genetic contributions to sporadic disease: a recessive locus at 12q24 commonly contributes to patent ductus arteriosus.

    PubMed

    Mani, Arya; Meraji, Seyed-Mahmoud; Houshyar, Roozbeh; Radhakrishnan, Jayaram; Mani, Alaleh; Ahangar, Mehrabeh; Rezaie, Tayebeh M; Taghavinejad, Mohammad-Ali; Broumand, Behrooz; Zhao, Hongyu; Nelson-Williams, Carol; Lifton, Richard P

    2002-11-12

    The causes of many sporadic diseases are unexplained; the contribution of recessive loci with reduced penetrance is one possibility that has been difficult to explore. We describe an approach to this problem by first searching for diseases with higher prevalence in populations with high rates of consanguinity, then determining whether disease cases are more commonly the product of consanguinous union than controls in such populations, followed by analysis of genetic linkage in consanguinous cases. We demonstrate the utility of this approach by investigation of congenital heart disease in Iran. We found that patent ductus arteriosus (PDA), a common congenital heart disease, accounts for a higher fraction of congenital heart disease in Iran (15%) than in the United States (2-7%). Moreover, Iranian PDA cases demonstrated a marked increase of parental consanguinity (63%), compared with the general Iranian population (25%) or control cases with tetralogy of Fallot (30%). The recurrence of PDA among siblings was 5%. A genomewide analysis of linkage in 21 unrelated consanguinous PDA cases demonstrated a multipoint logarithm of odds score of 6.27 in favor of linkage of PDA to a 3-centimorgan interval of chromosome 12q24, with 53% of kindreds linked. These findings together establish a recessive component to PDA and implicate a single locus, PDA1, in one third or more of all PDA cases in Iran; they further suggest a role for this locus in PDA worldwide. Finally, these results suggest a general approach to the identification of recessive contributions to sporadic diseases.

  8. Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

    PubMed Central

    Liu, Yo-Tsen; Hersheson, Joshua; Plagnol, Vincent; Fawcett, Katherine; Duberley, Kate E C; Preza, Elisavet; Hargreaves, Iain P; Chalasani, Annapurna; Laurá, Matilde; Wood, Nick W; Reilly, Mary M; Houlden, Henry

    2014-01-01

    Background The autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC). Methods We report two siblings from a consanguineous Pakistani family who presented with cerebellar ataxia and severe myoclonus from adolescence. Whole exome sequencing and biochemical assessment of fibroblasts were performed in the index patient. Results A novel homozygous frameshift mutation in ADCK3 (p.Ser616Leufs*114), was identified in both siblings. This frameshift mutation results in the loss of the stop codon, extending the coding protein by 81 amino acids. Significant CoQ10 deficiency and reduced MRC enzyme activities in the index patient's fibroblasts suggested that the mutant protein may reduce the efficiency of mitochondrial electron transfer. CoQ10 supplementation was initiated following these genetic and biochemical analyses. She gained substantial improvement in myoclonic movements, ataxic gait and dysarthric speech after treatment. Conclusion This study highlights the importance of diagnosing ADCK3 mutations and the potential benefit of treatment for patients. The identification of this new mutation broadens the phenotypic spectrum associated with ADCK3 mutations and provides further understanding of their pathogenic mechanism. PMID:24218524

  9. Journalism Education in the Pakistani Borderlands

    ERIC Educational Resources Information Center

    Pintak, Lawrence

    2012-01-01

    Students brave roadside bombs and Taliban threats while on class assignments. Professors are kidnapped and killed. Campus radio stations get regular visits from military intelligence. Welcome to journalism education in Pakistan's tribal areas. The region is off-limits to most outsiders, so students find themselves reporting for Pakistani and…

  10. The Religification of Pakistani-American Youth

    ERIC Educational Resources Information Center

    Ghaffar-Kucher, Ameena

    2012-01-01

    This article describes a cultural production process called religification, in which religious affiliation, rather than race or ethnicity, has become the core category of identity for working-class Pakistani-American youth in the United States. In this dialectical process, triggered by political changes following the September 11 terrorist…

  11. Contribution of GLC3A locus to Primary Congenital Glaucoma in Pakistani population

    PubMed Central

    Bashir, Rasheeda; Sanai, Mahrukh; Azeem, Adnan; Altaf, Imran; Saleem, Faiza; Naz, Sadaf

    2014-01-01

    Objectives: To check the contribution of GLC3A locus to primary congenital glaucoma in the Pakistani population. Methods: We enrolled twenty-nine sporadic cases and three families with multiple individuals affected with recessive primary congenital glaucoma in the year 2013. It was a genetic linkage study accomplished jointly in Department of Biotechnology of Lahore College for Women University and School of Biological Sciences, University of the Punjab, Lahore. Samples from all affected individuals were checked for homozygosity for alleles of microsatellite markers spanning CYP1B1 at GLC3A locus. Genotyping was performed with fluorescently labeled primers by capillary electrophoresis. For familial cases, linkage was evaluated by checking the co-segregation of the phenotype with the genotypes. Two-point LOD score was calculated for each microsatellite marker with MLINK. Results: Our study revealed that GLCA3 may contribute to glaucoma in 17% of the sporadic cases and patients in 2 of the 3 families. Conclusions: This data suggests that the GLC3A may make an important contribution to autosomal recessive primary congenital glaucoma in the Pakistani population. Genotyping and Sequencing of more families will be helpful to identify the common mutations in CYP1B1 in future. PMID:25674135

  12. Thomsen or Becker myotonia? A novel autosomal recessive nonsense mutation in the CLCN1 gene associated with a mild phenotype.

    PubMed

    Gurgel-Giannetti, Juliana; Senkevics, Adriano S; Zilbersztajn-Gotlieb, Dinorah; Yamamoto, Lydia U; Muniz, Viviane P; Pavanello, Rita C M; Oliveira, Acary B; Zatz, Mayana; Vainzof, Mariz

    2012-02-01

    We describe a large Brazilian consanguineous kindred with 3 clinically affected patients with a Thomsen myotonia phenotype. They carry a novel homozygous nonsense mutation in the CLCN1 gene (K248X). None of the 6 heterozygote carriers show any sign of myotonia on clinical evaluation or electromyography. These findings confirm the autosomal recessive inheritance of the novel mutation in this family, as well as the occurrence of phenotypic variability in the autosomal recessive forms of myotonia.

  13. Recurrent mutation in CDMP1 in a family with Grebe chondrodysplasia: broadening the phenotypic manifestation of syndrome in Pakistani population.

    PubMed

    Mumtaz, Sara; Riaz, Hafiza Fizzah; Touseef, Mohammad; Basit, Sulman; Faiyaz Ul Haque, Muhammad; Malik, Sajid

    2015-01-01

    Grebe syndrome (OMIM-200700) is a very rare type of acromesomelic dysplasia with autosomal recessive inheritance. We studied a Pakistani family with two affected individuals having typical features of Grebe chondrodysplasia. Patients were observed with short and deformed limbs having a proximo-distal gradient of severity. Hind-limbs were more severely affected than fore-limbs. Digits on autopods were very short and nonfunctional. Index subject also had nearsightedness. However, symptoms in the craniofacial and axial skeleton were minimal. Genetic analysis revealed four base pair insertion mutation (c.1114insGAGT) in gene coding cartilage-derived morphogenetic protein-1 (CDMP1). This mutation was predicted to cause premature stop codon. The clinical presentation in this study broadens the range of phenotypes associated with CDMP1 mutation in Pakistani population. PMID:26870132

  14. Recurrent mutation in CDMP1 in a family with Grebe chondrodysplasia: broadening the phenotypic manifestation of syndrome in Pakistani population

    PubMed Central

    Mumtaz, Sara; Riaz, Hafiza Fizzah; Touseef, Mohammad; Basit, Sulman; Haque, Muhammad Faiyaz Ul; Malik, Sajid

    2015-01-01

    Grebe syndrome (OMIM-200700) is a very rare type of acromesomelic dysplasia with autosomal recessive inheritance. We studied a Pakistani family with two affected individuals having typical features of Grebe chondrodysplasia. Patients were observed with short and deformed limbs having a proximo-distal gradient of severity. Hind-limbs were more severely affected than fore-limbs. Digits on autopods were very short and nonfunctional. Index subject also had nearsightedness. However, symptoms in the craniofacial and axial skeleton were minimal. Genetic analysis revealed four base pair insertion mutation (c.1114insGAGT) in gene coding cartilage-derived morphogenetic protein-1 (CDMP1). This mutation was predicted to cause premature stop codon. The clinical presentation in this study broadens the range of phenotypes associated with CDMP1 mutation in Pakistani population. PMID:26870132

  15. A novel mutation in FGD4/FRABIN causes Charcot Marie Tooth disease type 4H in patients from a consanguineous Tunisian family.

    PubMed

    Boubaker, Chokri; Hsairi-Guidara, Inès; Castro, Christel; Ayadi, Ines; Boyer, Amandine; Kerkeni, Emna; Courageot, Joël; Abid, Imen; Bernard, Rafaëlle; Bonello-Palot, Nathalie; Kamoun, Fatma; Cheikh, Hassen Ben; Lévy, Nicolas; Triki, Chahnez; Delague, Valérie

    2013-07-01

    Charcot-Marie-Tooth (CMT) disease constitutes a clinically and genetically heterogeneous group of hereditary neuropathies characterized by progressive muscular and sensory loss in the distal extremities with chronic distal weakness, deformation of the feet, and loss of deep tendon reflexes. CMT4H is an autosomal recessive demyelinating subtype of CMT, due to mutations in FGD4/FRABIN, for which nine mutations are described to date. In this study, we describe three patients from a consanguineous Tunisian family, presenting with severe, early onset, slowly progressive, autosomal recessive demyelinating CMT, complicated by mild to severe kyphoscoliosis, consistent with CMT4H. In these patients, we report the identification of a novel homozygous frameshift mutation in FGD4: c.514_515insG; p.Ala172Glyfs*27. Our study reports the first mutation identified in FGD4 in Tunisian patients affected with CMT. It further confirms the important clinical heterogeneity observed in patients with mutations in FGD4 and the lack of phenotype/genotype correlations in CMT4H. Our results suggest that FGD4 should be screened in other early-onset CMT subtypes, regardless of the severity of the phenotype, and particularly in patients of consanguineous descent. In Tunisians, as in other populations with high consanguinity rates, screening of genes responsible for rare autosomal recessive CMT subtypes should be prioritized.

  16. Loss of function mutations in RP1 are responsible for retinitis pigmentosa in consanguineous familial cases

    PubMed Central

    Kabir, Firoz; Ullah, Inayat; Ali, Shahbaz; Gottsch, Alexander D.H.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose This study was undertaken to identify causal mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous families. Methods Large consanguineous families were ascertained from the Punjab province of Pakistan. An ophthalmic examination consisting of a fundus evaluation and electroretinography (ERG) was completed, and small aliquots of blood were collected from all participating individuals. Genomic DNA was extracted from white blood cells, and a genome-wide linkage or a locus-specific exclusion analysis was completed with polymorphic short tandem repeats (STRs). Two-point logarithm of odds (LOD) scores were calculated, and all coding exons and exon–intron boundaries of RP1 were sequenced to identify the causal mutation. Results The ophthalmic examination showed that affected individuals in all families manifest cardinal symptoms of RP. Genome-wide scans localized the disease phenotype to chromosome 8q, a region harboring RP1, a gene previously implicated in the pathogenesis of RP. Sanger sequencing identified a homozygous single base deletion in exon 4: c.3697delT (p.S1233Pfs22*), a single base substitution in intron 3: c.787+1G>A (p.I263Nfs8*), a 2 bp duplication in exon 2: c.551_552dupTA (p.Q185Yfs4*) and an 11,117 bp deletion that removes all three coding exons of RP1. These variations segregated with the disease phenotype within the respective families and were not present in ethnically matched control samples. Conclusions These results strongly suggest that these mutations in RP1 are responsible for the retinal phenotype in affected individuals of all four consanguineous families. PMID:27307693

  17. Consanguinity and rare mutations outside of MCCC genes underlie nonspecific phenotypes of MCCD

    PubMed Central

    Shepard, Peter J.; Barshop, Bruce A.; Baumgartner, Matthias R.; Hansen, John-Bjarne; Jepsen, Kristen; Smith, Erin N.; Frazer, Kelly A.

    2015-01-01

    Purpose 3-Methylcrotonyl-CoA carboxylase deficiency (MCCD) is an autosomal recessive disorder of leucine catabolism that has a highly variable clinical phenotype, ranging from acute metabolic acidosis to nonspecific symptoms such as developmental delay, failure to thrive, hemiparesis, muscular hypotonia, and multiple sclerosis. Implementation of newborn screening for MCCD has resulted in broadening the range of phenotypic expression to include asymptomatic adults. The purpose of this study was to identify factors underlying the varying phenotypes of MCCD. Methods We performed exome sequencing on DNA from 33 cases and 108 healthy controls. We examined these data for associations between either MCC mutational status, genetic ancestry, or consanguinity and the absence or presence/specificity of clinical symptoms in MCCD cases. Results We determined that individuals with nonspecific clinical phenotypes are highly inbred compared with cases that are asymptomatic and healthy controls. For 5 of these 10 individuals, we discovered a homozygous damaging mutation in a disease gene that is likely to underlie their nonspecific clinical phenotypes previously attributed to MCCD. Conclusion Our study shows that nonspecific phenotypes attributed to MCCD are associated with consanguinity and are likely not due to mutations in the MCC enzyme but result from rare homozygous mutations in other disease genes. PMID:25356967

  18. Frameshift mutation in the APOA5 gene causing hypertriglyceridemia in a Pakistani family: Management and considerations for cardiovascular risk.

    PubMed

    Thériault, Sébastien; Don-Wauchope, Andrew; Chong, Michael; Lali, Ricky; Morrison, Katherine M; Paré, Guillaume

    2016-01-01

    We report a novel homozygous apolipoprotein A5 (APOA5) frameshift mutation (c.G425del-C, p.Arg143AlafsTer57) identified in a 12-year-old boy of Pakistani origin with severe hypertriglyceridemia (up to 35 mmol/L) and type V hyperlipoproteinemia. The patient did not respond to fibrate therapy, but his condition improved under a very low fat diet, although compliance was suboptimal. Heterozygous status was detected in both parents (consanguineous union) and one sibling, all showing moderate hypertriglyceridemia (between 5 and 10 mmol/L). There was a significant family history of premature cardiovascular disease. The index case was also diagnosed with a coronary artery anomaly. Considering the recently reported association of rare mutations in APOA5 with the risk of early myocardial infarction, we discuss the implications of these findings for the young man and his family. PMID:27678447

  19. Meckel Gruber Syndrome: Second trimester diagnosis of a case in a non-consanguineous marriage.

    PubMed

    Alam, Areej; Adhi, Mehreen; Bano, Raffat; Zubair, Aisha; Mushtaq, Ammara

    2013-01-01

    Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder, incompatible with life. It is characterized by enlarged polycystic kidneys and post axial polydactyly. Foetal or neonatal death is caused by pulmonary hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed for her current pregnancy at 18 weeks of gestation showed features consistent with MKS. The termination of pregnancy was declined and a live newborn female was delivered via an emergency caeserean section at 34 weeks of gestation due to previous history of lower segment caesarean section (LSCS) & leaking. Physical examination of the neonate confirmed the features of MKS. The neonate died within 4-5 hours of birth. This case represented a second trimester diagnosis of a recurrent case of MKS in a non-consanguineous marriage.

  20. WDR62 missense mutation in a consanguineous family with primary microcephaly.

    PubMed

    Bacino, Carlos A; Arriola, Luis A; Wiszniewska, Joanna; Bonnen, Penelope E

    2012-03-01

    We report on a consanguineous couple with two affected sons who presented with primary microcephaly and moderate to severe intellectual disabilities. A SNP array uncovered two overlapping regions of copy-neutral absence of heterozygosity (AOH) in both sibs. This led to sequencing of WDR62, a gene that codes for a spindle pole protein recently identified as a cause of primary microcephaly. A homozygous missense mutation in WDR62, p.E400K, was found in both boys and segregated with the condition in this family. WDR62 is one of seven genes responsible for autosomal recessive primary microcephaly (MCPH), and appears to be one of the most frequently involved in MCPH following ASPM. Studies of ASPM and WDR62 should perhaps be pursued in all cases of primary microcephaly with or without gross brain malformations.

  1. Prevalence of consanguineous marriages in South Sinai, Egypt.

    PubMed

    Yamamah, G; Abdel-Raouf, E; Talaat, A; Saad-Hussein, A; Hamamy, H; Meguid, N A

    2013-01-01

    A total of 3961 married couples from six major geographical areas representing the South Sinai governorates in Egypt were studied to assess the rate of consanguineous marriage. The population of six selected areas (St Catherines, Nuweiba, Abu Rudeis, Ras Sudr, El Tor and Abu Zenima) were subdivided into Bedouin, urban and mixed populations. A questionnaire-based interview was conducted showing that the consanguinity rate in this region is 37.5%, with the highest rate recorded in Abu Rudeis (52.3%) and lowest rate in Nuweiba (24.1%). Consanguinity was significantly higher among the Bedouin population compared with the urban population in Abu Rudeis, Ras Sudr, El Tor and Abu Zenima, while in St Catherines and Nuweiba there was no statistically significant difference. Among consanguineous couples, 5%, 60% and 35% were double first cousins, first cousins and second cousins respectively. The mean inbreeding coefficient α of the studied population was 0.01845.

  2. Consanguinity and increased risk for schizophrenia in Egypt

    PubMed Central

    Mansour, Hader; Fathi, Warda; Klei, Lambertus; Wood, Joel; Chowdari, Kodavali; Watson, Annie; Eissa, Ahmed; Elassy, Mai; Ali, Ibtihal; Salah, Hala; Yassin, Amal; Tobar, Salwa; El-Boraie, Hala; Gaafar, Hanan; Ibrahim, Nahed E.; Kandil, Kareem; El-Bahaei, Wafaa; El-Boraie, Osama; Alatrouny, Mohamed; El-Chennawi, Farha; Devlin, Bernie; Nimgaonkar, Vishwajit L.

    2010-01-01

    Background Consanguinity has been suggested as a risk factor for psychsoses in some Middle Eastern countries, but adequate control data are unavailable. Our recent studies in Egypt have shown elevated parental consanguinity rates among patients with bipolar I disorder (BP1), compared with controls. We have now extended our analyses to Schizophrenia (SZ) in the same population. Methods A case-control study was conducted at Mansoura University Hospital, Mansoura, Egypt (SZ, n = 75; controls, n = 126, and their available parents). The prevalence of consanguinity was estimated from family history data (‘self report’), followed by DNA analysis using short tandem repeat polymorphisms (STRPs, n = 63) (‘DNA-based’ rates). Results Self reported consanguinity was significantly elevated among the patients (SZ: 46.6%, controls: 19.8%, OR 3.53, 95% CI 1.88, 6.64; p = 0.000058, 1 d.f.). These differences were confirmed using DNA based estimates for coefficients of inbreeding (inbreeding coefficients as means ± standard error, cases: 0.058 ± 0.007, controls: 0.022 ± 0.003). Conclusions Consanguinity rates are signifcantly elevated among Egyptian SZ patients in the Nile delta region. The associations are similar to those observed with BP1 in our earlier study. If replicated, the substantial risk associated with consanguinity raises public health concerns. They may also pave the way for gene mapping studies. PMID:20435442

  3. [Factors influencing the frequency of consanguineous marriages in Japan].

    PubMed

    Imaizumi, Y

    1987-04-01

    A survey of consanguineous marriages in Japan was conducted through questionnaires in 1983. The total number of couples studied was 9225, chosen from 6 widely different areas of Japan. The rates of first cousin marriages and of total consanguineous marriages for all areas were 1.6% and 3.9%, respectively. The rate of total consanguineous marriages was 10 times higher in Fukue-Shi (7.9%) than Asahikawa city area (.78%). The rate of total consanguineous marriages decreased with the marriage year in Japan, where the rate of first cousin marriages has changed remarkably. The rates of consanguineous marriages were estimated according to marital distance between birth places, socioeconomic classes, religion, marriage form, opportunity of encounter, and motivation towards marriage. Among educational groups, the rate was highest in graduates of junior high school for husbands and wives, and the rate was lowest in college or university graduates. Occupationally, the rate was the highest in agriculture, forestry, and fishery for husbands and wives, and the rate was lowest among salesmen for husbands and in professional occupations and researchers for wives. As for opportunities of encounter, the rate was 22-29 times higher in the group for friendship from the time of childhood (25.8%) than in those for school, workplace, and social gatherings (1.2%) and for chance meetings (.9%). A recommendation by parents and relatives was the most frequent reason for consanguineous marriage for both husbands and wives, followed by knowledge of the partner by relatives.

  4. SNP Analysis and Whole Exome Sequencing: Their Application in the Analysis of a Consanguineous Pedigree Segregating Ataxia

    PubMed Central

    Nickerson, Sarah L.; Marquis-Nicholson, Renate; Claxton, Karen; Ashton, Fern; Leong, Ivone U. S.; Prosser, Debra O.; Love, Jennifer M.; George, Alice M.; Taylor, Graham; Wilson, Callum; McKinlay Gardner, R. J.; Love, Donald R.

    2015-01-01

    Autosomal recessive cerebellar ataxia encompasses a large and heterogeneous group of neurodegenerative disorders. We employed single nucleotide polymorphism (SNP) analysis and whole exome sequencing to investigate a consanguineous Maori pedigree segregating ataxia. We identified a novel mutation in exon 10 of the SACS gene: c.7962T>G p.(Tyr2654*), establishing the diagnosis of autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS). Our findings expand both the genetic and phenotypic spectrum of this rare disorder, and highlight the value of high-density SNP analysis and whole exome sequencing as powerful and cost-effective tools in the diagnosis of genetically heterogeneous disorders such as the hereditary ataxias. PMID:27600236

  5. Genetic counseling of consanguineous families. Use of Smith's method to calculate recurrence risks in multifactorial inheritance in consanguineous matings.

    PubMed Central

    Bonaiti, C

    1978-01-01

    A modification of Smith's method is described for deriving recurrence risks for multifactorial conditions when parents are related. Using cleft palate as an example, the possible increased risks caused by consanguinity are discussed. PMID:641942

  6. Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinsm (OCA)

    SciTech Connect

    Tripathi, R.K.; Droetto, S.; Strunk, K.M.; Holmes, S.A.; Spritz, R.A. ); Bundey, S.; Musarella, M.A.

    1993-12-01

    Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by deficient synthesis of melanin pigment. Type I (tyrosinase-deficient) OCA results from mutations of the tyrosinase gene (TYR gene) encoding tyrosinase, the enzyme that catalyzes the first two steps of melanin biosynthesis. Mutations of the TYR gene have been identified in a large number of patients, most of Caucasian ethnic origin, with various forms of type I OCA. The authors present an analysis of the TYR gene in eight Indo-Pakistani patients with type I OCA. The authors describe four novel TYR gene mutations and a fifth mutation previously observed in a Caucasian patient. 16 refs., 6 figs.

  7. An Investigation of Generic Structures of Pakistani Doctoral Thesis Acknowledgements

    ERIC Educational Resources Information Center

    Rofess, Sakander; Mahmood, Muhammad Asim

    2015-01-01

    This paper investigates Pakistani doctoral thesis acknowledgements from genre analysis perspective. A corpus of 235 PhD thesis acknowledgements written in English was taken from Pakistani doctoral theses collected from eight different disciplines. HEC Research Repository of Pakistan was used as a data sources. The theses written by Pakistani…

  8. Consanguineous marriages in Beirut: time trends, spatial distribution.

    PubMed

    Khlat, M

    1988-01-01

    To provide some information on consanguineous marriages, a population based-description of consanguineous marriages in Beirut is presented. A health survey of the city of Beirut, undertaken from July 1, 1983, to August 31, 1984, covered 13,736 individuals, comprising 3033 ever- married women. These women provided information on their marriage and the kinship between the spouses, as well as on the religion, educational and occupational status of their husbands. Armitage's test was used to assess the significance of the time gradient in consanguineous marriages and Bartholomew's test used to assess the significance of the variation in religion, educational level, and occupational status of the residents by level of endogamy in the sector. The overall prevalence of consanguineous marriages was 25%. 56% of marriages occurred between 1st cousins. Splitting the 1st cousin marriages by pedigree showed that patrilateral parallel-cousin marriage was well represented, amounting to 52.2% of all cousin marriages. Over time, consanguineous marriages significantly declined the mean proportion varying from 30% before 1950 to 25% between 1950-69, to about 20% starting form 1970. Cousin marriages remained stable over time, while marriages between distant relatives underwent a significant decline. Rates of consanguineous marriages was computed by sector and mapped. Rates were higher in the western part of the city, comprising a majority of Muslim inhabitants, than in the eastern part, mostly Christian. The higher the proportion of consanguineous marriages, the higher the proportion of husbands of low educational level, of low occupational status, and of Muslim religion.

  9. Starving for Recess

    ERIC Educational Resources Information Center

    Patt, Mary Johnson

    2011-01-01

    Every weekday, millions of American schoolchildren throw away their half-eaten cafeteria lunches so that they can run outside to play. The traditional placement of lunch before recess, coupled with the recent decline in overall recess time to meet academic time constraints, forces children to choose between two essential needs: (1) food; and (2)…

  10. Recess--It's Indispensable!

    ERIC Educational Resources Information Center

    Jarrett, Olga; Waite-Stupiansky, Sandra

    2009-01-01

    The demise of recess in many elementary schools--and of outdoor play in general--is an issue of great concern to many members of the Play, Policy, and Practice Interest Forum. Most people remember recess as an important part of the school day. It was a time to be outdoors; to organize games; to play on the swings, slides, and other playground…

  11. More Recess Time, Please!

    ERIC Educational Resources Information Center

    Chang, Rong; Coward, Fanni Liu

    2015-01-01

    Students in Shanghai, China, get much more recess time than their U.S. counterparts throughout their education. As U.S. education reform efforts seek ways of raising achievement, they have begun replacing recess with academic time. The lesson from Shanghai is that this may not be the best strategy. But whether the Shanghai system of more and…

  12. Recession in the Regions

    ERIC Educational Resources Information Center

    Plant, Helen

    2009-01-01

    National policy stresses the key role of adult learning and skills in securing economic recovery. This close linking of adult learning policy to the recession agenda raises important questions. How has the recession impacted on the implementation of adult learning policy? What has it meant for service delivery? And what have been the consequences…

  13. Pattern of central nervous system anomalies in a population with a high rate of consanguineous marriages.

    PubMed

    Al-Gazali, L I; Sztriha, L; Dawodu, A; Bakir, M; Varghese, M; Varady, E; Scorer, J; Abdulrazzaq, Y M; Bener, A; Padmanabhan, R

    1999-02-01

    Nine thousand six hundred and ten births were prospectively studied in the three major hospitals in Al-Ain, United Arab Emirates (UAE) between October 1995 and January 1997. Babies suspected of, or diagnosed, as having central nervous system (CNS) abnormalities were evaluated by a neonatologist, a clinical geneticist and a pediatric neurologist. Brain computerized tomography/magnetic resonance imaging (CT/MRI) was performed on all babies suspected of having CNS abnormalities. In addition, metabolic screening and chromosome analysis were also performed when indicated. Of the 225 babies with congenital anomalies identified, 31 had CNS abnormalities (3.2/1000). Syndromic abnormalities of the CNS were present in 13 cases (42%), chromosomal abnormalities in one case (3.2%) and the rest included: neural tube defect (NTD) in 11 cases (36%), holoprosencephaly in two cases (6.4%) and hydrocephalus in four cases (12.9%). Detailed analysis of the syndromic types revealed that out of the 13 cases, 12 were inherited as autosomal recessive (AR) and in one case the inheritance was undetermined. Consanguinity with high level of inbreeding was present in 12 cases and the majority of the syndromes identified were extremely rare. The study indicates that CNS anomalies are fairly common in the UAE, particularly, the recessive syndromic types. Careful and detailed analysis of such anomalies is required so that accurate genetic advice can be given. PMID:10189086

  14. Consanguinity on Robinson Crusoe Island, an isolated Chilean population.

    PubMed

    Villanueva, Pia; Fernández, Maria A; De Barbieri, Zulema; Palomino, Hernán

    2014-07-01

    The population of Robinson Crusoe Island is estimated at 633 inhabitants. The current population has a common origin from the first eight families who colonized the island at the end of the 19th century. The objective of this study was to determine the rates of consanguinity, the average coefficients of inbreeding, the types of consanguineous marriages and the inbreeding evolution between 1900 and 2000 on the island. All marriages registered on the island, from the last colonization until 2000 (417 in total), were included in the analysis. In addition, extended genealogies were obtained. The consanguinity rate was 14.9% and the average coefficient of inbreeding (α) 54.05 × 10(-4). The most frequent type of consanguineous marriages was between second cousins, followed by first cousins. The average value of the first/second cousin ratio was 1.11. The population of Robinson Crusoe Island has a high rate of inbreeding. The unique characteristic of the island - its small current population, originating from just a few families, with small rate of gene flow - could explain the observed high and increasing consanguinity.

  15. The impact of consanguinity on neonatal and infant health.

    PubMed

    Bittles, A H; Black, M L

    2010-11-01

    Marriage between biological relatives is widely popular in many parts of the world, with over 1000 million people living in countries where 20-50+% of unions are contracted between couples related as second cousins or closer. Consanguinity is, however, a controversial topic, in part due to public misunderstanding, complicated by often exaggerated past estimates of the adverse health outcomes. While some consanguineous couples are at high risk of conceiving a child with a genetic disorder, they are a small minority. Thus a multi-population meta-analysis has indicated an excess infant death rate of 1.1% in the progeny of first cousins, and even this figure may be compromised by inadequate control for non-genetic variables. The benefits as well as the disadvantages of consanguineous marriage are assessed and discussed, with specific consideration given to the health of migrant communities in Western countries, among whom first cousin marriage remains preferential.

  16. Consanguineous marriage within social/occupational class boundaries in Pakistan.

    PubMed

    Shami, S A; Grant, J C; Bittles, A H

    1994-01-01

    Data on patterns of consanguineous marriage were collected from 5340 families resident in eight cities in the Pakistan province of Punjab. To assess whether social and/or occupational class was interacting with consanguinity, information also was obtained on the hereditary qaum to which each family belonged. In the present generation 46.5% of all marriages were contracted at the level of second cousin or closer, with an average coefficient of inbreeding (F) of 0.0286, and the results indicated that in each of the seventeen qaums there was strong preference for marriage to a close biological relative. However, significant differences existed in the distribution of consanguineous marriage by qaum membership, which could interfere with the interpretation of studies into the biological effects of inbreeding. PMID:8200883

  17. Consanguineous marriage within social/occupational class boundaries in Pakistan.

    PubMed

    Shami, S A; Grant, J C; Bittles, A H

    1994-01-01

    Data on patterns of consanguineous marriage were collected from 5340 families resident in eight cities in the Pakistan province of Punjab. To assess whether social and/or occupational class was interacting with consanguinity, information also was obtained on the hereditary qaum to which each family belonged. In the present generation 46.5% of all marriages were contracted at the level of second cousin or closer, with an average coefficient of inbreeding (F) of 0.0286, and the results indicated that in each of the seventeen qaums there was strong preference for marriage to a close biological relative. However, significant differences existed in the distribution of consanguineous marriage by qaum membership, which could interfere with the interpretation of studies into the biological effects of inbreeding.

  18. Mutation of ATF6 causes autosomal recessive achromatopsia.

    PubMed

    Ansar, Muhammad; Santos-Cortez, Regie Lyn P; Saqib, Muhammad Arif Nadeem; Zulfiqar, Fareeha; Lee, Kwanghyuk; Ashraf, Naeem Mahmood; Ullah, Ehsan; Wang, Xin; Sajid, Sundus; Khan, Falak Sher; Amin-ud-Din, Muhammad; Smith, Joshua D; Shendure, Jay; Bamshad, Michael J; Nickerson, Deborah A; Hameed, Abdul; Riazuddin, Saima; Ahmed, Zubair M; Ahmad, Wasim; Leal, Suzanne M

    2015-09-01

    Achromatopsia (ACHM) is an early-onset retinal dystrophy characterized by photophobia, nystagmus, color blindness and severely reduced visual acuity. Currently mutations in five genes CNGA3, CNGB3, GNAT2, PDE6C and PDE6H have been implicated in ACHM. We performed homozygosity mapping and linkage analysis in a consanguineous Pakistani ACHM family and mapped the locus to a 15.12-Mb region on chromosome 1q23.1-q24.3 with a maximum LOD score of 3.6. A DNA sample from an affected family member underwent exome sequencing. Within the ATF6 gene, a single-base insertion variant c.355_356dupG (p.Glu119Glyfs*8) was identified, which completely segregates with the ACHM phenotype within the family. The frameshift variant was absent in public variant databases, in 130 exomes from unrelated Pakistani individuals, and in 235 ethnically matched controls. The variant is predicted to result in a truncated protein that lacks the DNA binding and transmembrane domains and therefore affects the function of ATF6 as a transcription factor that initiates the unfolded protein response during endoplasmic reticulum (ER) stress. Immunolabeling with anti-ATF6 antibodies showed localization throughout the mouse neuronal retina, including retinal pigment epithelium, photoreceptor cells, inner nuclear layer, inner and outer plexiform layers, with a more prominent signal in retinal ganglion cells. In contrast to cytoplasmic expression of wild-type protein, in heterologous cells ATF6 protein with the p.Glu119Glyfs*8 variant is mainly confined to the nucleus. Our results imply that response to ER stress as mediated by the ATF6 pathway is essential for color vision in humans. PMID:26063662

  19. Barriers to contraceptive use among Pakistani couples.

    PubMed

    Harel, K

    1997-01-01

    Despite the existence of a family planning program in Pakistan since 1965 and widespread knowledge among Pakistanis about contraception, there is a high level of unmet need for family planning. One recent survey found that while 53% of married women express the desire to avoid pregnancy, less than 20% use contraception. A recent Population Council study conducted in urban and rural areas of Punjab province investigated personal beliefs, family circumstances, social norms, and gender relations among 1310 married women and 554 of their husbands. The unmet need for contraception was highest among women over age 30 years, those with more living children, less educated women, and women living in rural areas. The study found that while most Pakistanis approve of family planning, obstacles to contraceptive use exist in most marriages. 97% of respondents who wanted another child wished for a boy. That preference for sons influences contraceptive use behavior. The fear of social disapproval of contraceptive use, perceived opposition from in-laws and husbands, and fear of health side effects and divine punishment were major reasons identified against contraceptive use. Female contraceptive users were more autonomous and likely to make domestic decisions without consulting their husbands, while husbands defer to social and cultural norms. PMID:12292988

  20. Sociodemographic correlates of consanguineous marriage in the Muslim population of India.

    PubMed

    Hussain, R; Bittles, A H

    2000-10-01

    Using data derived from the 1992-1993 National Family Health Survey, the sociodemographic characteristics of consanguineous marriage were determined in the Muslim population of India. In this nationally representative sample of 8436 women, consanguineous marriages accounted for 22.0% of the total. No differences between the consanguineous and non-consanguineous groups were observed in terms of mean age at marriage or mean age at cohabitation. The study confirmed the negative association between consanguineous marriage and maternal education but also indicated that women in consanguineous unions were more likely to be employed, albeit mainly in agricultural work on behalf of the family. Consanguineous couples more frequently lived in smaller towns and in an extended family environment. Somewhat conflicting results were obtained with indicators of socioeconomic status, but the overall picture suggested that consanguineous households had greater access to consumer goods because of their larger number of co-resident persons.

  1. Increased Probability of Co-Occurrence of Two Rare Diseases in Consanguineous Families and Resolution of a Complex Phenotype by Next Generation Sequencing

    PubMed Central

    Lal, Dennis; Neubauer, Bernd A.; Toliat, Mohammad R.; Altmüller, Janine; Thiele, Holger; Nürnberg, Peter; Kamrath, Clemens; Schänzer, Anne; Sander, Thomas; Hahn, Andreas; Nothnagel, Michael

    2016-01-01

    Massively parallel sequencing of whole genomes and exomes has facilitated a direct assessment of causative genetic variation, now enabling the identification of genetic factors involved in rare diseases (RD) with Mendelian inheritance patterns on an almost routine basis. Here, we describe the illustrative case of a single consanguineous family where this strategy suffered from the difficulty to distinguish between two etiologically distinct disorders, namely the co-occurrence of hereditary hypophosphatemic rickets (HRR) and congenital myopathies (CM), by their phenotypic manifestation alone. We used parametric linkage analysis, homozygosity mapping and whole exome-sequencing to identify mutations underlying HRR and CM. We also present an approximate approach for assessing the probability of co-occurrence of two unlinked recessive RD in a single family as a function of the degree of consanguinity and the frequency of the disease-causing alleles. Linkage analysis and homozygosity mapping yielded elusive results when assuming a single RD, but whole-exome sequencing helped to identify two mutations in two genes, namely SLC34A3 and SEPN1, that segregated independently in this family and that have previously been linked to two etiologically different diseases. We assess the increase in chance co-occurrence of rare diseases due to consanguinity, i.e. under circumstances that generally favor linkage mapping of recessive disease, and show that this probability can increase by several orders of magnitudes. We conclude that such potential co-occurrence represents an underestimated risk when analyzing rare or undefined diseases in consanguineous families and should be given more consideration in the clinical and genetic evaluation. PMID:26789268

  2. Classic Case Report of Donohue Syndrome (Leprechaunism; OMIM *246200): The Impact of Consanguineous Mating.

    PubMed

    Nijim, Yousif; Awni, Youssef; Adawi, Amin; Bowirrat, Abdalla

    2016-02-01

    Donohue syndrome ([DS]; leprechaunism) describes a genetic autosomal recessive disorder that results from the presence of homozygous or compound heterozygous mutations in the insulin receptor gene (INSR; 19p13.3-p13.2).Donohue syndrome is associated with a fatal congenital form of dwarfism with features of intrauterine and postnatal growth retardation, exaggerated hyperglycemia with hyperinsulinism and dysmorphic abnormalities.We present a case of DS owing to the rarity of this syndrome (1 case in every million births). We discuss how the disease presents, its genetic underpinning, and its prevention.The case was encountered in an Arab male born on 1 September, 2014, for consanguineous parents. The delivery was via cesarean section at 37 weeks gestation due to severe intrauterine growth restriction and nonprogress labor term. The patient was admitted to the Neonatal Intensive Care Unit due to infection, and jaundice. Dysmorphic features, abnormalities of the craniofacial region, low birth weight, skin abnormalities, abdominal distension and hypertrichosis were observed. Laboratory examinations showed, hyperinsulinism, increased C-peptide, thrombocytopenia, leucopenia, and anemia.The diagnosis of DS was done based on the combinations of typical dysmorphic characteristics, clinical evaluation, supported by genetic analysis and exaggerated biochemical results. Genetic diagnosis of DS was performed through analysis of DNA via polymerase chain reaction (PCR). A qualitative real-time PCR was used, to monitor the amplification of a targeted DNA molecule during the PCR. Other technique using sequencing of the INSR gene, which permits genetic diagnosis, counseling, and antenatal diagnoses in subsequent pregnancies, were also performed.Treatment of DS is supportive and requires the combined efforts of a multidisciplinary team, which include pediatricians, endocrinologists, dermatologists, and other health care professionals. Currently, treatment with recombinant insulin

  3. Consanguinity and Birth Defects in the Jerusalem Perinatal Study Cohort

    PubMed Central

    Harlap, S.; Kleinhaus, K.; Perrin, M.C.; Calderon-Margalit, R.; Paltiel, O.; Deutsch, L.; Manor, O.; Tiram, E.; Yanetz, R.; Friedlander, Y.

    2008-01-01

    Background While parental consanguinity is known to increase the risk of birth defects in offspring, it is hard to quantify this risk in populations where consanguinity is prevalent. Methods To support ongoing studies of cancer and of psychiatric disease, we studied relationships of consanguinity to 1,053 major birth defects in 29,815 offspring, born in 1964–1976. To adjust for confounding variables (geographic origin, social class and hospital), we constructed logistic regression models, using GEE to take into account correlations between sibs. Odds ratios (ORs) and 95% confidence limits were estimated in comparison to a reference group of offspring with grandfathers born in different countries. Results With 10.1% of offspring having consanguineous parents, the adjusted OR for major birth defect was 1.41 (1.12–1.74). Offspring of marriages between uncles-nieces, first cousins and more distant relatives showed adjusted ORs of 2.36 (0.98–5.68), 1.59 (1.22–2.07) and 1.20 (0.89–1.59) respectively. For descendents of grandfathers born in the same country, but not known to be related, the OR was 1.05 (0.91–1.21); these showed increased risk associated with ancestries in Western Asia (1.27, 1.04–1.55, p < 0.02) or Europe (1.13, 0.79–1.80). Conclusions A strong association of consanguinity with poverty and low education points to the need to avoid exposure to environmental hazards in these families. PMID:18493143

  4. Acceptability of GM foods among Pakistani consumers.

    PubMed

    Ali, Akhter; Rahut, Dil Bahadur; Imtiaz, Muhammad

    2016-04-01

    In Pakistan majority of the consumers do not have information about genetically modified (GM) foods. In developing countries particularly in Pakistan few studies have focused on consumers' acceptability about GM foods. Using comprehensive primary dataset collected from 320 consumers in 2013 from Pakistan, this study analyzes the determinants of consumers' acceptability of GM foods. The data was analyzed by employing the bivariate probit model and censored least absolute deviation (CLAD) models. The empirical results indicated that urban consumers are more aware of GM foods compared to rural consumers. The acceptance of GM foods was more among females' consumers as compared to male consumers. In addition, the older consumers were more willing to accept GM food compared to young consumers. The acceptability of GM foods was also higher among wealthier households. Low price is the key factor leading to the acceptability of GM foods. The acceptability of the GM foods also reduces the risks among Pakistani consumers.

  5. Acceptability of GM foods among Pakistani consumers.

    PubMed

    Ali, Akhter; Rahut, Dil Bahadur; Imtiaz, Muhammad

    2016-04-01

    In Pakistan majority of the consumers do not have information about genetically modified (GM) foods. In developing countries particularly in Pakistan few studies have focused on consumers' acceptability about GM foods. Using comprehensive primary dataset collected from 320 consumers in 2013 from Pakistan, this study analyzes the determinants of consumers' acceptability of GM foods. The data was analyzed by employing the bivariate probit model and censored least absolute deviation (CLAD) models. The empirical results indicated that urban consumers are more aware of GM foods compared to rural consumers. The acceptance of GM foods was more among females' consumers as compared to male consumers. In addition, the older consumers were more willing to accept GM food compared to young consumers. The acceptability of GM foods was also higher among wealthier households. Low price is the key factor leading to the acceptability of GM foods. The acceptability of the GM foods also reduces the risks among Pakistani consumers. PMID:27494790

  6. Wolcott-Rallison Syndrome Is the Most Common Genetic Cause of Permanent Neonatal Diabetes in Consanguineous Families

    PubMed Central

    Rubio-Cabezas, Oscar; Patch, Ann-Marie; Minton, Jayne A. L.; Flanagan, Sarah E.; Edghill, Emma L.; Hussain, Khalid; Balafrej, Amina; Deeb, Asma; Buchanan, Charles R.; Jefferson, Ian G.; Mutair, Angham; Hattersley, Andrew T.; Ellard, Sian

    2009-01-01

    Context and Objective: Mutations in EIF2AK3 cause Wolcott-Rallison syndrome (WRS), a rare recessive disorder characterized by early-onset diabetes, skeletal abnormalities, and liver dysfunction. Although early diagnosis is important for clinical management, genetic testing is generally performed after the full clinical picture develops. We aimed to identify patients with WRS before any other abnormalities apart from diabetes are present and study the overall frequency of WRS among patients with permanent neonatal diabetes. Research Design and Methods: The coding regions of EIF2AK3 were sequenced in 34 probands with infancy-onset diabetes with a clinical phenotype suggestive of WRS (n = 28) or homozygosity at the WRS locus (n = 6). Results: Twenty-five probands (73.5%) were homozygous or compound heterozygous for mutations in EIF2AK3. Twenty of the 26 mutations identified were novel. Whereas a diagnosis of WRS was suspected before genetic testing in 22 probands, three patients with apparently isolated diabetes were diagnosed after identifying a large homozygous region encompassing EIF2AK3. In contrast to nonconsanguineous pedigrees, mutations in EIF2AK3 are the most common known genetic cause of diabetes among patients born to consanguineous parents (24 vs. < 2%). Age at diabetes onset and birth weight might be used to prioritize genetic testing in the latter group. Conclusions: WRS is the most common cause of permanent neonatal diabetes mellitus in consanguineous pedigrees. In addition to testing patients with a definite clinical diagnosis, EIF2AK3 should be tested in patients with isolated neonatal diabetes diagnosed after 3 wk of age from known consanguineous families, isolated populations, or countries in which inbreeding is frequent. PMID:19837917

  7. Clinical and molecular characterisation of Bardet-Biedl syndrome in consanguineous populations: the power of homozygosity mapping.

    PubMed

    Abu Safieh, L; Aldahmesh, M A; Shamseldin, H; Hashem, M; Shaheen, R; Alkuraya, H; Al Hazzaa, S A F; Al-Rajhi, A; Alkuraya, F S

    2010-04-01

    Bardet-Biedl syndrome (BBS) is a ciliopathy with pleiotropic effect that manifests primarily as renal insufficiency, polydactyly, retinal dystrophy and obesity. The current phenotype-genotype correlation is insufficient to predict the likely causative mutation that makes sequencing of all 14 BBS genes an often necessary but highly complicated way to identify the underlying genetic defect in affected patients. In this study, homozygosity mapping is shown as a robust approach that is highly suited for genetically heterogeneous autosomal recessive disorders in populations in which consanguinity is prevalent. This approach allowed us to quickly identify seven novel mutations in seven families with BBS. Some of these mutations would have been missed by unguided routine sequencing, which suggests that missed mutations in known BBS genes could be more common than previously thought. This study, the largest to date on Saudi BBS families, also revealed interesting phenotypic aspects of BBS, including the first report of non-syndromic retinitis pigmentosa as a novel BBS phenotype.

  8. Bloom syndrome: an analysis of consanguineous families assigns the locus mutated to chromosome band 15q26.1.

    PubMed Central

    German, J; Roe, A M; Leppert, M F; Ellis, N A

    1994-01-01

    By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous, far more often than expected (P < 0.0001 by chi 2). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a "reverse" genetics definition of the primary defect in Bloom syndrome. Images PMID:8022833

  9. Exome sequencing in a consanguineous family clinically diagnosed with early-onset Alzheimer's disease identifies a homozygous CTSF mutation.

    PubMed

    Bras, Jose; Djaldetti, Ruth; Alves, Ana Margarida; Mead, Simon; Darwent, Lee; Lleo, Alberto; Molinuevo, Jose Luis; Blesa, Rafael; Singleton, Andrew; Hardy, John; Clarimon, Jordi; Guerreiro, Rita

    2016-10-01

    We have previously reported the whole genome genotyping analysis of 2 consanguineous siblings clinically diagnosed with early onset Alzheimer's disease (AD). In this analysis, we identified several large regions of homozygosity shared between both affected siblings, which we suggested could be candidate loci for a recessive genetic lesion underlying the early onset AD in these cases. We have now performed exome sequencing in one of these siblings and identified the potential cause of disease: the CTSF c.1243G>A:p.Gly415Arg mutation in homozygosity. Biallelic mutations in this gene have been shown to cause Type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis with some cases resembling the impairment seen in AD. PMID:27524508

  10. Bloom syndrome: An analysis of consanguineous families assigns the locus mutated to chromosome band 15q26. 1

    SciTech Connect

    German, J.; Roe, A.M.; Ellis, N.A. ); Leppert, M.F. )

    1994-07-05

    By the principle of identity by descent, parental consanguinity in individuals with rare recessively transmitted disorders dictates homozygosity not just at the mutated disease-associated locus but also at sequences that flank that locus closely. In 25 of 26 individuals with Bloom syndrome examined whose parents were related, a polymorphic tetranucleotide repeat in an intron of the protooncogene FES was homozygous far more often than expected (P < 0.0001 by x[sup 2]). Therefore, BLM, the gene that when mutated gives rise to Bloom syndrome, is tightly linked to FES, a gene whose chromosome position is known to be 15q26.1. This successful approach to the assignment of the Bloom syndrome locus to one short segment of the human genome simultaneously (i) demonstrates the power of homozygosity mapping and (ii) becomes the first step in a [open quotes]reverse[close quotes] genetics definition of the primary defect in Bloom syndrome.

  11. The Recess Renaissance

    ERIC Educational Resources Information Center

    Keeler, Rusty

    2015-01-01

    The author tells of his work around the country and world on transforming how schools do recess, free play, and outside time by transforming their outdoor spaces to match. Instead of a playground of fixed structures like traditional school grounds, newer spaces are filled with loose materials that children can use to build forts, dens, and tree…

  12. 'I don't see any point in telling them': attitudes to sharing genetic information in the family and carrier testing of relatives among British Pakistani adults referred to a genetics clinic.

    PubMed

    Shaw, Alison; Hurst, Jane A

    2009-04-01

    The sharing of genetic information following the diagnosis of a genetic condition can be important for managing familial risks for genetic conditions. This paper explores factors that impede or facilitate the sharing of genetic information within a sample of British Pakistani families. It draws from research investigating understandings of genetics and inheritance, attitudes to prenatal diagnosis and risk communication in the family that used methods of participant observation and interview with adults from 66 families of Pakistani origin referred to a genetics clinic in southern England. We found a lack of English often restricted one partner's access to genetic information and partners fluent in English sometimes withheld information to protect a partner (usually the wife) from blame, stigma or feelings of marital insecurity. Many couples felt genetic information was private to them as a couple and were unwilling to share it with the wider family, commenting on its potentially stigmatizing and emotionally and socially disruptive effects on themselves, their child and their marriage, as well as on the marriage prospects of other family members. Those who sought carrier testing because of a family history did so when considering their own marriage or parenting, sometimes on the insistence of an affected relative, but did not readily discuss carrier testing with other relatives. Despite the complex consanguinity in some families, a family-based approach to risk management is not necessarily any easier among British Pakistanis than other ethnic groups. PMID:19052940

  13. Homozygosity mapping: a way to map human recessive traits with the DNA of inbred children

    SciTech Connect

    Lander, E.S.; Botstein, D.

    1987-06-19

    An efficient strategy for mapping human genes that cause recessive traits has been devised that uses mapped restriction fragment length polymorphisms (RFLPs) and the DNA of affected children from consanguineous marriages. The method involves detection of the disease locus by virtue of the fact that the adjacent region will preferentially be homozygous by descent in such inbred children. A single affected child of a first-cousin marriage is shown to contain the same total information about linkage as a nuclear family with three affected children. Calculations show that it should be practical to map a recessive disease gene by studying DNA from fewer than a dozen unrelated, affected inbred children, given a complete RFLP linkage map. The method should make it possible to map many recessive diseases for which it is impractical or impossible to collect adequate numbers of families with multiple affected offspring.

  14. Infantile variant of Bartter syndrome and sensorineural deafness: A new autosomal recessive disorder

    SciTech Connect

    Landau, D.; Shalev, H.; Carmi, Rivka; Ohaly, M.

    1995-12-04

    The infantile variant of Bartter syndrome (IBS) is usually associated with maternal polyhydramnios, premature birth, postnatal polyuria and hypokalemic hypochloremic metabolic alkalosis and a typical appearance. IBS is thought to be an autosomal recessive trait. Several congenital tubular defects are associated with sensorineural deafness (SND). However, an association between the IBS and SND has not been reported so far. Here we describe 5 children of an extended consanguineous Bedouin family with IBS and SND. In 3 of the cases, the typical electrolyte imbalance and facial appearance were detected neonatally. SND was detected as early as age 1 month, suggesting either coincidental homozygotization of 2 recessive genes or a pleiotropic effect of one autosomal recessive gene. This association suggests that evaluation of SND is warranted in every case of IBS. 35 refs., 2 figs., 2 tabs.

  15. FOXE3 plays a significant role in autosomal recessive microphthalmia.

    PubMed

    Reis, Linda M; Tyler, Rebecca C; Schneider, Adele; Bardakjian, Tanya; Stoler, Joan M; Melancon, Serge B; Semina, Elena V

    2010-03-01

    FOXE3 forkhead transcription factor is essential to lens development in vertebrates. The eyes of Foxe3/foxe3-deficient mice and zebrafish fail to develop normally. In humans, autosomal dominant and recessive mutations in FOXE3 have been associated with variable phenotypes including anterior segment anomalies, cataract, and microphthalmia. We undertook sequencing of FOXE3 in 116 probands with a spectrum of ocular defects ranging from anterior segment dysgenesis and cataract to anophthalmia/microphthalmia. Recessive mutations in FOXE3 were found in four of 26 probands affected with bilateral microphthalmia (15% of all bilateral microphthalmia and 100% of consanguineous families with this phenotype). FOXE3-positive microphthalmia was accompanied by aphakia and/or corneal defects; no other associated systemic anomalies were observed in FOXE3-positive families. The previously reported c.720C > A (p.C240X) nonsense mutation was identified in two additional families in our sample and therefore appears to be recurrent, now reported in three independent microphthalmia families of varied ethnic backgrounds. Several missense variants were identified at varying frequencies in patient and control groups with some apparently being race-specific, which underscores the importance of utilizing race/ethnicity-matched control populations in evaluating the relevance of genetic screening results. In conclusion, FOXE3 mutations represent an important cause of nonsyndromic autosomal recessive bilateral microphthalmia.

  16. Autosomal recessive disorders among Arabs: an overview from Kuwait.

    PubMed

    Teebi, A S

    1994-03-01

    Kuwait has a cosmopolitan population of 1.7 million, mostly Arabs. This population is a mosaic of large and small minorities representing most Arab communities. In general, Kuwait's population is characterized by a rapid rate of growth, large family size, high rates of consanguineous marriages within the Arab communities with low frequency of intermarriage between them, and the presence of genetic isolates and semi-isolates in some extended families and Bedouin tribes. Genetic services have been available in Kuwait for over a decade. During this time it has become clear that Arabs have a high frequency of genetic disorders, and in particular autosomal recessive traits. Their pattern is unique and some disorders are relatively common. Examples are Bardet-Biedl and Meckel syndromes, phenylketonuria, and familial Mediterranean fever. A relatively large number of new syndromes and variants have been delineated in Kuwait's population, many being the result of homozygosity for autosomal recessive genes that occurred because of inbreeding. Some of these syndromes have subsequently been found in other parts of the world, negating the concept of the private syndrome. This paper provides an overview of autosomal recessive disorders among the Arabs in Kuwait from a personal perspective and published studies, and highlights the need for genetic services in Arab countries with the goal of prevention and treatment of genetic disorders.

  17. What Is a Recessive Allele?

    ERIC Educational Resources Information Center

    American Biology Teacher, 1991

    1991-01-01

    Presents four misconceptions students have concerning the concepts of recessive and dominant alleles. Discusses the spectrum of dominant-recessive relationships, different levels of analysis between phenotype and genotype, possible causes of dominance, and an example involving wrinkled peas. (MDH)

  18. Exploring Identity in Muslim Moroccan and Pakistani Immigrant Women

    PubMed Central

    Giuliani, Cristina; Tagliabue, Semira

    2015-01-01

    This study presents a qualitative investigation of how Muslim Moroccan and Pakistani female immigrants living in Italy conceptualize their cultural identity. Ten Moroccan and 10 Pakistani (adolescent and adult) women were interviewed through in-depth semi-structured interviews. The interviewees expressed a strong attachment to their culture of origin: their religion is a crucial aspect of their identity, along with certain cultural rules and traditional values. At the same time, both Moroccan and Pakistani participants were ambivalent toward and experienced difficulties in developing a connection to the host country, although the two groups exhibit their lack of connection to their host country in different ways: Moroccans’ self-representation is marked by a sense of foreignness and by a lack of an emotional connection with places where they are living while Pakistanis tend to express cultural distance and conflict with the host culture’s values. For both the Moroccan and Pakistani groups, the challenge of integration and biculturalism seems demanding in the Italian context and is marked by a deep feeling of emptiness, a lack of an emotional bond with the new country, and a strong cultural ambivalence. Finally, narrative themes are articulated across four interrelated dimensions (cultural, religious, gendered, spatial), revealing interesting differences based on national origin and generation. PMID:27247642

  19. Phenotypic variability of CLDN14 mutations causing DFNB29 hearing loss in the Pakistani population

    PubMed Central

    Bashir, Zil-e-Huma; Latief, Noreen; Belyantseva, Inna A.; Iqbal, Farheena; Riazuddin, S. Amer; Khan, Shaheen N.; Friedman, Thomas B.; Riazuddin, Sheikh; Riazuddin, Saima

    2013-01-01

    Human hereditary deafness at the DFNB29 autosomal locus on chromosome 21q22.1 is caused by recessive mutations of CLDN14, encoding claudin 14. This tight junction protein is tetra-membrane spanning that localizes to the apical tight junctions of organ of Corti hair cells and in many other tissues. Typically, the DFNB29 phenotype is characterized by pre-lingual, bi-lateral, sensorineural hearing loss. The goal of this study was to define the identity and frequency of CLDN14 mutations and associated inner ear phenotypes in a cohort of 800 Pakistani families segregating deafness. Hearing loss in 15 multi-generational families was found to co-segregate with CLDN14-linked STR markers. The sequence of the six exons and regions flanking the introns of CLDN14 in these 15 families revealed five likely pathogenic alleles. Two are novel missense substitutions (p.Ser87Ile and p.Ala94Val) while p.Arg81His, p.Val85Asp and p.Met133ArgfsX23 have been reported previously. Haplotype analyses indicate that p.Val85Asp and p.Met133ArgfsX23 are founder mutations. The p.Val85Asp accounts for approximately 67% of the mutant alleles of CLDN14 in our cohort. Combined with previously reported data, CLDN14 mutations were identified in 18 of 800 Pakistani families (2.25%; 95% CI, 1.4-3.5%). Hearing loss in the affected individuals homozygous for CLDN14 mutations varied from moderate to profound. This phenotypic variability may be due to environmental factors (e.g. drug and noise exposure) and/or genetic modifiers. PMID:23235333

  20. The frequency and effecting factors of consanguineous marriage in a group of soldiers in Ankara.

    PubMed

    Kir, Tayfun; Güleç, Mahir; Bakir, Bilal; Hoşjgönül, Esat; Tümerdem, Nazmi

    2005-07-01

    This cross-sectional study was carried out to investigate the frequency of consanguineous marriage in a group of army conscripts in Ankara and the factors affecting this. Of 4153 soldiers, 387 were married. The rate of marriage between first cousins was found to be 19.1%, and the overall rate of consanguineous marriage was 24.1%. Consanguineous marriage was found to be significantly prevalent among soldiers who were born in and still living in the Eastern region; among those who lived in villages; among those whose parents as well as themselves had low educational levels; and among those whose marriages were arranged by their families. Neither the payment of bride-price nor the presence of consanguinity between parents was a significant factor for consanguineous marriage. In addition, the age of the soldier and the age at marriage were significantly lower among soldiers married to first cousins than among soldiers whose marriages were not consanguineous.

  1. Demographic characteristics of the Israeli Arab community in connection with consanguinity.

    PubMed

    Jaber, L; Shohat, M; Halpern, G J

    1996-12-01

    In a previous nationwide survey of the Israeli Arab community we showed that 44% of all marriages are consanguineous. Further analysis of the data from this previous survey was undertaken, and we defined six demographic characteristics that may be associated with consanguinity or non-consanguinity in the marriages. Of these, we found a significant correlation (P <0.001) with religion (for Moslems, odds ratio 1.7), consanguinity in parents' marriages, and the respondent's attitude towards consanguineous marriage. The educational level achieved was not a major factor in the type of marriage chosen. These findings should enable us to plan specifically designed educational and counseling programs with a view to reducing the overall incidence of consanguineous marriage.

  2. The practice of consanguineous marriage in Oman: prevalence, trends and determinants.

    PubMed

    Islam, M Mazharul

    2012-09-01

    The practice of consanguineous marriage has been the culturally preferred form of marriage in most Arab and the Middle Eastern countries, including Oman, but due to a paucity of population-based data in the past there is a dearth of information about its form and dynamics in Oman. Recent national-level surveys allow this gap to be filled. This paper examines the prevalence, trends and determinants of consanguineous marriages in Oman using data from the 2000 Oman National Health Survey. The results indicate a very high prevalence of consanguineous marriage in Oman, as more than half (52%) of marriages are consanguineous. First cousin unions are the most common type of consanguineous unions, constituting 39% of all marriages and 75% of all consanguineous marriages. The study observed various patterns of consanguinity, some of them common with other Arab nations, and some unique in nature. Women's age at marriage, employment, place of childhood residence and geographical region appear to be significant determinants of consanguineous marriages. Consanguineous marriage shows a strong association with marital stability, early age at marriage and early-age childbearing. There has been no appreciable change in the prevalence of consanguineous unions in Oman over the last four decades despite massive socioeconomic development and modernization. However, recent marriage cohorts show slight declining trends. The results suggest that consanguinity is likely to remain stable in the future or decline at a slow rate. Specific health education and genetic counselling should be followed in line with WHO recommendations to minimize the negative health consequences of consanguinity for child health.

  3. Influence of parental consanguineous marriages on age at onset of bipolar disorder.

    PubMed

    Saadat, Mostafa

    2012-07-30

    The present study was performed to investigate the association between parental consanguineous marriages and age at onset of bipolar disorder (BPD). A total of 195 BPD patients participated in the study. Kaplan-Meier analysis revealed that relationships between age at onset and cumulative proportion of patients have different patterns with respect to types of parental marriages. Among early onset cases, the age at onset was higher for offspring of consanguineous than unrelated marriages, whereas in late onset cases the age at onset was lower for offspring of consanguineous than unrelated marriages. However, there was no difference between consanguineous and unrelated marriages for intermediate age at onset.

  4. Consanguinity Protecting Effect Against Breast Cancer among Tunisian Women: Analysis of BRCA1 Haplotypes.

    PubMed

    Medimegh, Imen; Troudi, Wafa; Omrane, Ines; Ayari, Hajer; Uhrhummer, Nancy; Majoul, Hamdi; Benayed, Farhat; Mezlini, Amel; Bignon, Yves-Jean; Sibille, Catherine; Elgaaied, Amel Benammar

    2015-01-01

    The purpose of this study is to assess the effect of consanguinity on breast cancer incidence in Tunisia. We conducted a case-control study to evaluate the involvement of heterozygote and homozygote haplotypes of BRCA1 gene SNPs according to consanguinity among 40 cases of familial breast cancer, 46 cases with sporadic breast cancer and 34 healthy controls. We showed significant difference in consanguinity rate between breast cancer patients versus healthy controls P = 0.001. Distribution of homozygous BRCA1 haplotypes among healthy women versus breast cancer patients was significantly different; p=0.02. Parental consanguinity seems to protect against breast cancer in the Tunisian population. PMID:25987085

  5. Mutations of the tyrosinase gene in Indo-Pakistani patients with type I (tyrosinase-deficient) oculocutaneous albinism (OCA).

    PubMed Central

    Tripathi, R K; Bundey, S; Musarella, M A; Droetto, S; Strunk, K M; Holmes, S A; Spritz, R A

    1993-01-01

    Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by deficient synthesis of melanin pigment. Type I (tyrosinase-deficient) OCA results from mutations of the tyrosinase gene (TYR gene) encoding tyrosinase, the enzyme that catalyzes the first two steps of melanin biosynthesis. Mutations of the TYR gene have been identified in a large number of patients, most of Caucasian ethnic origin, with various forms of type I OCA. Here, we present an analysis of the TYR gene in eight Indo-Pakistani patients with type I OCA. We describe four novel TYR gene mutations and a fifth mutation previously observed in a Caucasian patient. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:7902671

  6. Probable autosomal recessive inheritance of polysplenia, situs inversus and cardiac defects in an Amish family.

    PubMed

    Arnold, G L; Bixler, D; Girod, D

    1983-09-01

    We report on an Amish family with five individuals in two generations with complex congenital heart disease. Autopsy findings in one and clinical examination in the others support the diagnosis of polysplenia "syndrome." In a mouse model, this spectrum of situs abnormalities and cardiovascular defects shows recessive inheritance with homozygotes having either situs solitus or situs inversus or ambiguous situs. The parents of the four affected sibs are fourth cousins. We think that the father of these four children is an affected but clinically normal homozygote, that his deceased sister was an affected homozygote, and it seems likely that they too had consanguinous parents. PMID:6638068

  7. Entrepreneurial Attributes among Postgraduate Students of a Pakistani University

    ERIC Educational Resources Information Center

    Ali, Akhtar; Topping, Keith J.; Tariq, Riaz H.

    2010-01-01

    This paper explores entrepreneurial attributes among the students of The Islamia University of Bahawalpur, a public sector Pakistani university. Multistage sampling was employed to maximize the representation. Five hundred and twenty one master's level students from thirty departments returned completed questionnaires. Three factors emerged: self…

  8. Consanguineous marriages in the population of Sheikhupura (Punjab), Pakistan.

    PubMed

    Shami, S A; Iqbal, I

    1983-01-01

    This study was based on 1007 couples from the Sheikhupura population. The proportions of various parental relationships were: 0.3784 1st cousins, 0.0318 1st cousins once removed, 0.0784 double 2nd cousins, 0.1033 bradari distant relations, 0.3416 bradari, and 0.0665 unrelated parents. Mean paternal ages in unrelated couples are significantly higher than in 1st cousins, double 2nd cousins, and bradari relations. The differences in paternal and maternal ages are significantly higher in unrelated relations as compared to 1st cousins and double 2nd cousins. Procounced effects of consanguinity on parental deaths and neonatal deaths were observed in 1st cousin marriages compared to other relationships. Juvenile and infant deaths show comparatively less effects of consanguinity in 1st cousin marriages. Mean coefficient of inbreeding calculated for this population was 0.0271. Lethal gene equivalents calculated were 1.5424. The added risk of affected children in 1st cousins over that of unrelated parents was 4.82%. The results suggest that the deleterious genes show their effects more in the prenatal than in the postnatal period.

  9. An epidemiological study on consanguineous marriage among urban population in Alexandria.

    PubMed

    Mohamed, M S

    1995-01-01

    The study was carried out using a cross-sectional approach, involving interviews with 500 households randomly selected from three urban areas in Alexandria (Bab Sharki, El Gomrok and Karmouz). A questionnaire interview was conducted with married females in these households to determine prevalence of consanguineous marriages and to study knowledge of married females about causes and effects of consanguineous marriages. Prevalence of consanguineous marriages among 500 married females was 22.8% with the highest frequency among marriage between first cousins (15.8%). Average inbreeding coefficient up to the marriage between second cousins equals to 0.01172. The linear trend of consanguineous marriages throughout the last 50 years was statistically significant. Age at marriage was younger in consanguineous marriages than non consanguineous marriages. Longstanding familiarity and sharing same traditions and customs with male relatives were the main causes of consanguineous marriages. The majority of the studied females (42.2%) reported that consanguineous marriage is harmful while 29.6% reported that it has no effect on offsprings.

  10. Evidence for autosomal recessive inheritance of infantile dilated cardiomyopathy: studies from the Eastern Province of Saudi Arabia.

    PubMed

    Seliem, M A; Mansara, K B; Palileo, M; Ye, X; Zhang, Z; Benson, D W

    2000-12-01

    Familial dilated cardiomyopathy is being increasingly recognized, but affected individuals <10 y are rarely identified. We describe the natural history of dilated cardiomyopathy and evaluate the mode of inheritance among infants of Arab descent from the Eastern Province of Saudi Arabia. We evaluated 55 consecutive cases of dilated cardiomyopathy in patients <10 y of age seen during a 5-y interval. Echocardiography was the primary diagnostic modality. The 55 cases represented 20% of the offspring of 41 families of Arab descent. In 19 families (46%), parents were first cousins; there was no obvious consanguinity in 22 families (54%). Age at presentation was <30 mo (95%) (range, 1 to 100 mo); males (38%) and females (62%) were affected. Patients died (25 patients, 46%), improved (15 patients, 27%), or recovered (15 patients, 27%). The left ventricular shortening fraction at diagnosis ranged from 5 to 28% and did not differ in those who died, improved, or recovered. Complex segregation analysis of the family data using the mixed model of inheritance showed that a model of recessive inheritance best fits the data. Recessively inherited dilated cardiomyopathy has been infrequently reported, perhaps because it may be difficult to recognize in other patient groups in which consanguineous marriage is uncommon and the number of children per family is small. In the setting of consanguineous marriage, homozygosity mapping should lead to identification of the gene(s) causing dilated cardiomyopathy in the families we studied.

  11. An Estimate of the Average Number of Recessive Lethal Mutations Carried by Humans

    PubMed Central

    Gao, Ziyue; Waggoner, Darrel; Stephens, Matthew; Ober, Carole; Przeworski, Molly

    2015-01-01

    The effects of inbreeding on human health depend critically on the number and severity of recessive, deleterious mutations carried by individuals. In humans, existing estimates of these quantities are based on comparisons between consanguineous and nonconsanguineous couples, an approach that confounds socioeconomic and genetic effects of inbreeding. To overcome this limitation, we focused on a founder population that practices a communal lifestyle, for which there is almost complete Mendelian disease ascertainment and a known pedigree. Focusing on recessive lethal diseases and simulating allele transmissions, we estimated that each haploid set of human autosomes carries on average 0.29 (95% credible interval [0.10, 0.84]) recessive alleles that lead to complete sterility or death by reproductive age when homozygous. Comparison to existing estimates in humans suggests that a substantial fraction of the total burden imposed by recessive deleterious variants is due to single mutations that lead to sterility or death between birth and reproductive age. In turn, comparison to estimates from other eukaryotes points to a surprising constancy of the average number of recessive lethal mutations across organisms with markedly different genome sizes. PMID:25697177

  12. Small operator outwits recession

    SciTech Connect

    Jackson, D.

    1982-12-01

    Explains how Rockcastle, Inc., one of the smallest surface coal mine operators in the West, maintains production during the recession by concentrating on short-term contracts and spot sales to industrial and commercial users. The mining company has selected well established coal brokers to market its product to users such as sugar beet and cement plants, a brewery, steel mill, utility, and a molybdenum mill. Rockcastle produces, on a two-shift schedule, about 1,200 tpd of coal with a total workforce of 20, or approximately 30 tons per manshift. A fleet of 4 scrapers, with dozer-assist in most cases, is capable of removing 5,000 to 6,000 cu yd of overburden and interburden per shift.

  13. The prevalence and correlates of consanguineous marriages in Yemen: similarities and contrasts with other Arab countries.

    PubMed

    Jurdi, Rozzet; Saxena, Prem C

    2003-01-01

    Using data on 9762 women from the 1997 Yemen Demographic and Maternal and Child Health Survey, this paper examines the prevalence and socioeconomic correlates of consanguineous marriages in Yemen. The results indicate that 40% of marriages are consanguineous, over 85% of which are between first cousins. The prevalence of consanguineous marriages appears to have increased over time, particularly for the last marriage cohort. As for socioeconomic correlates, the study confirms the inverse association between consanguineous marriages and women's education and occupation, age at marriage and economic status. However, no statistically significant difference in the prevalence of consanguinity has been found by place of residence and geographical region. Somewhat unexpected results have been obtained by husband's background characteristics, with higher educated men and those working in the modern sector of the economy being more likely to be married to cousins.

  14. Pathogenic mutations in TULP1 responsible for retinitis pigmentosa identified in consanguineous familial cases

    PubMed Central

    Ullah, Inayat; Kabir, Firoz; Iqbal, Muhammad; Gottsch, Clare Brooks S.; Naeem, Muhammad Asif; Assir, Muhammad Zaman; Khan, Shaheen N.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2016-01-01

    Purpose To identify pathogenic mutations responsible for autosomal recessive retinitis pigmentosa (arRP) in consanguineous familial cases. Methods Seven large familial cases with multiple individuals diagnosed with retinitis pigmentosa were included in the study. Affected individuals in these families underwent ophthalmic examinations to document the symptoms and confirm the initial diagnosis. Blood samples were collected from all participating members, and genomic DNA was extracted. An exclusion analysis with microsatellite markers spanning the TULP1 locus on chromosome 6p was performed, and two-point logarithm of odds (LOD) scores were calculated. All coding exons along with the exon–intron boundaries of TULP1 were sequenced bidirectionally. We constructed a single nucleotide polymorphism (SNP) haplotype for the four familial cases harboring the K489R allele and estimated the likelihood of a founder effect. Results The ophthalmic examinations of the affected individuals in these familial cases were suggestive of RP. Exclusion analyses confirmed linkage to chromosome 6p harboring TULP1 with positive two-point LOD scores. Subsequent Sanger sequencing identified the single base pair substitution in exon14, c.1466A>G (p.K489R), in four families. Additionally, we identified a two-base deletion in exon 4, c.286_287delGA (p.E96Gfs77*); a homozygous splice site variant in intron 14, c.1495+4A>C; and a novel missense variation in exon 15, c.1561C>T (p.P521S). All mutations segregated with the disease phenotype in the respective families and were absent in ethnically matched control chromosomes. Haplotype analysis suggested (p<10−6) that affected individuals inherited the causal mutation from a common ancestor. Conclusions Pathogenic mutations in TULP1 are responsible for the RP phenotype in seven familial cases with a common ancestral mutation responsible for the disease phenotype in four of the seven families. PMID:27440997

  15. Endoscopic Gastrocnemius Intramuscular Aponeurotic Recession

    PubMed Central

    Lui, Tun Hing

    2015-01-01

    Gastrocnemius aponeurotic recession is the surgical treatment for symptomatic gastrocnemius contracture. Endoscopic gastrocnemius recession procedures has been developed recently and reported to have fewer complications and better cosmetic outcomes. Classically, this is performed at the aponeurosis distal to the gastrocnemius muscle attachment. We describe an alternative endoscopic approach in which the intramuscular portion of the aponeurosis is released. PMID:26900563

  16. Fort Play Children Recreate Recess

    ERIC Educational Resources Information Center

    Powell, Mark

    2007-01-01

    Recess beckons well before it actually arrives. Its allure can be heard in children's lunchtime conversations as they discuss imaginary roles, plans, alliances and teams, with an obvious appetite for play and its unbounded possibility. For some children, recess provides the most important reasons to come to school. In team sports, games of chase…

  17. Neonatal diabetes mellitus and cerebellar hypoplasia/agenesis: report of a new recessive syndrome

    PubMed Central

    Hoveyda, N.; Shield, J.; Garrett, C.; Chong, W; Beardsall, K.; Bentsi-Enchill, E.; Mallya, H.; Thompson, M.

    1999-01-01

    Classical neonatal diabetes mellitus is defined as hyperglycaemia occurring within the first six weeks of life in term infants. Cerebellar agenesis is rare. We report three cases of neonatal diabetes mellitus, cerebellar hypoplasia/agenesis, and dysmorphism occurring within a highly consanguineous family. This constellation of abnormalities has not previously been described. Two of these cases are sisters and the third case is a female first cousin. The pattern of inheritance suggests this is a previously undescribed autosomal recessive disorder. Prenatal diagnosis of the condition in this family was possible by demonstration of the absence of the cerebellum and severe IUGR.


Keywords: cerebellar agenesis/hypoplasia; neonatal diabetes mellitus; dysmorphic features; autosomal recessive PMID:10507728

  18. Domestic violence and consanguineous marriages - perspective from Rawalpindi, Pakistan.

    PubMed

    Shaikh, M Ali; Kayani, A; Shaikh, I Ali

    2014-01-01

    Domestic violence is globally endemic and adversely impacts the health and economic well-being of women and society. This study used the standardized and validated assessment instrument "Woman Abuse Screening Tool" to study the prevalence of various forms of domestic violence among married women. The relationship between domestic violence and consanguineous marriage was studied using the chi-squared test. Cumulatively, 1010 married women were interviewed. Emotional abuse was the most commonly reported abuse, reported by 721 (71.4%) women as either often or sometimes, followed by sexual abuse and physical abuse, reported by 527 (52.2%) and 511 (50.6%) respectively. Being married to one's cousin did not protect married women from being abused either emotionally or physically by their husbands; thsi was statistically significant. There is a need for better understanding of the magnitude and scale of domestic violence in Pakistan by using standardized assessment tools for meaningful comparisons across different parts of the country over time.

  19. COL11A2 mutation associated with autosomal recessive Weissenbacher-Zweymuller syndrome: molecular and clinical overlap with otospondylomegaepiphyseal dysplasia (OSMED).

    PubMed

    Harel, Tamar; Rabinowitz, Ronen; Hendler, Netta; Galil, Aharon; Flusser, Hagit; Chemke, Juan; Gradstein, Libe; Lifshitz, Tova; Ofir, Rivka; Elbedour, Khalil; Birk, Ohad S

    2005-01-01

    Autosomal recessive Weissenbacher-Zweymuller syndrome (WZS) is a skeletal dysplasia characterized by rhizomelic dwarfism and severe hearing loss. Mutations in the COL11A2 gene have been implicated in causing the autosomal dominant form of this syndrome as well as non-ocular Stickler syndrome and the autosomal recessive syndrome otospondylomegaepiphyseal dysplasia (OSMED). In a consanguineous Bedouin tribe living in Southern Israel, five individuals affected by autosomal recessive WZS were available for genetic analysis. Homozygosity of a mutation in the COL11A2 gene was found in all affected individuals. This finding lends molecular support to the clinical notion that autosomal recessive WZS and OSMED are a single entity. PMID:15558753

  20. Consanguineous marriage and differentials in age at marriage, contraceptive use and fertility in Pakistan.

    PubMed

    Hussain, R; Bittles, A H

    1999-01-01

    Fertility rates in Pakistan have remained consistently high over the past three decades. While numerous studies have examined sociodemographic determinants, the role of biological factors, and particularly consanguinity, has received little attention, even though marriage between close biological relatives continues to be the norm in Pakistan. Reproductive behaviour among women in consanguineous (first cousin) and non-consanguineous unions was compared, using data from a 1995 study of multi-ethnic communities in Karachi and the 1990-91 Pakistan Demographic & Health Survey (PDHS). The results show that, although female age at first marriage has been gradually rising in both study samples, women in consanguineous unions married at younger ages and were less likely to use modern contraceptive methods. In the Karachi sample, women in first cousin unions experienced a higher mean number of pregnancies and also reported a higher mean number of children ever born (CEB). However, their mean number of surviving children did not differ from those born to women in non-consanguineous unions, implying higher prenatal and/or postnatal losses in couples related as first cousins. On the other hand, the PDHS showed both lower CEB values for women in consanguineous marriages and a lower number of surviving children. Given the continuing popularity of consanguineous marriage, these findings have important implications for future fertility reduction in Pakistan.

  1. Consanguinity as a determinant of reproductive behaviour and mortality in Pakistan.

    PubMed

    Bittles, A H; Grant, J C; Shami, S A

    1993-06-01

    To determine the prevalence of consanguineous marriages and estimate the effects of consanguinity on reproductive behaviour and mortality, household and hospital-based surveys were conducted in 11 cities in the Pakistan province of Punjab between 1979 and 1985. The 9520 women interviewed reported 44,474 pregnancies, with data collected on maternal and paternal ages at marriage, abortions/miscarriages, stillbirths and deaths in the first month, at 2-12 months and 2-8/10 years. Six categories of consanguineous marriage were included: double first cousin, first cousin, first cousin once removed/double second cousin, second cousin, bradari (brotherhood) and non-consanguineous. Marriages contracted between spouses related as second cousins or closer accounted for 50.3% of the total, equivalent to an average coefficient of kinship (alpha = sigma piFi) of 0.0280. Unions between close biological relatives were characterized by younger maternal and paternal ages at marriage and reduced spousal age difference, but a longer time to first delivery. Overall, they exhibited greater fertility than non-consanguineous couples. Antenatal and postnatal mortality were assessed by consanguinity and age interval. Consanguinity-associated deaths were consistently higher in the neonatal, infant and childhood periods. The consequences of these outcomes on the health of the present and future generations is assessed.

  2. Effects of consanguineous marriages on fertility among three endogamous groups of Andhra Pradesh.

    PubMed

    Reddy, P G

    1987-01-01

    To assess interrelationships between consanguineous marriage and fertility, 3 caste groups in Andhra Pradesh--the Desuri Kapu, an affluent agricultural caste; the Devanga, an artisan caste in the middle range of the hierarchy; and the Mala, a scheduled caste at the bottom--were selected for field study. Consanguineous marriages are an essential part of the social structure in this area of southern India. A total of 2524 marriages were analyzed, of which 46% were consanguineous. 19% of consanguineous marriages were between uncle and niece, 22% were between 1st cousins, and 5% were between more distant cousins. The Devanga had the highest rate of related marriages (48%), followed by the Desuri Kapu (47%) and the Mala (41%). Higher caste individuals, and wealthier persons within each caste, are more likely to marry relatives so they can avoid splitting their properties through dowry of bride price. The consanguineous unions as a whole were significantly more fertile than nonconsanguineous unions. The mean number of pregnancies, live births, and surviving offspring was 4.85, 4.44, and 2.99, respectively, among consanguineous couples compared with 3.41, 3.32, and 2.87, respectively, among nonconsanguineous couples. Although the number of pregnancies and live births was significantly higher among consanguineous couples in all 3 castes compared with nonconsanguineous couples, the difference in the number of surviving children between consanguineous and nonconsanguineous unions was not significant among the wealthier castes. This suggests that child mortality is higher among the offspring of consanguineous unions, despite their greater wealth.

  3. Is there a significant trend in prevalence of consanguineous marriage in Tehran? A review of three generations.

    PubMed

    Akrami, Seyed Mohammad; Montazeri, Vahideh; Shomali, Somaieh Rashid; Heshmat, Ramin; Larijani, Bagher

    2009-02-01

    Consanguineous marriage is a common practice in Iran. The present study surveyed the trend in consanguineous marriage across three generations of Iranians. Index cases, consisting of 400 individuals attending the diabetes and osteoporosis clinic in Shariati Hospital, were interviewed. Data on consanguinity status for 1789 marriages within the index cases' families were obtained. Generation 1 consisted of marriages contracted before 1948, Generation 2 consisted of marriages contracted between 1949 and 1978, and Generation 3 consisted of marriages contracted after 1979. Prevalence of consanguineous marriage within these three generations was 8.8%, 16.6% and 19%, respectively, and represented a significant trend (p < 0.001). First cousin marriage was the most common type of consanguinity (69%). Socioeconomic level of families was not significantly related to having a consanguineous marriage. These data suggest that premarital genetic counseling and mass media efforts are needed to increase public awareness about genetic risks associated with consanguineous marriage.

  4. The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome

    PubMed Central

    Sheridan, Molly B.; Wohler, Elizabeth; Batista, Denise A. S.; Applegate, Carolyn; Hoover-Fong, Julie

    2015-01-01

    Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome. DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism. DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions of DCAF17 in the proband revealed homozygosity for a previously described founder mutation (c.436delC). Targeted DCAF17 sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified. PMID:26664771

  5. A Homozygous TPO Gene Duplication (c.1184_1187dup4) Causes Congenital Hypothyroidism in Three Siblings Born to a Consanguineous Family.

    PubMed

    Cangul, Hakan; Aydin, Banu K; Bas, Firdevs

    2015-12-01

    Congenital hypothyroidism (CH) is the most common neonatal endocrine disease, and germ-line mutations in the TPO gene cause the inherited form of the disease. Our aim in this study was to determine the genetic basis of congenital hypothyroidism in three affected children coming from a consanguineous Turkish family. Because CH is usually inherited in autosomal recessive manner in consanguineous/multicase families, we adopted a two-stage strategy of genetic linkage studies and targeted sequencing of the candidate genes. First, we investigated the potential genetic linkage of the family to any known CH locus, using microsatellite markers, and then screened for mutations in linked-gene by conventional sequencing. The family showed potential linkage to the TPO gene and we detected a homozygous duplication (c.1184_1187dup4) in all cases. The mutation segregated with disease status in the family. This study confirms the pathogenicity of the c.1184_1187dup4 mutation in the TPO gene and helps establish a genotype/phenotype correlation associated with this mutation. It also highlights the importance of molecular genetic studies in the definitive diagnosis and accurate classification of CH. PMID:27617131

  6. Map of autosomal recessive genetic disorders in Saudi Arabia: concepts and future directions.

    PubMed

    Al-Owain, Mohammed; Al-Zaidan, Hamad; Al-Hassnan, Zuhair

    2012-10-01

    Saudi Arabia has a population of 27.1 million. Prevalence of many autosomal recessive disorders is higher than in other known populations. This is attributable to the high rate of consanguineous marriages (56%), the tribal structure, and large family size. Founder mutations have been recognized in many autosomal recessive disorders, many of which are overrepresented within certain tribes. On the other hand, allelic heterogeneity is also observed among common and rare autosomal recessive conditions. With the adoption of more advanced molecular techniques in the country in recent years in conjunction with international collaboration, the mapping of various autosomal recessive disorders has increased dramatically. Different genetic concepts pertinent to this highly inbred population are discussed here. Addressing such genetic disorders at the national level will become a cornerstone of strategic health care initiatives in the 21st century. Current efforts are hampered by many socio-cultural and health care related factors. Education about genetic diseases, establishment of a "national registry" and mutational database, and enhanced healthcare access are crucial for success of any preventative campaign. PMID:22903695

  7. Consanguinity and endogamy in the Netherlands: demographic and medical genetic aspects.

    PubMed

    Ten Kate, Leo P; Teeuw, Marieke E; Henneman, Lidewij; Cornel, Martina C

    2014-01-01

    This paper reviews what is currently known about the presence of consanguinity and endogamy in the Netherlands, in the past and today, and concludes with a discussion of medical genetic aspects. First geographic characteristics, the demographic history, the genetic make-up of the native population, legal aspects and the public opinion are reviewed. Then data on the prevalence of consanguinity in the native population are presented for marriages since 1840, followed by data on consanguineous marriages among immigrants from countries with a tradition of close-kin marriages. It is estimated that approximately 1% of at-risk consanguineous couples are referred to clinical genetic centres for prospective genetic counselling in the Netherlands. This picture will change dramatically if and when next-generation sequencing is introduced to identify couples at ≥ 25% risk prospectively. PMID:25060279

  8. Modernization or cultural maintenance: the practice of consanguineous marriage in Iran.

    PubMed

    Jalal Abbasi-Shavazi, Mohammad; McDonald, Peter; Hosseini-Chavoshi, Meimanat

    2008-11-01

    Consanguineous marriage has been the culturally preferred form of marriage in Iran. This paper examines the extent to which education, urbanization and changes in modes of economic production have affected the incidence of consanguineous marriage and attitudes towards consanguineous marriages. The 2002 Iran Fertility Transition Survey conducted in the four provinces of Gilan, Sistan and Baluchistan, Yazd and West Azarbaijan provides information on the degree of relationship of marriage partners from around 6550 ever-married women aged 15-49. Attitudinal data were also obtained. Overall, the level of marriage to biological relatives ranged from 23% in Gilan to 78% in Sistan and Baluchistan. The paper finds that the practice of marriage to biological relatives has remained surprisingly resilient in the face of modernizing influences and that ethnicity, province and area of residence remain important determinants. On the other hand, attitudes have shifted towards marriage with a non-relative. Anthropological research would illuminate the processes of consanguineous marriage in Iran.

  9. Consanguinity and endogamy in the Netherlands: demographic and medical genetic aspects.

    PubMed

    Ten Kate, Leo P; Teeuw, Marieke E; Henneman, Lidewij; Cornel, Martina C

    2014-01-01

    This paper reviews what is currently known about the presence of consanguinity and endogamy in the Netherlands, in the past and today, and concludes with a discussion of medical genetic aspects. First geographic characteristics, the demographic history, the genetic make-up of the native population, legal aspects and the public opinion are reviewed. Then data on the prevalence of consanguinity in the native population are presented for marriages since 1840, followed by data on consanguineous marriages among immigrants from countries with a tradition of close-kin marriages. It is estimated that approximately 1% of at-risk consanguineous couples are referred to clinical genetic centres for prospective genetic counselling in the Netherlands. This picture will change dramatically if and when next-generation sequencing is introduced to identify couples at ≥ 25% risk prospectively.

  10. Pakistani Students' Perceptions about Use of the Internet in Their Academic Activities

    ERIC Educational Resources Information Center

    Ali, Zarqa S.

    2014-01-01

    The aim of the study is to explore Pakistani university students' use of the Internet in their studies and their perceptions of online academic life. Findings show that Internet use for academic purposes has both positive and negative aspects. There is a gender difference in Pakistani students' perceptions about the use of the Internet…

  11. The Study of Workplace Learning and Performance Competencies among Pakistani Practitioners

    ERIC Educational Resources Information Center

    Sherwani, Naseem Saeed

    2010-01-01

    The purpose of this study was to investigate Pakistani Workplace Learning and Performance (WLP) practitioners' perceptions of the importance of WLP competencies at the present time and in the next five years. The goals were to: (1) identify and characterize a profile of Pakistani WLP practitioners; (2) analyze perceptions of the current and future…

  12. The Effect of Inbreeding on the Distribution of Compound Heterozygotes: A Lesson from Lipase H Mutations in Autosomal Recessive Woolly Hair/Hypotrichosis

    PubMed Central

    Petukhova, Lynn; Shimomura, Yutaka; Wajid, Muhammad; Gorroochurn, Prakash; Hodge, Susan E.; Christiano, Angela M.

    2009-01-01

    Autozygosity mapping in consanguineous families has proven to be a powerful method for identifying recessive disease genes. Using this technique with whole genome SNP data generated from low density mapping arrays, we previously identified two genes that underlie autosomal recessive woolly hair (ARWH/hypotrichosis; OMIM278150), specifically P2RY5 and Lipase H (LIPH). In the current study, we sought to identify a novel disease locus for ARWH/hypotrichosis by analyzing two large consanguineous families from Pakistan who had initially been excluded for mutations at either of these disease loci by haplotype analysis with microsatellite markers. A genome-wide analysis of 10 members from each of the two families failed to identify significant regions of autozygosity or linkage. Upon genotyping an additional 10 family members in one of the families, parametric linkage analysis identified a region on chromosome 3q27 with evidence for linkage (Z = 2.5). Surprisingly, this region contains the LIPH gene. Microsatellite markers located within the LIPH gene were used for haplotype analysis and demonstrated that not one, but two haplotypes were segregating with the phenotype in each of these families. DNA sequencing identified two distinct LIPH mutations (280_369dup90 and 659_660delTA). Each affected individual (n = 38) was either homozygous for one mutation (n = 7 and 16 respectively), or compound heterozygous (n = 15). A review of the literature identified several reports of compound heterozygotes in consanguineous families. Prompted by this finding, we derived the probability that a patient affected with a recessive disease is carrying two mutations at the disease locus. We suggest that the validity of the IBD assumption may be challenged in large consanguineous families. PMID:19365138

  13. Novel homozygous PANK2 mutation identified in a consanguineous Chinese pedigree with pantothenate kinase-associated neurodegeneration

    PubMed Central

    Li, Yan-Fang; Li, Hong-Fu; Zhang, Yan-Bin; Wu, Ji-Min

    2016-01-01

    Pantothenate kinase-associated neurodegeneration (PKAN) is a rare autosomal recessive neurodegenerative disorder resulting from pantothenate kinase 2 (PANK2) gene mutations. It is clinically characterized by early onset of extrapyramidal symptoms, with or without pigmentary retinopathy, optic atrophy and acanthocytosis. The specific radiographic appearance of PKAN is the eye-of-the-tiger sign. However, there are few studies regarding PKAN patients of Chinese Han ancestry. In the present study, a Chinese 20-year-old female with an 8-year history of unsteady walking and involuntary movements is described. Brain magnetic resonance imaging revealed eye-of-the-tiger sign. Following sequencing of PANK2, a novel homozygous c.863C>T (p.P288L) mutation was identified in the patient and heterozygous c.863C>T was identified in her consanguineous parents. The absence of this mutation in the 1000 Genomes database, The Exome Aggregation Consortium, and 200 controls demonstrated that this mutation was probably pathogenic for PKAN in this family. In addition, the PANK2 c.863C>T mutation was predicted to be deleterious by SIFT, disease causing by Mutation Taster and probably damaging by PolyPhen2. PMID:27446545

  14. A novel mutation in the C7orf11 gene causes nonphotosensitive trichothiodystrophy in a multiplex highly consanguineous kindred.

    PubMed

    Pode-Shakked, Ben; Marek-Yagel, Dina; Greenberger, Shoshana; Pode-Shakked, Naomi; Pras, Elon; Barzilai, Aviv; Yassin, Saeed; Sidi, Yechezkel; Anikster, Yair

    2015-12-01

    Trichothiodystrophy (TTD), also known as sulfur-deficient brittle hair syndrome, is a rare autosomal recessive multisystem disorder, which manifests with brittle hair, mental retardation, ichthyosis and decreased fertility. Mutations in the TTDN1 (C7orf11) gene have been shown to cause a nonphotosensitive type of trichothiodystrophy. We report of a 19 years old male, born to consanguineous parents of Arab-Muslim descent, who presented due to severe renal failure, but exhibited additional unique features, including developmental delay, mental retardation, splenomegaly, pancytopenia, hypogonadism and brittle hair. Following the clinical diagnosis of nonphotosensitive TTD, sequencing of the coding exons of C7orf11 was performed and revealed the patient to be homozygous for a novel c.505dupA mutation. As the severe renal failure following which the proband was referred to our care is not typically characteristic of this disorder, its significance is discussed. Molecular diagnosis of this highly affected family should enable genetic counseling and prenatal diagnosis for future pregnancies. PMID:26518168

  15. A novel frameshift mutation in FGA (c.1846 del A) leading to congenital afibrinogenemia in a consanguineous Syrian family.

    PubMed

    Levrat, Emmanuel; Aboukhamis, Imad; de Moerloose, Philippe; Farho, Jaafar; Chamaa, Sahar; Reber, Guido; Fort, Alexandre; Neerman-Arbez, Marguerite

    2011-03-01

    Congenital afibrinogenemia is a rare autosomal recessive coagulation disorder characterized essentially by bleeding symptoms, but miscarriages and, paradoxically, thromboembolic events can also occur. Most reported mutations leading to congenital afibrinogenemia are located in FGA encoding the fibrinogen A α-chain. In this study, we analysed 12 individuals from a consanguineous Syrian family with reduced or absent fibrinogen levels: those with fibrinogen levels around 1 g/l (n = 7) were found to be heterozygous for a novel frameshift mutation in FGA exon 5 (c.1846 del A) and those with undetectable fibrinogen levels (n = 5) were homozygous for the same mutation. This novel frameshift mutation is the most C-terminal causative FGA mutation identified to date in afibrinogenemic patients. The resulting aberrant Aα-chain (p.Thr616HisfsX32) is most likely synthesized, but is less efficiently assembled and/or secreted into the circulation given the phenotype of asymptomatic hypofibrinogenemia in heterozygous individuals and bleeding diathesis in homozygous individuals.

  16. Accelerating novel candidate gene discovery in neurogenetic disorders via whole-exome sequencing of prescreened multiplex consanguineous families.

    PubMed

    Alazami, Anas M; Patel, Nisha; Shamseldin, Hanan E; Anazi, Shamsa; Al-Dosari, Mohammed S; Alzahrani, Fatema; Hijazi, Hadia; Alshammari, Muneera; Aldahmesh, Mohammed A; Salih, Mustafa A; Faqeih, Eissa; Alhashem, Amal; Bashiri, Fahad A; Al-Owain, Mohammed; Kentab, Amal Y; Sogaty, Sameera; Al Tala, Saeed; Temsah, Mohamad-Hani; Tulbah, Maha; Aljelaify, Rasha F; Alshahwan, Saad A; Seidahmed, Mohammed Zain; Alhadid, Adnan A; Aldhalaan, Hesham; AlQallaf, Fatema; Kurdi, Wesam; Alfadhel, Majid; Babay, Zainab; Alsogheer, Mohammad; Kaya, Namik; Al-Hassnan, Zuhair N; Abdel-Salam, Ghada M H; Al-Sannaa, Nouriya; Al Mutairi, Fuad; El Khashab, Heba Y; Bohlega, Saeed; Jia, Xiaofei; Nguyen, Henry C; Hammami, Rakad; Adly, Nouran; Mohamed, Jawahir Y; Abdulwahab, Firdous; Ibrahim, Niema; Naim, Ewa A; Al-Younes, Banan; Meyer, Brian F; Hashem, Mais; Shaheen, Ranad; Xiong, Yong; Abouelhoda, Mohamed; Aldeeri, Abdulrahman A; Monies, Dorota M; Alkuraya, Fowzan S

    2015-01-13

    Our knowledge of disease genes in neurological disorders is incomplete. With the aim of closing this gap, we performed whole-exome sequencing on 143 multiplex consanguineous families in whom known disease genes had been excluded by autozygosity mapping and candidate gene analysis. This prescreening step led to the identification of 69 recessive genes not previously associated with disease, of which 33 are here described (SPDL1, TUBA3E, INO80, NID1, TSEN15, DMBX1, CLHC1, C12orf4, WDR93, ST7, MATN4, SEC24D, PCDHB4, PTPN23, TAF6, TBCK, FAM177A1, KIAA1109, MTSS1L, XIRP1, KCTD3, CHAF1B, ARV1, ISCA2, PTRH2, GEMIN4, MYOCD, PDPR, DPH1, NUP107, TMEM92, EPB41L4A, and FAM120AOS). We also encountered instances in which the phenotype departed significantly from the established clinical presentation of a known disease gene. Overall, a likely causal mutation was identified in >73% of our cases. This study contributes to the global effort toward a full compendium of disease genes affecting brain function.

  17. Dentinogenesis imperfecta associated with short stature, hearing loss and mental retardation: a new syndrome with autosomal recessive inheritance?

    PubMed

    Cauwels, R G E C; De Coster, P J; Mortier, G R; Marks, L A M; Martens, L C

    2005-08-01

    The follow-up history and oral findings in two brothers from consanguineous parents suggest that the association of dentinogenesis imperfecta (DI), delayed tooth eruption, mild mental retardation, proportionate short stature, sensorineural hearing loss and dysmorphic facies may represent a new syndrome with autosomal recessive inheritance. Histological examination of the dentin matrix of a permanent molar from one of the siblings reveals morphological similarities with defective dentinogenesis as presenting in patients affected with Osteogenesis Imperfecta (OI), a condition caused by deficiency of type I collagen. A number of radiographic and histological characteristics, however, are inconsistent with classical features of DI. These findings suggest that DI may imply greater genetical heterogeneity than currently assumed.

  18. Bilateral sensorineural deafness and hydrocephalus due to foramen of Monro obstruction in sibs: A newly described autosomal recessive disorder

    SciTech Connect

    Chudley, A.E.; McCullough, C.; McCullough, D.W.

    1997-01-31

    We identified a Canadian-Mennonite family in which a brother and sister have hydrocephalus due to obstruction at the foramen of Monro and profound bilateral sensorineural deafness. This appears to be a unique combination of anomalies and, to our knowledge, has not been reported previously. Both parents and a brother are phenotypically normal. The parents are second cousins. Thus, on the basis of consanguinity, affected sibs of both sexes, and in the absence of evidence for intrauterine infections or other adverse perinatal events, this syndrome is likely inherited in an autosomal recessive fashion. 37 refs., 5 figs.

  19. Consanguineous marriage in PR China: a study in rural Man (Manchu) communities.

    PubMed

    Wang, W; Qian, Cong; Bittles, A H

    2002-01-01

    Although there is a long history of consanguineous marriage in China, information on its prevalence is very limited. The Man (Qing) dynasty ruled China for over 250 years, but no consanguinity studies have been reported on this important population. The objective of the present investigation was to determine the present-day level of consanguineous marriage in the Man community, and to compare the data with existing consanguinity information on other Chinese populations. The study was conducted in a group of 11 rural Man communities in the north-eastern Chinese province of Liaoning. Household-based interviews were conducted by local staff on 513 couples, 418 of whom were Man with another 95 Man-Han inter-ethnic marriages. Basic pedigrees were constructed to determine the biological relationship between each set of spouses. Thirty of the 418 couples were in a consanguineous union, with a mean coefficient of inbreeding alpha = 0.0012. The small population sizes of the study may have contributed to the spatial variation in the patterns of inbreeding. Across generations there was a reduction in consanguineous marriages and an increase in inter-ethnic unions, which paralleled changes in civil marriage regulations.

  20. The relationship between consanguineous marriage and death in fetus and infants

    PubMed Central

    Mohammadi, Majid Mehr; Hooman, Heidar Ali; Afrooz, Gholam Ali; Daramadi, Parviz Sharifi

    2012-01-01

    Background: Given the high prevalence of consanguineous marriages in rural and urban areas of Iran, the aim of this study was to identify its role in increasing fetal and infant deaths. Materials ans Methods: This was a cross-sectional study in which 494 mothers with more than one exceptional child (mentally retarded and physically-dynamically disabled) or with normal children were selected based on multi-stage random sampling method. Data was gathered using the features of parents with more than one exceptional child questionnaire. The validity and reliability of this questionnaire was acceptable. Hierarchical log-linear method was used for statistical analysis. Results: Consanguineous marriage significantly increased the number of births of exceptional children. Moreover, there was a significant relation between the history of fetal/infant death and belonging to the group. There was a significant relation between consanguineous marriage and the history of fetal/infant death which means consanguineous marriage increased the prevalence of fetal/infant death in parents with exceptional children rather than in parents with normal children. Conclusions: The rate of fetal/infant death in exceptional births of consanguineous marriages was higher than that of non-consanguineous marriages. PMID:23626609

  1. Genetic analysis of consanguineous families presenting with congenital ocular defects.

    PubMed

    Ullah, Ehsan; Nadeem Saqib, Muhammad Arif; Sajid, Sundus; Shah, Neelam; Zubair, Muhammad; Khan, Muzammil Ahmad; Ahmed, Iftikhar; Ali, Ghazanfar; Dutta, Atanu Kumar; Danda, Sumita; Lao, Richard; Ling-Fung Tang, Paul; Kwok, Pui-Yan; Ansar, Muhammad; Slavotinek, Anne

    2016-05-01

    Anophthalmia and microphthalmia (A/M) are a group of rare developmental disorders that affect the size of the ocular globe. A/M may present as the sole clinical feature, but are also frequently found in a variety of syndromes. A/M is genetically heterogeneous and can be caused by chromosomal aberrations, copy number variations and single gene mutations. To date, A/M has been caused by mutations in at least 20 genes that show different modes of inheritance. In this study, we enrolled eight consanguineous families with A/M, including seven from Pakistan and one from India. Sanger and exome sequencing of DNA samples from these families identified three novel mutations including two mutations in the Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) gene, [c.1310_1311delAT; p.(Tyr437Trpfs*44) and c.964G > A; p.(Val322Met)] and a single missense mutation in Forkhead Box E3 (FOXE3) gene, [c.289A > G p.(Ile97Val)]. Additionally two previously reported mutations were identified in FOXE3 and in Visual System Homeobox 2 (VSX2). This is the first comprehensive study on families with A/M from the Indian subcontinent which provides further evidence for the involvement of known genes with novel and recurrent mutations.

  2. Parental responses to consanguinity and genetic disease in Saudi Arabia.

    PubMed

    Panter-Brick, C

    1991-01-01

    In-depth interviews of 36 Saudi families whose children suffered from neuro-metabolic disorders were conducted at a specialist hospital in Riyadh in order to examine parental understanding of disease and attitudes towards future births and consanguineous marriages. Parents had difficulty accepting a genetic explanation for diseases that did not affect all children at the time of birth; they also expressed religious or folk beliefs to account for illness. Coping behaviours included denial and resignation to the situation, divorce and remarriage. Some families adopted a cautious approach to cousin marriages and future births; this was significantly related to their education level, but not to previous infant deaths. Awareness of medical facts brought little emotional comfort to parents but allowed for preventive measures through screening adult carriers and identifying affected infants. This study presents new material from Saudi Arabia to strengthen current awareness that the range of religious beliefs, social attitudes and reproductive behaviours adopted by families in a society undergoing rapid change is of direct relevance to health care.

  3. Fryns syndrome in a girl born to consanguineous parents.

    PubMed

    Schwyzer, U; Briner, J; Schinzel, A

    1987-01-01

    An overweight female newborn with multiple congenital anomalies died shortly after birth. The parents were cousins. The following abnormal findings were noted: Broad, square-shaped head with flat nose, misshapen ears, cleft palate, receding chin, short neck with additional skinfolds, disproportionately short limbs, transverse palmar creases, distal digital hypoplasia with hypoplastic finger- and toenails. Autopsy disclosed a number of further malformations including: dysplasia of the hippocampus, atypical lobation of the lungs with cystic-adenomatoid malformation of the left upper lobe, malrotation of the intestine, bilateral cystic renal dysplasia, bilateral atretic ureters plus a right accessory hydroureter, hypoplastic urinary bladder, uterus and vagina duplex and elongated, partly cystic ovaries. The pattern of malformations in this girl is very similar to that of 7 previously reported patients including two sets of siblings and one instance of parental consanguinity. All patients died shortly after birth. For proper genetic counselling and for prenatal ultrasonographic diagnosis in a further pregnancy, it is important to recognize patients with the Fryns syndrome.

  4. Mutations of the tyrosinase gene produce autosomal recessive ocular albinism

    SciTech Connect

    King, R.A.; Summers, C.G.; Oetting, W.S.

    1994-09-01

    Albinism has historically been divided into ocular (OA) and oculocutaneous (OCA) types based on the presence or absence of clinically apparent skin and hair involvement in an individual with the ocular features of albinism. The major genes for OCA include the tyrosinase gene in OCA1 and the P gene in OCA2. X-linked and autosomal recessive OA have been described and the responsible genes have not been identified. We now present six Caucasian individuals who have the phenotype of autosomal recessive OA but who have OCA1 as shown by the presence of mutations of the tyrosinase. They had white or very light hair and white skin at birth, and cutaneous pigment developed in the first decade of life. At ages ranging from 1.5-23 years, hair color was dark blond to light brown. The skin had generalized pigment and well developed tan was present on the exposed arm and face skin of four. Iris pigment was present and iris translucency varied. Molecular analysis of the tyrosinase gene, using PCR amplification and direct di-deoxy sequencing showed the following mutations: E398Z/E398Q, P406S/g346a, R402E/T373K, ?/D383N, and H211N/T373K. The homozygous individual was not from a known consanguineous mating. T373K is the most common tyrosinase gene mutation in our laboratory. Three of these mutations are associated with a total loss of tyrosinase activity (g346a splice-site, T373K, and D383N), while four are associated with residual enzyme activity (H211N, R402E, E398Q, and P406S). These studies show that mutations of the tyrosinase gene can produce the phenotype of autosomal recessive OA in an individual who has normal amounts of cutaneous pigment and the ability to tan after birth. This extends the phenotypic range of OCA1 to normal cutaneous pigment after early childhood, and suggest that mutations of the tyrosinase gene account for a significant number of individuals with autosomal recessive OA.

  5. Objective hydrograph baseflow recession analysis

    NASA Astrophysics Data System (ADS)

    Thomas, Brian F.; Vogel, Richard M.; Famiglietti, James S.

    2015-06-01

    A streamflow hydrograph recession curve expresses the theoretical relationship between aquifer structure and groundwater outflow to a stream channel. That theoretical relationship is often portrayed empirically using a recession plot defined as a plot of ln(-dQ/dt) versus ln(Q), where Q is streamflow discharge. Such hydrograph recession plots are commonly used to estimate recession parameters, aquifer properties and for evaluating alternative hydrologic hypotheses. We introduce a comprehensive and objective approach to analyze baseflow recessions with innovations including the use of quantile regression, efficient and objective numerical estimation of dQ/dt, inclusion of groundwater withdrawals, and incorporation of seasonal effects. We document that these innovations when all combined, lead to significant improvements, over previous studies, in our ability to discern the theoretical behavior of stream aquifer systems. A case study reveals that our methodology enables us to reject the simple linear reservoir hypothesis of stream aquifer interactions for watersheds in New Jersey and results in improved correlations between low flow statistics and aquifer properties for those same watersheds.

  6. An exome sequencing strategy to diagnose lethal autosomal recessive disorders.

    PubMed

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-03-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0-4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies.

  7. An exome sequencing strategy to diagnose lethal autosomal recessive disorders

    PubMed Central

    Ellard, Sian; Kivuva, Emma; Turnpenny, Peter; Stals, Karen; Johnson, Matthew; Xie, Weijia; Caswell, Richard; Lango Allen, Hana

    2015-01-01

    Rare disorders resulting in prenatal or neonatal death are genetically heterogeneous. For some conditions, affected fetuses can be diagnosed by ultrasound scan, but this is not usually possible until mid-gestation. There is often limited fetal DNA available for investigation. We investigated a strategy for diagnosing autosomal recessive lethal disorders in non-consanguineous pedigrees with multiple affected fetuses. Exome sequencing was performed to identify genes where each parent is heterozygous for a rare non-synonymous-coding or splicing variant. Putative pathogenic variants were tested for cosegregation in affected fetuses and unaffected siblings. In eight couples of European ancestry, we found on average 1.75 genes (range 0–4) where both parents were heterozygous for rare potentially deleterious variants. A proof-of-principle study detected heterozygous DYNC2H1 variants in a couple whose five fetuses had short-rib polydactyly. Prospective analysis of two couples with multiple pregnancy terminations for fetal akinesia syndrome was performed and a diagnosis was obtained in both the families. The first couple were each heterozygous for a previously reported GLE1 variant, p.Arg569His or p.Val617Met; both were inherited by their two affected fetuses. The second couple were each heterozygous for a novel RYR1 variant, c.14130-2A>G or p.Ser3074Phe; both were inherited by their three affected fetuses but not by their unaffected child. Biallelic GLE1 and RYR1 disease-causing variants have been described in other cases with fetal akinesia syndrome. We conclude that exome sequencing of parental samples can be an effective tool for diagnosing lethal recessive disorders in outbred couples. This permits early prenatal diagnosis in future pregnancies. PMID:24961629

  8. A frameshift mutation in GRXCR2 causes recessively inherited hearing loss.

    PubMed

    Imtiaz, Ayesha; Kohrman, David C; Naz, Sadaf

    2014-05-01

    More than 360 million humans are affected with some degree of hearing loss, either early or later in life. A genetic cause for the disorder is present in a majority of the cases. We mapped a locus (DFNB101) for hearing loss in humans to chromosome 5q in a consanguineous Pakistani family. Exome sequencing revealed an insertion mutation in GRXCR2 as the cause of moderate-to-severe and likely progressive hearing loss in the affected individuals of the family. The frameshift mutation is predicted to affect a conserved, cysteine-rich region of GRXCR2, and to result in an abnormal extension of the C-terminus. Functional studies by cell transfections demonstrated that the mutant protein is unstable and mislocalized relative to wild-type GRXCR2, consistent with a loss-of-function mutation. Targeted disruption of Grxcr2 is concurrently reported to cause hearing loss in mice. The structural abnormalities in this animal model suggest a role for GRXCR2 in the development of stereocilia bundles, specialized structures on the apical surface of sensory cells in the cochlea that are critical for sound detection. Our results indicate that GRXCR2 should be considered in differential genetic diagnosis for individuals with early onset, moderate-to-severe and progressive hearing loss.

  9. Bombay blood group: Is prevalence decreasing with urbanization and the decreasing rate of consanguineous marriage

    PubMed Central

    Mallick, Sujata; Kotasthane, Dhananjay S.; Chowdhury, Puskar S.; Sarkar, Sonali

    2015-01-01

    Context: Bombay blood group although rare is found to be more prevalent in the Western and Southern states of India, believed to be associated with consanguineous marriage. Aims: To estimate the prevalence of the Bombay blood group (Oh) in the urban population of Puducherry. To find the effect of urbanization on consanguineous marriage and to establish whether consanguinity plays a part in the prevalence of Oh group. To compare Oh group prevalence with that of other neighboring states, where population is not predominantly urban. Settings and Design: This is a descriptive study in a tertiary care hospital in Puducherry, over a period of 6 years. Materials and Methods: All blood samples showing ‘O’ group were tested with anti-H lectin. Specialized tests like Adsorption Elution Technique, inhibition assay for determination of secretor status were performed on Oh positive cases. Any history of consanguineous marriage was recorded. Statistical Analysis Used: All variables were categorical variable and percentage and proportions were calculated manually. Results: Analysis of the results of 35,497 study subjects showed that the most common group was ‘O’ group constituting 14,164 (39.90%) of subjects. Only three “Oh” that is, Bombay phenotype (0.008%) were detected. Consanguinity was observed in two cases (66.66%). Conclusions: This study shows the prevalence of Bombay blood group representing the urban population of Puducherry, to be high (0.008%) and associated with consanguineous marriage (66.66%). Thus, consanguinity is still an important risk factor present, even in an urban population in Southern India. PMID:26420929

  10. Autosomal recessive primary microcephalies (MCPH).

    PubMed

    Kaindl, Angela M

    2014-07-01

    Autosomal recessive primary microcephaly (MCPH) is a genetically heterogeneous disease characterized by a pronounced reduction in volume of otherwise architectonical normal brains and intellectual deficit. Here, we summarize the genetic causes of MCPH types 1-12 known to date. PMID:24780602

  11. Algebra, Home Mortgages, and Recessions

    ERIC Educational Resources Information Center

    Mariner, Jean A. Miller; Miller, Richard A.

    2009-01-01

    The current financial crisis and recession in the United States present an opportunity to discuss relevant applications of some topics in typical first-and second-year algebra and precalculus courses. Real-world applications of percent change, exponential functions, and sums of finite geometric sequences can help students understand the problems…

  12. Firms Still Training Despite Recession

    ERIC Educational Resources Information Center

    Felstead, Alan; Green, Francis; Jewson, Nick

    2011-01-01

    It is commonly assumed that company training is one of the first casualties in times of recession. Falling recruitment, pressures to cut costs and a focus on short-term survival force businesses to put training on the backburner. Expecting the worst, the UK Commission for Employment and Skills (UKCES), the Confederation of British Industry (CBI)…

  13. MORM syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34.

    PubMed

    Hampshire, Daniel J; Ayub, Mohammed; Springell, Kelly; Roberts, Emma; Jafri, Hussain; Rashid, Yasmin; Bond, Jacquelyn; Riley, John H; Woods, C Geoffrey

    2006-05-01

    A consanguineous pedigree is described where 14 individuals are affected with a novel autosomal recessive disorder, which causes static moderate mental retardation, truncal obesity, a congenital nonprogressive retinal dystrophy and micropenis in males. We have tentatively named this condition MORM syndrome. It shows similarities to Bardet-Biedl syndrome and Cohen syndrome, but can be distinguished by clinical features; the age of onset and nonprogressive nature of the visual impairment, the lack of characteristic facies, skin or gingival infection, microcephaly, 'mottled retina', polydactyly and small penis without testicular anomalies. Furthermore, linkage to the known Bardet-Biedl (BBS1-8) and Cohen syndrome loci was excluded. Autozygosity mapping identified a single homozygous subtelomeric region shared by all affecteds on chromosome 9q34.3, with a maximum LOD score of 5.64. We believe this to be the first example of the identification of a subtelomeric recessive locus by autozygosity mapping.

  14. Sickness, dreams and moral selfhood among migrant Pakistani Muslims.

    PubMed

    Qureshi, Kaveri

    2010-12-01

    This paper draws from two years of fieldwork investigating the social course of illness among Pakistani Muslims in East London, exploring how chronic illness is communicated and negotiated in local worlds disrupted by migrancy. It examines episodic short stories about dreams, premonitions and uncanny coincidences that were prominent within the illness narratives of migrant Pakistani Muslims, recalling and throwing light on complex questions concerning subjective constructions of misfortune, the personal and social meanings of illness and the relationships between narrative and selfhood. The ethnography identifies a strong normative context of communication about ill health and bad news, within which revelation through the mode of the supernatural takes on added significance. Recurrent motifs in the dreams emphasize the connectedness between family members scattered across migratory contexts, and the reawakening of moral obligations in families. Whilst medical anthropology has understood descriptions of dreams and other uncanny experiences as 'subjunctivising tactics' serving to maintain alternative plots about the source and outcome of illness, in the Islamic context the narrating of supernatural encounters can have transformative effects, re-organising praxis and conferring legitimacy to certain forms of moral selfhood. The paper therefore argues that the notion of the 'subjunctive mode' imposes the analysts' own system of logic and that there is a need to understand the interpretive frameworks present in the illness narratives in their own terms.

  15. Antitumour and antioxidant potential of some selected Pakistani honeys.

    PubMed

    Noor, Nadia; Sarfraz, Raja Adil; Ali, Shaukat; Shahid, Muhammad

    2014-01-15

    Antitumour potential of honey is attributed to its excellent antioxidant activity which in turn depends on the geographical origin. The present study focuses on exploration of antioxidant and antitumour potential as well as total phenolic contents (TPC) of 58 Pakistani honeys involving spectrochemical techniques and potato disk assay. Agrobacterium tumefaciens was used to induce tumours in potato disks. All analysed honey samples exhibited 1.33±0.00-155.16±0.98mg/100g of TPC, 50% 2,2-diphenyl picryl hydrazyl (DPPH) inhibition, ⩾7.36±0.43-39.86±2.34mg/100g qurecitin equivalent antioxidant contents, ⩾13.69±0.91-65.50±1.37mg/100g ascorbic acid equivalent antioxidant contents, 64.65±0.43-1780.74±11.79mM ferric reducing antioxidant power and 60% peroxide inhibition. Antitumour activity observed for 43 natural and 10 commercial samples was ⩾20%. Two samples from Faisalabad region showed 87.50±5.50% and 79.00±5.56% antitumour activity which were reference standard. It was concluded that Pakistani honeys possessed excellent antioxidant and antitumour potential overall.

  16. Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome.

    PubMed

    Gai, Nan; Jiang, Chen; Zou, Yong-Yi; Zheng, Yu; Liang, De-Sheng; Wu, Ling-Qian

    2016-07-01

    Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder, which is characterized by congenital cataracts, cerebellar ataxia, progressive muscle weakness, and delayed psychomotor development. SIL1, which is located at 5q31.2, is the only gene known to cause MSS. Dandy-Walker syndrome (DWS) is defined by hypoplasia, upward rotation of the cerebellar vermis, and cystic dilation of the fourth ventricle; however, its genetic pathogeny remains unclear. Here, we report a Chinese consanguineous family with MSS and DWS. Whole exome sequencing identified a novel nonstop mutation in SIL1. Sanger sequencing revealed that the mutation was segregated in this family according to a recessive mode of inheritance. We found that the mutation changed a stop codon (TGA) to an arginine codon (CGA), and no in-frame termination codon in the 3' untranslated region (UTR) of SIL1 could be found. The mRNA levels of SIL1 were decreased by 56.6% and 37.5% in immortalized lymphoblasts of the patients respectively; the protein levels of SIL1 were substantially decreased. This case study is the first report on Chinese MSS patients, MSS complicated by DWS, and a nonstop mutation in SIL1. Our findings imply the pathogenetic association between DWS and MSS.

  17. Novel SIL1 nonstop mutation in a Chinese consanguineous family with Marinesco-Sjögren syndrome and Dandy-Walker syndrome.

    PubMed

    Gai, Nan; Jiang, Chen; Zou, Yong-Yi; Zheng, Yu; Liang, De-Sheng; Wu, Ling-Qian

    2016-07-01

    Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder, which is characterized by congenital cataracts, cerebellar ataxia, progressive muscle weakness, and delayed psychomotor development. SIL1, which is located at 5q31.2, is the only gene known to cause MSS. Dandy-Walker syndrome (DWS) is defined by hypoplasia, upward rotation of the cerebellar vermis, and cystic dilation of the fourth ventricle; however, its genetic pathogeny remains unclear. Here, we report a Chinese consanguineous family with MSS and DWS. Whole exome sequencing identified a novel nonstop mutation in SIL1. Sanger sequencing revealed that the mutation was segregated in this family according to a recessive mode of inheritance. We found that the mutation changed a stop codon (TGA) to an arginine codon (CGA), and no in-frame termination codon in the 3' untranslated region (UTR) of SIL1 could be found. The mRNA levels of SIL1 were decreased by 56.6% and 37.5% in immortalized lymphoblasts of the patients respectively; the protein levels of SIL1 were substantially decreased. This case study is the first report on Chinese MSS patients, MSS complicated by DWS, and a nonstop mutation in SIL1. Our findings imply the pathogenetic association between DWS and MSS. PMID:27106665

  18. Social structure and consanguinity in a French mountain Population (1550-1849).

    PubMed

    Rabino-Massa, Emma; Prost, Michel; Boëtsch, Gilles

    2005-04-01

    Sociocultural factors play a crucial role in the variation of consanguinity in a population. The choice of specific matrimonial strategies can favor the closure or opening of the group to the outside, whereas differential fertility affects the gene flow from one generation to another. In the present study we analyzed the role of socioprofessional groups in the maintenance of endogamy and consanguinity in a French Alpine valley: Vallouise in the Briançon area. In mountain environments, where the reproductive space is limited and quickly saturated, the autochthonous families adopt diversified matrimonial strategies. These marriage practices tend to prevent fragmentation of agricultural property. We analyzed the matrimonial behavior in the two main social groups of this population (décideurs and farmers) from 1550 to 1849. To better understand the behavior of the two social groups, we considered the two components of consanguinity, close and distant. Our study showed that the two groups had similar behavior regarding consanguinity. The way to prevent fragmentation of the patrimony was to choose a consanguineous spouse. This type of strategy inevitably leads to a high percentage of endogamy, which in this region of the Alps exceeded 90% through many centuries. PMID:16201137

  19. Consanguinity and its sociodemographic differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan.

    PubMed

    Jabeen, Nazish; Malik, Sajid

    2014-06-01

    Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe. PMID:25076667

  20. Profiling β Thalassemia Mutations in Consanguinity and Nonconsanguinity for Prenatal Screening and Awareness Programme.

    PubMed

    Kumar, Ravindra; Arya, Vandana; Agarwal, Sarita

    2015-01-01

    Mutation spectrum varies significantly in different parts and different ethnic groups of India. Social factors such as preference to marry within the community and among 1st degree relatives (consanguinity) play an important role in impeding the gene pool of the disease within the community and so in society by and large. The present paper discusses the role of consanguinity in profiling of beta thalassemia mutation, and thus the approach for prenatal screening and prevention based awareness programme. Clinically diagnosed 516 cases of beta thalassemia were screened at molecular level. A detailed clinical Proforma was recorded with the information of origin of the family, ethnicity, and consanguinity. The present study reports that subjects originating from Uttar Pradesh, Uttarakhand, Bihar, and Jharkhand have c.92+5G>C and c.124_127delTTCT mutation as the commonest mutation compared to the subjects hailing from Madhya Pradesh and Chhattisgarh and Nepal where sickle mutation was found more common. In 40 consanguineous unions more common and specific beta mutations with higher rate of homozygosity have been reported. This consanguinity-based data helps not only in deciding target oriented prenatal diagnostic strategies but also in objective based awareness programmes in prevention of thalassemia major birth. PMID:26576156

  1. Trends in the frequencies of consanguineous marriages in the Israeli Arab community.

    PubMed

    Jaber, L; Halpern, G J; Shohat, T

    2000-08-01

    To assess the trends in the frequency of consanguineous marriages in the Israeli Arab population in the last 40 years, we conducted a two-part study. For the first part, we re-analyzed data from a nationwide study carried out in 1992, and for the second part, we undertook a new survey in 1998 in four locations: Taibe, Tira, Kalansuwa and Kafr Bara. Data regarding the frequency of consanguineous marriage in these four locations for the years 1961-1985 was extracted from the original survey, and for the years 1986-1998, from new questionnaires. The frequency of consanguineous marriage was highest in the period 1961 1965 (50.6%), but by the period 1981-1985 it had decreased to 40.6%. Over the whole time span of the 1992 study, a significant decrease was observed between the periods 1961-1975 and 1976-1985 (p < 0.0001). In the four-location study, there was a significant decrease in the frequency of consanguineous marriage from 52.9%, in the period 1961-1970 to 32.8% in the period 1991-1998 (p = 0.0006). We conclude that the custom of consanguineous marriage in the studied population is still extremely high, and preventive measures should be taken to decrease its frequency and associated complications.

  2. Effects of consanguineous marriage on reproductive outcome in an Arab community in Israel.

    PubMed

    Jaber, L; Merlob, P; Gabriel, R; Shohat, M

    1997-12-01

    Intrafamilial marriage is favoured by the Arab community in Israel, almost all of whom live in villages populated by a few (< 20) founding families. A previous study in Taibe, a large Arab village located 30 km from Tel Aviv, showed a significantly high malformation rate among infants of consanguineous parents. The present study examines the reproductive consequences of parental consanguinity in 610 families from the same village, selected retrospectively through infants routinely seen in the local well baby clinic. All mothers were interviewed with regard to previous pregnancy outcomes, including abortions, stillbirths, and neonatal or infant deaths, as well as the degree of consanguinity. In addition, we analysed the anthropometric measurements of the probands. The incidence of infant deaths was significantly higher in the inbred group (p < 0.001). No significant increase in fetal loss between the inbred and outbred groups was observed. There were no differences in anthropometric features, except for a lower birth weight in the consanguineous group (p < 0.035). This study, combined with our previous studies of the same population, indicates a prominent public health problem associated with consanguineous marriage in the Arab community and a need for specific genetic counselling.

  3. Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions

    PubMed Central

    Shihab, Hashem A.; Rodriguez, Santiago; Gaunt, Tom R.; Day, Ian N.M.

    2016-01-01

    Summary Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome—even when completely “knocked out,” do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations “as a whole” can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient. PMID:27000383

  4. THE PREVALENCE OF CONSANGUINEOUS MARRIAGES AND AFFECTING FACTORS IN TURKEY: A NATIONAL SURVEY.

    PubMed

    Kaplan, Sena; Pinar, Gul; Kaplan, Bekir; Aslantekin, Filiz; Karabulut, Erdem; Ayar, Banu; Dilmen, Ugur

    2016-09-01

    This study was carried out by the Turkish Republic Ministry of Health to determine the prevalence of consanguineous marriage and its correlates with socio-demographic and obstetric risk factors in women in Turkey. The cross-sectional, national-level study was carried out from October to December 2013. The study population was composed of women between the ages of 15 and 65 years living in Turkey. The sample size was calculated as 9290 houses within Turkey's 81 provinces so as to improve the Turkish rural-urban expectations by means of systematic stack sampling according to the Turkish Statistical Institute's address-based vital statistics system. The target sample size was 6364, but only eligible 4913 women, who had been married, were included in the study. The consanguineous marriage frequency in the sample was found to be 18.5%, and of these 57.8% were first cousin marriages. Women living in an extended family and whose education level and first marriage ages were low, and whose perceived economic status was poor, had higher frequencies of consanguineous marriage (p<0.001). Consanguineous marriage frequencies were higher (p<0.001) for women who had spontaneous abortions and stillbirths or who had given birth to infants with a congenital abnormality. In this context, it is important to develop national policies and strategies to prevent consanguineous marriages in Turkey.

  5. Are consanguineous marriage and swaddling the risk factors of developmental dysplasia of the hip?

    PubMed

    Guner, Sukriye Ilkay; Guner, Savas; Peker, Erdal; Ceylan, Mehmet Fethi; Guler, Ayse; Turktas, Ugur; Kaki, Barıs

    2013-02-01

    The purpose of this study was to investigate prospectively the effects of swaddling and consanguineous marriage on developmental dysplasia of the hip and associated risk factors. We screened by ultrasound 265 infants using the Graf method. The Pediatrics Department referred all newborn infants with suspected instability or a recognized risk factor to the orthopedic clinic. Risk factors of developmental dysplasia of the hip were searched and noted in these patients. Swaddling and consanguineous marriage were also determined and noted. We observed 164 of 265 infants (61.9 %) who had been swaddled and that 64 of 265 infants' parents were in a consanguineous marriage (24.2 %). In the statistical analysis that was conducted for swaddling and consanguineous marriage, highly significant differences were found. Our study showed that the rate of developmental dysplasia of the hip is very high, 11.7 %, in our region, eastern Turkey. Also, we commonly see improper swaddling and consanguineous marriage in our region, which affects many infants.

  6. Consanguinity and its sociodemographic differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan.

    PubMed

    Jabeen, Nazish; Malik, Sajid

    2014-06-01

    Kashmiri population in the northeast of Pakistan has strong historical, cultural and linguistic affinities with the neighbouring populations of upper Punjab and Potohar region of Pakistan. However, the study of consanguineous unions, which are customarily practised in many populations of Pakistan, revealed marked differences between the Kashmiris and other populations of northern Pakistan with respect to the distribution of marriage types and inbreeding coefficient (F). The current descriptive epidemiological study carried out in Bhimber district of Mirpur division, Azad Jammu and Kashmir, Pakistan, demonstrated that consanguineous marriages were 62% of the total marriages (F=0.0348). First-cousin unions were the predominant type of marriages and constituted 50.13% of total marital unions. The estimates of inbreeding coefficient were higher in the literate subjects, and consanguinity was witnessed to be rising with increasing literacy level. Additionally, consanguinity was observed to be associated with ethnicity, family structure, language, and marriage arrangements. Based upon these data, a distinct sociobiological structure, with increased stratification and higher genomic homozygosity, is expected for this Kashmiri population. In this communication, we present detailed distribution of the types of marital unions and the incidences of consanguinity and inbreeding coefficient (F) across various sociodemographic strata of Bhimber/Mirpuri population. The results of this study would have implication not only for other endogamous populations of Pakistan but also for the sizeable Kashmiri community immigrated to Europe.

  7. Ethnic disparity in 21-hydroxylase gene mutations identified in Pakistani congenital adrenal hyperplasia patients

    PubMed Central

    2011-01-01

    Background Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders caused by defects in the steroid 21 hydroxylase gene (CYP21A2). We studied the spectrum of mutations in CYP21A2 gene in a multi-ethnic population in Pakistan to explore the genetics of CAH. Methods A cross sectional study was conducted for the identification of mutations CYP21A2 and their phenotypic associations in CAH using ARMS-PCR assay. Results Overall, 29 patients were analyzed for nine different mutations. The group consisted of two major forms of CAH including 17 salt wasters and 12 simple virilizers. There were 14 phenotypic males and 15 females representing all the major ethnic groups of Pakistan. Parental consanguinity was reported in 65% cases and was equally distributed in the major ethnic groups. Among 58 chromosomes analyzed, mutations were identified in 45 (78.6%) chromosomes. The most frequent mutation was I2 splice (27%) followed by Ile173Asn (26%), Arg 357 Trp (19%), Gln319stop, 16% and Leu308InsT (12%), whereas Val282Leu was not observed in this study. Homozygosity was seen in 44% and heterozygosity in 34% cases. I2 splice mutation was found to be associated with SW in the homozygous. The Ile173Asn mutation was identified in both SW and SV forms. Moreover, Arg357Trp manifested SW in compound heterozygous state. Conclusion Our study showed that CAH exists in our population with ethnic difference in the prevalence of mutations examined. PMID:21329531

  8. A novel homozygous mutation in HSF4 causing autosomal recessive congenital cataract.

    PubMed

    Behnam, Mahdiyeh; Imagawa, Eri; Chaleshtori, Ahmad Reza Salehi; Ronasian, Firooze; Salehi, Mansoor; Miyake, Noriko; Matsumoto, Naomichi

    2016-02-01

    Cataract is defined as opacity in the crystalline lens and congenital cataract occurs during the first year of life. Until now, mutations of more than 50 genes in congenital cataract have been reported with various modes of inheritance. Among them, HSF4 mutations have been reported in autosomal dominant, autosomal recessive and age-related forms of cataract. The inheritance patterns of these mutations depend on their mutational positions in HSF4: autosomal dominant or recessive mutations are respectively found either in a DNA-binding domain or in (or downstream of) hydrophobic repeats. Here we report a novel homozygous HSF4 mutation (c.521T>C, p.Leu174Pro) in two affected sibs of an Iranian consanguineous family using whole exome sequencing. The mutation is predicted as highly pathogenic by in silico analysis (SIFT, Polyphen2 and MutationTaster) and is not found in any of control databases. This mutation is located in a hydrophobic repeat of the HSF4 protein, which is consistent with the mode of inheritance as an autosomal recessive trait. PMID:26490182

  9. Novel mutations in the genes TGM1 and ALOXE3 underlying autosomal recessive congenital ichthyosis

    PubMed Central

    Ullah, Rahim; Ansar, Muhammad; Durrani, Zaka Ullah; Lee, Kwanghyuk; Santos-Cortez, Regie Lyn P.; Muhammad, Dost; Ali, Mahboob; Zia, Muhammad; Ayub, Muhammad; Khan, Suliman; Smith, Josh D.; Nickerson, Deborah A.; Shendure, Jay; Bamshad, Michael; Leal, Suzanne M.; Ahmad, Wasim

    2016-01-01

    Background Ichthyoses are clinically characterized by scaling or hyperkeratosis of the skin or both. It can be an isolated condition limited to the skin or appear secondarily with involvement of other cutaneous or systemic abnormalities. Methods The present study investigated clinical and molecular characterization of three consanguineous families (A, B, C) segregating two different forms of autosomal recessive congenital ichthyosis (ARCI). Linkage in three consanguineous families (A, B, C) segregating two different forms of ARCI was searched by typing microsatellite and single nucleotide polymorphism marker analysis. Sequencing of the two genes TGM1 and ALOXE3 was performed by the dideoxy chain termination method. Results Genome-wide linkage analysis established linkage in family A to TGM1 gene on chromosome 14q11 and in families B and C to ALOXE3 gene on chromosome 17p13. Subsequently, sequencing of these genes using samples from affected family members led to the identification of three novel mutations: a missense variant p.Trp455Arg in TGM1 (family A); a nonsense variant p.Arg140* in ALOXE3 (family B); and a complex rearrangement in ALOXE3 (family C). Conclusion The present study further extends the spectrum of mutations in the two genes involved in causing ARCI. Characterizing the clinical spectrum resulting from mutations in the TGM1 and ALOXE3 genes will improve diagnosis and may direct clinical care of the family members. PMID:26578203

  10. Differences in Physical Activity during School Recess

    ERIC Educational Resources Information Center

    Ridgers, Nicola D.; Saint-Maurice, Pedro F.; Welk, Gregory J.; Siahpush, Mohammad; Huberty, Jennifer

    2011-01-01

    Background: School recess provides a daily opportunity for physical activity engagement. The purpose of this study was to examine physical activity levels during recess by gender, ethnicity, and grade, and establish the contribution of recess to daily school physical activity levels. Methods: Two hundred and ten children (45% boys) from grades 3…

  11. An empirical analysis of the effects of consanguineous marriages on economic development.

    PubMed

    Bildirici, Melike; Kökdener, Meltem; Ersin, Oezgür ömer

    2010-01-01

    In this study, development experiences toward economic development are investigated to provide an alternative analysis of economic development, human capital, and genetic inheritance in the light of consanguineous marriages. The countries analyzed in the study are discussed in accordance with consanguineous marriage practices and classified by their per capita gross domestic product (GDP) growth. A broad range of countries are analyzed in the study. Arab countries that experienced high rates of growth in their gross national income during the twentieth century but failed to fulfill adequate development measures as reflected in the growth in national income, countries undergoing transition from tight government regulation to free market democracy, and African nations that have experienced complications in the process of development show important differences in the process of economic development. It is shown that the countries that have reached high average development within the context of per capita GDP have overcome problems integral to consanguineous marriage.

  12. New Recessive Syndrome of Microcephaly, Cerebellar Hypoplasia, and Congenital Heart Conduction Defect

    PubMed Central

    Zaki, Maha S; Salam, Ghada M H Abdel; Saleem, Sahar N; Dobyns, William B; Issa, Mahmoud Y; Sattar, Shifteh; Gleeson, Joseph G

    2011-01-01

    We identified a two-branch consanguineous family in which four affected members (three females and one male) presented with constitutive growth delay, severe psychomotor retardation, microcephaly, cerebellar hypoplasia, and second-degree heart block. They also shared distinct facial features and similar appearance of their hands and feet. Childhood-onset insulin-dependent diabetes mellitus developed in one affected child around the age of 9 years. Molecular analysis excluded mutations in potentially related genes such as PTF1A, EIF2AK3, EOMES, and WDR62. This condition appears to be unique of other known conditions, suggesting a unique clinical entity of autosomal recessive mode of inheritance. © 2011 Wiley Periodicals, Inc. PMID:22002884

  13. [A case of autosomal recessive hypomyelinating leukodystrophy without GJA12 mutation presenting a novel phenotype].

    PubMed

    Ishikawa, Tomoko; Sato, Kimiko; Shimazaki, Rie; Goto, Katsumasa; Matsuda, Takao; Ishiura, Hiroyuki

    2010-01-01

    A 50-year-old woman, who had consanguineous parents, developed gait disturbance at age 3, and revealed nystagmus, cerebellar ataxia, peripheral neuropathy, and spastic tetraparesis. She admitted to our hospital at age 14, and the symptoms progressed very slowly. MRI of this case at age 45 showed a remarkable, diffuse hypomyelination of the cerebrum. Her older sister who already deceased at age 16 showed neurological symptoms similar to this case. The patient was found to have no proteolipid protein-1 gene duplications and deletions and base substitution. Her symptoms were considered to be different from those of typical HLD2, 3, 4 and 5. She carried no GJA12 mutations. These facts suggested that this disease is a novel, autosomal recessive hypomyelinating leukodystrophy. PMID:20120347

  14. Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping

    SciTech Connect

    Kruglyak, L.; Daly, M.J.; Lander, E.S. |

    1995-02-01

    Homozygosity mapping is a powerful strategy for mapping rare recessive traits in children of consanguineous marriages. Practical applications of this strategy are currently limited by the inability of conventional linkage analysis software to compute, in reasonable time, multipoint LOD scores for pedigrees with inbreeding loops. We have developed a new algorithm for rapid multipoint likelihood calculations in small pedigrees, including those with inbreeding loops. The running time of the algorithm grows, at most, linearly with the number of loci considered simultaneously. The running time is not sensitive to the presence of inbreeding loops, missing genotype information, and highly polymorphic loci. We have incorporated this algorithm into a software package, MAPMAKER/HOMOZ, that allows very rapid multipoint mapping of disease genes in nuclear families, including homozygosity mapping. Multipoint analysis with dozens of markers can be carried out in minutes on a personal workstation. 23 refs., 4 figs., 1 tab.

  15. The changing pattern of consanguinity in a selected region of the Israeli Arab community.

    PubMed

    Sharkia, Rajach; Zaid, Muhamad; Athamna, Abed; Cohen, Dani; Azem, Abdussalam; Zalan, Abdelnaser

    2008-01-01

    The prevalence of consanguinity within the Israeli Arab community is relatively high, and is associated with high rates of inherited disorders that lead to a high frequency of morbidity and mortality. Data on consanguinity between couples were recorded during two periods (1980-1985 and 2000-2004) in relation to socioeconomic status of 4 selected villages. Two of the villages (A and B) are known to have high socioeconomic status, and the other two (C and D) are known to have low socioeconomic status. The average incidence of consanguineous marriages has slightly decreased from 33.1% in the first period to 25.9% in the second period (P = 0.0218) in all of the 4 villages. Marriages between first cousins showed a more significant decrease, from 23.9% in the first period to 13.6% in the second period (P < 0.0001). The average consanguinity rates of villages A and B were found to decrease from 22.3 to 16.2% respectively (P < 0.001) between the two observation periods, whereas those of villages C and D were found to decrease from 42.3 to 37.2%, (P < 0.001) during the same two periods. Thus, there has been a change in the pattern of consanguinity within the selected Israeli Arab villages, between the two study periods. This change seems to correlate with the sociodemographic status of the villages. Therefore, improving the socioeconomic status of the villages, as well as implementation of proper health education programs, is expected to have a positive effect in reducing consanguinity.

  16. Molecular genetics of MARVELD2 and clinical phenotype in Pakistani and Slovak families segregating DFNB49 hearing loss

    PubMed Central

    Nayak, Gowri; Varga, Lukas; Trincot, Claire; Shahzad, Mohsin; Friedman, Penelope L.; Klimes, Iwar; Greinwald, John H.; Riazuddin, S Amer; Masindova, Ivica; Profant, Milan; Khan, Shaheen N.; Friedman, Thomas B.; Ahmed, Zubair M.; Gasperikova, Daniela; Riazuddin, Sheikh; Riazuddin, Saima

    2015-01-01

    Pathogenic mutations of MARVELD2, encoding tricellulin, a tricelluar tight junction protein, cause autosomal recessive non-syndromic hearing loss (DFNB49) in families of Pakistan and Czech Roma origin. In fact, they are a significant cause of prelingual hearing loss in the Czech Roma, second only to GJB2 variants. Previously, we reported that mice homozygous for p.Arg497* variant of Marveld2 had a broad phenotypic spectrum, where defects were observed in the inner ear, heart, mandibular salivary gland, thyroid gland and olfactory epithelium. The current study describes the types and frequencies of MARVELD2 alleles and clinically reexamines members of DFNB49 families. We found that MARVELD2 variants are responsible for about 1.5% (95% CI: 0.8 – 2.6) of non-syndromic hearing loss in our cohort of 800 Pakistani families. The c.1331+2T>C allele is recurrent. In addition, we identified a novel large deletion in a single family, which appears to have resulted from non-allelic homologous recombination between two similar Alu short interspersed elements. Finally, we observed no other clinical manifestations co-segregating with hearing loss in DFNB49 human families, and hypothesize that the additional abnormalities in the Marveld2 mutant mouse indicates a critical non-redundant function for tricellulin in other organ systems. PMID:25666562

  17. Are streamflow recession characteristics really characteristic?

    NASA Astrophysics Data System (ADS)

    Stoelzle, M.; Stahl, K.; Weiler, M.

    2013-02-01

    Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage-outflow relationship based on the dQ/dt-Q method. Such recession analysis methods (RAMs) are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how comparably the resulting recession models distinguish characteristic catchment behavior. In this study we combined three established recession extraction methods with three different parameter-fitting methods to the power-law storage-outflow model to compare the range of recession characteristics that result from the application of these different RAMs. Resulting recession characteristics including recession time and corresponding storage depletion were evaluated for 20 meso-scale catchments in Germany. We found plausible ranges for model parameterization; however, calculated recession characteristics varied over two orders of magnitude. While recession characteristics of the 20 catchments derived with the different methods correlate strongly, particularly for the RAMs that use the same extraction method, not all rank the catchments consistently, and the differences among some of the methods are larger than among the catchments. To elucidate this variability we discuss the ambiguous roles of recession extraction procedures and the parameterization of the storage-outflow model and the limitations of the presented recession plots. The results suggest strong limitations to the comparability of recession characteristics derived with different methods, not only in the model parameters but also in the relative characterization of different catchments. A multiple-methods approach to investigating streamflow recession characteristics should be considered for applications

  18. Are streamflow recession characteristics really characteristic?

    NASA Astrophysics Data System (ADS)

    Stoelzle, M.; Stahl, K.; Weiler, M.

    2012-09-01

    Streamflow recession has been investigated by a variety of methods, often involving the fit of a model to empirical recession plots to parameterize a non-linear storage-outflow relationship. Such recession analysis methods (RAMs) are used to estimate hydraulic conductivity, storage capacity, or aquifer thickness and to model streamflow recession curves for regionalization and prediction at the catchment scale. Numerous RAMs have been published, but little is known about how characteristic the resulting recession models are to distinguish characteristic catchment behavior. In this study we combined three established recession extraction methods with three different parameter-fitting methods to the power-law storage-outflow model to compare the range of recession characteristics that result from the application of these different RAMs. Resulting recession characteristics including recession time and corresponding storage depletion were evaluated for 20 meso-scale catchments in Germany. We found plausible ranges for model parameterization, however, calculated recession characteristics varied over two orders of magnitude. While recession characteristics of the 20 catchments derived with the different methods correlate strongly, particularly for the RAMs that use the same extraction method and while they rank the catchments relatively consistent, there are still considerable differences among the methods. To elucidate this variability we discuss the ambiguous roles of recession extraction procedures and the parameterization of storage-outflow model and the limitations of the presented recession plots. The results suggest strong limitations to the comparability of recession characteristics derived with different methods, not only in the model parameters but also in the relative characterization of different catchments. A multiple methods approach to investigate streamflow recession characteristics should be considered for applications whenever possible.

  19. CHARACTERIZING THE SPECTRUM OF AUTOSOMAL RECESSIVE HEREDITARY HEARING LOSS IN IRAN

    PubMed Central

    Sloan-Heggen, Christina M; Babanejad, Mojgan; Beheshtian, Maryam; Simpson, Allen C; Booth, Kevin T; Ardalani, Fariba; Frees, Kathy L; Mohseni, Marzieh; Mozafari, Reza; Mehrjoo, Zohreh; Jamali, Leila; Vaziri, Saeideh; Akhtarkhavari, Tara; Bazazzadegan, Niloofar; Nikzat, Nooshin; Arzhangi, Sanaz; Sabbagh, Farahnaz; Otukesh, Hasan; Seifati, Seyed Morteza; Khodaei, Hossein; Taghdiri, Maryam; Meyer, Nicole C; Daneshi, Ahmad; Farhadi, Mohammad; Kahrizi, Kimia; Smith, Richard JH; Azaiez, Hela; Najmabadi, Hossein

    2016-01-01

    Background Countries with culturally accepted consanguinity provide a unique resource for the study of rare recessively inherited genetic diseases. Although hereditary hearing loss (HHL) is not uncommon, it is genetically heterogeneous, with over 85 genes causally implicated in non-syndromic hearing loss (NSHL). This heterogeneity makes many gene-specific types of NSHL exceedingly rare. We sought to define the spectrum of autosomal recessive HHL in Iran by investigating both common and rarely diagnosed deafness-causing genes. Design Using a custom targeted genomic enrichment (TGE) panel we simultaneously interrogating all known genetic causes of NSHL in a cohort of 302 GJB2-negative Iranian families. Results We established a genetic diagnosis for 67% of probands and their families, with over half of all diagnoses attributable to variants in five genes: SLC26A4, MYO15A, MYO7A, CDH23, and PCDH15. As a reflection of the power of consanguinity mapping, 26 genes were identified as causative for NSHL in the Iranian population for the first time. In total, 179 deafness-causing variants were identified in 40 genes in 201 probands, including 110 novel single nucleotide or small insertion-deletion variants and 3 novel copy number variations. Several variants represent founder mutations. Conclusion This study attests to the power of TGE and massively parallel sequencing (TGE+MPS) as a diagnostic tool for the evaluation of hearing loss in Iran, and expands on our understanding of the genetics of HHL in this country. Families negative for variants in the genes represented on this panel represent an excellent cohort for novel gene discovery. PMID:26445815

  20. Consanguinity and the sib-pair method: An approach using identity by descent between and within individuals

    SciTech Connect

    Genin, E.; Clerget-Darpoux, F.

    1996-11-01

    To test for linkage between a trait and a marker, one can consider identical marker alleles in related individuals, for instance, sibs. For recessive diseases, it has been shown that some information may be gained from the identity by descent (IBD) of the two alleles of an affected inbred individual at the marker locus. The aim of this paper is to extend the sib-pair method of linkage analysis to the situation of sib pairs sampled from consanguineous populations. This extension takes maximum advantage of the information provided by both the IBD pattern between sibs and allelic identity within each sib of the pair. This is possible through the use of the condensed identity coefficients. Here, we propose a new test of linkage based on a {Chi}{sup 2}. We compare the performance of this test with that of the classical {Chi}{sup 2} test based on the distribution of sib pairs sharing 0, 1, or 2 alleles IBD. For sib pairs from first-cousin matings, the proposed test can better detect the role of a disease-susceptibility (DS) locus. Its power is shown to be greater than that of the classical test, especially for models where the DS allele may be common and incompletely penetrant; that is to say for situations that may be encountered in multifactorial diseases. A study of the impact of inbreeding on the expected proportions of sib pairs sharing 0, 1, or 2 alleles IBD is also performed here. Ignoring inbreeding, when in fact inbreeding exists, increases the rate of type I errors in tests of linkage. 21 refs., 8 figs., 9 tabs.

  1. Molecular characterisation of congenital glaucoma in a consanguineous Canadian community: a step towards preventing glaucoma related blindness.

    PubMed

    Martin, S N; Sutherland, J; Levin, A V; Klose, R; Priston, M; Héon, E

    2000-06-01

    Glaucoma is a leading cause of irreversible blindness in Canada. Congenital glaucoma usually manifests during the first years of life and is characterised by severe visual loss and autosomal recessive inheritance. Two disease loci, on chromosomes 1p36 and 2p21, have been associated with various forms of congenital glaucoma. A branch of a large six generation family from a consanguineous Amish community in south western Ontario was affected with congenital glaucoma and was studied by linkage and mutational analysis to identify the glaucoma related genetic defects. Linkage analysis using the MLINK component of the LINKAGE package (v 5.1) showed evidence of linkage to the 2p21 region (Zmax=3.34, theta=0, D2S1348 and D2S1346). Mutational analysis of the primary candidate gene, CYP1B1, was done by direct cycle sequencing, dideoxy fingerprinting analysis, and fragment analysis. Two different disease causing mutations in exon 3, 1410del13 and 1505G-->A, both segregated with the disease phenotype. The two different combinations of these alleles appeared to result in a variable expressivity of the phenotype. The compound heterozygote appeared to have a milder phenotype when compared to the homozygotes for the 13 bp deletion. The congenital glaucoma phenotype for this large inbred Amish family is the result of mutations in CYP1B1 (2p21). The molecular information derived from this study will be used to help identify carriers of the CYP1B1 mutation in this community and optimise the management of those at risk of developing glaucoma. PMID:10851252

  2. Impact of consanguinity on cardio-metabolic health and other diseases: findings from an Afro-Indian tribal community.

    PubMed

    Bhasin, Prerna; Kapoor, Satwanti

    2015-04-01

    Numerous anthropological reports have indicated consanguineous marriage in populous Asian countries, but the overall impact of first cousin marriage on survival and health of specific communities has rarely been reported. The aim of the study was to estimate risks for various complex diseases in the progeny of consanguineous parents. A cross-sectional study was conducted among 222 women among Siddis, a particularly vulnerable tribal group in the state of Gujarat, India, who are Sunni Muslims by faith. The Siddis are not part of the original Negrito element of India. They are descendants of Africans from Northeast and East Africa who were brought to India as slaves, soldiers, or servants. The degree of consanguinity between each female and her spouse and the degree of consanguinity between their parents and proband's grandparents were recorded with the help of pedigrees. The results showed that the rate of consanguinity in the present generation was 49 % (N = 109), higher than preceding generations. A significant association was observed between women's age, educational level, occupational status, consanguineous parents, and consanguinity. Socioeconomic status and consanguinity showed U-shaped associations. Nearly three times odds for cardio-metabolic risks (2.65 odds ratio (OR) for heart diseases, 2.44 OR for diabetes mellitus, and 2.62 OR for hypertension) have been contracted in the progeny of consanguineous marriage in the parental generation. The risk of cardio-metabolic diseases is higher in offspring of consanguineous couples, and there is a significant increase in the prevalence of common adult diseases.

  3. Discovery of four recessive developmental disorders using probabilistic genotype and phenotype matching among 4,125 families.

    PubMed

    Akawi, Nadia; McRae, Jeremy; Ansari, Morad; Balasubramanian, Meena; Blyth, Moira; Brady, Angela F; Clayton, Stephen; Cole, Trevor; Deshpande, Charu; Fitzgerald, Tomas W; Foulds, Nicola; Francis, Richard; Gabriel, George; Gerety, Sebastian S; Goodship, Judith; Hobson, Emma; Jones, Wendy D; Joss, Shelagh; King, Daniel; Klena, Nikolai; Kumar, Ajith; Lees, Melissa; Lelliott, Chris; Lord, Jenny; McMullan, Dominic; O'Regan, Mary; Osio, Deborah; Piombo, Virginia; Prigmore, Elena; Rajan, Diana; Rosser, Elisabeth; Sifrim, Alejandro; Smith, Audrey; Swaminathan, Ganesh J; Turnpenny, Peter; Whitworth, James; Wright, Caroline F; Firth, Helen V; Barrett, Jeffrey C; Lo, Cecilia W; FitzPatrick, David R; Hurles, Matthew E

    2015-11-01

    Discovery of most autosomal recessive disease-associated genes has involved analysis of large, often consanguineous multiplex families or small cohorts of unrelated individuals with a well-defined clinical condition. Discovery of new dominant causes of rare, genetically heterogeneous developmental disorders has been revolutionized by exome analysis of large cohorts of phenotypically diverse parent-offspring trios. Here we analyzed 4,125 families with diverse, rare and genetically heterogeneous developmental disorders and identified four new autosomal recessive disorders. These four disorders were identified by integrating Mendelian filtering (selecting probands with rare, biallelic and putatively damaging variants in the same gene) with statistical assessments of (i) the likelihood of sampling the observed genotypes from the general population and (ii) the phenotypic similarity of patients with recessive variants in the same candidate gene. This new paradigm promises to catalyze the discovery of novel recessive disorders, especially those with less consistent or nonspecific clinical presentations and those caused predominantly by compound heterozygous genotypes. PMID:26437029

  4. PACOM net assessment: Pakistani and Indian nuclear perceptions. Volume 1. Main report. Final report, 31 January-31 August 1983

    SciTech Connect

    Simon, J.

    1983-08-31

    This study evaluates the significance of nuclear proliferation as seen from the perspective of the Indian and Pakistani political-military leaderships, and speculates three hypothetical 1985 scenarios.

  5. Estimating the degree of identity by descent in consanguineous couples.

    PubMed

    Carr, Ian M; Markham, Sir Alexander F; Pena, Sérgio D J

    2011-12-01

    In some clinical and research settings, it is often necessary to identify the true level of "identity by descent" (IBD) between two individuals. However, as the individuals become more distantly related, it is increasingly difficult to accurately calculate this value. Consequently, we have developed a computer program that uses genome-wide SNP genotype data from related individuals to estimate the size and extent of IBD in their genomes. In addition, the software can compare a couple's IBD regions with either the autozygous regions of a relative affected by an autosomal recessive disease of unknown cause, or the IBD regions in the parents of the affected relative. It is then possible to calculate the probability of one of the couple's children suffering from the same disease. The software works by finding SNPs that exclude any possible IBD and then identifies regions that lack these SNPs, while exceeding a minimum size and number of SNPs. The accuracy of the algorithm was established by estimating the pairwise IBD between different members of a large pedigree with varying known coefficients of genetic relationship (CGR).

  6. Community perceptions of reasons for preference for consanguineous marriages in Pakistan.

    PubMed

    Hussain, R

    1999-10-01

    Although the recent Pakistan Demographic and Health Survey (DHS) show that two-thirds of marriages in Pakistan are consanguineous, the sociocultural determinants of such marriages remain largely unexplored. This paper examines the relative importance of the three commonly perceived reasons for such marriages: religious, economic and cultural. The analysis is based on qualitative data collected in 1995 from multi-ethnic and multi-religious communities in Karachi, the largest city of Pakistan. Results show that consanguineous marriages are preferred across all ethnic and religious groups to a varying degree, and that parents continue to be the prime decision-makers for marriages of both sons and daughters. The major reasons for a preference for consanguineous marriages are sociocultural rather than any perceived economic benefits, either in the form of consolidation of family property or smaller and less expensive dowries. Among Muslims, following religious traditions is the least commonly cited reason for such marriages. Despite the reported sociocultural advantages of consanguineous marriages, such unions are perceived to be exploitative as they perpetuate the existing power structures within the family. PMID:10581876

  7. The changing profile of consanguinity rates in Bahrain, 1990-2009.

    PubMed

    Al-Arrayed, Shaikha; Hamamy, Hanan

    2012-05-01

    Consanguineous marriage is traditional and respected in most communities of North Africa, the Middle East and West Asia, including Bahrain, with intra-familial unions accounting for 20-50+% of all marriages. Significant secular changes in consanguinity rates have been reported in recent decades in different populations. Among parents of 14,237 newborns in Bahrain in 2008-2009, the total consanguinity and first cousin marriage rates over a period of four months in 2008 were 10.9% and 6.9% respectively, while during all of 2009 the rates were 11.4% and 6.8% respectively. The study confirms that over a ten-year period first cousin marriage rates in Bahrain have declined from 24% to nearly 7%. Although advice against cousin marriages was not attempted at any stage in the comprehensive community genetics programmes in Bahrain, increasing the literacy of the public and of the health care providers on prevention strategies for genetic diseases could have contributed to this decline in consanguinity rate in Bahrain.

  8. The Effect of Consanguineous Marriage on Reading Disability in the Arab Community

    ERIC Educational Resources Information Center

    Abu-Rabia, Salim; Maroun, Lateefeh

    2005-01-01

    The present study examined the effect of consanguineous marriage in the Arab community on reading disabilities of offspring. It examined whether the rate of reading disabilities was higher among offspring of first-cousin parents than offspring of unrelated parents; and whether reading-disabled children of first-cousin parents were more disabled in…

  9. An analysis of consanguineous marriage in the Muslim population of India at regional and state levels.

    PubMed

    Bittles, A H; Hussain, R

    2000-01-01

    Consanguineous marriage is widely favoured in a large majority of the world's Islamic populations. According to recent estimates, the resident Muslim population of India is over 100 million. However, apart from a few numerically small or geographically defined surveys, little is known about their patterns of marriage preferences since partition of the Indian Subcontinent in 1947. This study seeks to determine the prevalence and patterns of consanguineous marriages contracted among Indian Muslims at regional and state levels during the last two generations. Data from the 1992/93 Indian National Family Health Survey (NFHS) were used in the analysis. The NFHS was a nationally-representative survey of ever-married women aged 13-49 years, conducted across 25 states of India. Of the initial 9845 respondents, 8436 were included in the final weighted analysis sample. Overall, 22.0% of marriages were found to be contracted between spouses related as second cousins or closer, ranging from 15.9% in the eastern states to 32.9% in the western states of India. In all parts of the country first cousin marriages were the preferred form of consanguineous union, and in four of the five regions paternal first cousin marriages predominated. Despite predictions to the contrary, there was no evidence of a significant change in the prevalence of consanguineous unions over the course of the study period, which extended from the late 1950s to the early 1990s.

  10. Prevalence of consanguineous marriages among shi'a populations of Lebanon.

    PubMed

    El-Kheshen, Ghadir; Saadat, Mostafa

    2013-09-01

    In genetics, a consanguineous marriage means union between couples who are related as second cousins or closer. The present cross-sectional study was carried out in order to illustrate the prevalence and types of consanguineous marriages in the Shi'a population living in widespread territories in Lebanon including the Bekaa Valley, the south of Lebanon and the southern suburb of Beirut. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 1203. Consanguineous marriage was classified by the degree of relationship between couples. The overall frequency of consanguinity was found to be 28.4%, with first cousin marriages (21.3%) being the most common type followed by first cousins once removed (5.5%), then double first cousins (0.8%). The frequencies of second cousin and beyond second cousin marriages were the same at 0.4% of all the marriages. The mean inbreeding coefficient (α) was estimated at about 0.0161 for the population. There were no significant differences between the three studied territories for frequencies of different types of marriages (p>0.1), nor were there significant differences between the rural and urban areas (p>0.1).

  11. An analysis of consanguineous marriage in the Muslim population of India at regional and state levels.

    PubMed

    Bittles, A H; Hussain, R

    2000-01-01

    Consanguineous marriage is widely favoured in a large majority of the world's Islamic populations. According to recent estimates, the resident Muslim population of India is over 100 million. However, apart from a few numerically small or geographically defined surveys, little is known about their patterns of marriage preferences since partition of the Indian Subcontinent in 1947. This study seeks to determine the prevalence and patterns of consanguineous marriages contracted among Indian Muslims at regional and state levels during the last two generations. Data from the 1992/93 Indian National Family Health Survey (NFHS) were used in the analysis. The NFHS was a nationally-representative survey of ever-married women aged 13-49 years, conducted across 25 states of India. Of the initial 9845 respondents, 8436 were included in the final weighted analysis sample. Overall, 22.0% of marriages were found to be contracted between spouses related as second cousins or closer, ranging from 15.9% in the eastern states to 32.9% in the western states of India. In all parts of the country first cousin marriages were the preferred form of consanguineous union, and in four of the five regions paternal first cousin marriages predominated. Despite predictions to the contrary, there was no evidence of a significant change in the prevalence of consanguineous unions over the course of the study period, which extended from the late 1950s to the early 1990s. PMID:10768421

  12. Phenotypes of Recessive Pediatric Cataract in a Cohort of Children with Identified Homozygous Gene Mutations (An American Ophthalmological Society Thesis)

    PubMed Central

    Khan, Arif O.; Aldahmesh, Mohammed A.; Alkuraya, Fowzan S.

    2015-01-01

    Purpose: To assess for phenotype-genotype correlations in families with recessive pediatric cataract and identified gene mutations. Methods: Retrospective review (2004 through 2013) of 26 Saudi Arabian apparently nonsyndromic pediatric cataract families referred to one of the authors (A.O.K.) and for which recessive gene mutations were identified. Results: Fifteen different homozygous recessive gene mutations were identified in the 26 consanguineous families; two genes and five families are novel to this study. Ten families had a founder CRYBB1 deletion (all with bilateral central pulverulent cataract), two had the same missense mutation in CRYAB (both with bilateral juvenile cataract with marked variable expressivity), and two had different mutations in FYCO1 (both with bilateral posterior capsular abnormality). The remaining 12 families each had mutations in 12 different genes (CRYAA, CRYBA1, AKR1E2, AGK, BFSP2, CYP27A1, CYP51A1, EPHA2, GCNT2, LONP1, RNLS, WDR87) with unique phenotypes noted for CYP27A1 (bilateral juvenile fleck with anterior and/or posterior capsular cataract and later cerebrotendinous xanthomatosis), EPHA2 (bilateral anterior persistent fetal vasculature), and BFSP2 (bilateral flecklike with cloudy cortex). Potential carrier signs were documented for several families. Conclusions: In this recessive pediatric cataract case series most identified genes are noncrystallin. Recessive pediatric cataract phenotypes are generally nonspecific, but some notable phenotypes are distinct and associated with specific gene mutations. Marked variable expressivity can occur from a recessive missense CRYAB mutation. Genetic analysis of apparently isolated pediatric cataract can sometimes uncover mutations in a syndromic gene. Some gene mutations seem to be associated with apparent heterozygous carrier signs. PMID:26622071

  13. Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency.

    PubMed

    Rivoisy, Claire; Gérard, Laurence; Boutboul, David; Malphettes, Marion; Fieschi, Claire; Durieu, Isabelle; Tron, François; Masseau, Agathe; Bordigoni, Pierre; Alric, Laurent; Haroche, Julien; Hoarau, Cyrille; Bérézné, Alice; Carmagnat, Maryvonnick; Mouillot, Gael; Oksenhendler, Eric

    2012-02-01

    The DEFI study has collected clinical data and biological specimens from kindreds with CVID. Patients with demonstrated parental consanguinity (cCVID group) were compared to patients without parental consanguinity (ncCVID). A total of 24 of the 436 patients with CVID had consanguineous parents. Age at first symptoms and age at diagnosis were comparable in the two groups. Some complications were more frequent in cCVID patients: splenomegaly (62.5% vs. 29%; p = 0.001), granulomatous disease (29% vs. 12%; p = 0.02), and bronchiectasis (58% vs. 29%; p = 0.003). A high incidence of opportunistic infections was also observed in this population (29% vs. 5%; p < 0.001). Distribution of B-cell subsets were similar in the two groups. Naïve CD4+ T cells were decreased in cCVID patients (15% vs. 28%; p < 0.001), while activated CD4 + CD95+ (88% vs. 74%; p = 0.002) and CD8 + HLA-DR + T cells (47% vs. 31%; p < 0.001) were increased in these patients when compared to ncCVID patients. Parental consanguinity is associated with an increased risk of developing severe clinical complications in patients with CVID. Most of these patients presented with severe T-cell abnormalities and should be considered with a diagnosis of late-onset combined immune deficiency (LOCID). Systematic investigation for parental consanguinity in patients with CVID provides useful information for specific clinical care and genetic screening. PMID:22002594

  14. Does gingival recession require surgical treatment?

    PubMed Central

    Chan, Hsun-Liang; Chun, Yong-Hee Patricia; MacEachern, Mark

    2016-01-01

    Gingival recession represents a clinical condition in adults frequently encountered in the general dental practice. It is estimated that 23% of adults in the US have one or more tooth surfaces with ≥ 3 mm gingival recession. Clinicians often time face dilemmas of whether or not to treat such a condition surgically. Therefore, we were charged by the editorial board to answer this critical question: “Does gingival recession require surgical treatment?” An initial condensed literature search was performed using a combination of gingival recession and surgery controlled terms and keywords. An analysis of the search results highlights our limited understanding of the factors that often guide the treatment of gingival recession. Understanding the etiology, prognosis and treatment of gingival recession continues to offer many unanswered questions and challenges in the field of periodontics as we strive to provide the best care possible for our patients. PMID:26427577

  15. Mutations in NSUN2 Cause Autosomal- Recessive Intellectual Disability

    PubMed Central

    Abbasi-Moheb, Lia; Mertel, Sara; Gonsior, Melanie; Nouri-Vahid, Leyla; Kahrizi, Kimia; Cirak, Sebahattin; Wieczorek, Dagmar; Motazacker, M. Mahdi; Esmaeeli-Nieh, Sahar; Cremer, Kirsten; Weißmann, Robert; Tzschach, Andreas; Garshasbi, Masoud; Abedini, Seyedeh S.; Najmabadi, Hossein; Ropers, H. Hilger; Sigrist, Stephan J.; Kuss, Andreas W.

    2012-01-01

    With a prevalence between 1 and 3%, hereditary forms of intellectual disability (ID) are among the most important problems in health care. Particularly, autosomal-recessive forms of the disorder have a very heterogeneous molecular basis, and genes with an increased number of disease-causing mutations are not common. Here, we report on three different mutations (two nonsense mutations, c.679C>T [p.Gln227∗] and c.1114C>T [p.Gln372∗], as well as one splicing mutation, g.6622224A>C [p.Ile179Argfs∗192]) that cause a loss of the tRNA-methyltransferase-encoding NSUN2 main transcript in homozygotes. We identified the mutations by sequencing exons and exon-intron boundaries within the genomic region where the linkage intervals of three independent consanguineous families of Iranian and Kurdish origin overlapped with the previously described MRT5 locus. In order to gain further evidence concerning the effect of a loss of NSUN2 on memory and learning, we constructed a Drosophila model by deleting the NSUN2 ortholog, CG6133, and investigated the mutants by using molecular and behavioral approaches. When the Drosophila melanogaster NSUN2 ortholog was deleted, severe short-term-memory (STM) deficits were observed; STM could be rescued by re-expression of the wild-type protein in the nervous system. The humans homozygous for NSUN2 mutations showed an overlapping phenotype consisting of moderate to severe ID and facial dysmorphism (which includes a long face, characteristic eyebrows, a long nose, and a small chin), suggesting that mutations in this gene might even induce a syndromic form of ID. Moreover, our observations from the Drosophila model point toward an evolutionarily conserved role of RNA methylation in normal cognitive development. PMID:22541559

  16. Consanguineous marriage in an urban area of Saudi Arabia: rates and adverse health effects on the offspring.

    PubMed

    al-Abdulkareem, A A; Ballal, S G

    1998-02-01

    The objective of this cross-sectional study was to determine the pattern and time trend of consanguineous marriage and its adverse health effects on the offspring in Dammam city, Eastern Province, in the Kingdom of Saudi Arabia. This city is known to attract Saudis from different parts of the country because it is in the heart of this industrial region. Five primary health care centers were randomly selected from different sectors of the city in addition to the city's only Maternity and Children's Hospital. For inclusion in the study a wife must have at least one pregnancy that terminated in either full term liveborn baby, still birth, or abortion. A total of 1307 ever-married Saudis completed a pre-structured questionnaire during an interview. The rate of consanguineous marriage was 52.0% with an average inbreeding coefficient of 0.0312. First-cousin marriages were the commonest (39.3%) of all matings. The consanguineous groups had a significantly higher number of pregnancies. The mean birth weight of the offspring of consanguineous couples was not statistically significant being less than that of the non-consanguineous. However, within the consanguineous groups the more closely related couples had smaller babies on average. No significant differences were noted for the rates of inherited diseases and reproductive wastage. The rate of consanguineous marriage in this city was high and so was the inbreeding coefficient. These figures place this nation among the countries with a high rate of consanguineous marriages. A nationwide study to determine accurately the relationship between consanguinity and inherited diseases has much to commend it.

  17. Streamflow Recession Analysis Incorporating Human Water Use

    NASA Astrophysics Data System (ADS)

    Thomas, B. F.; Vogel, R. M.

    2011-12-01

    Hydrologic studies of streamflow recessions are common in hydrology, yet nearly all previous studies have ignored the impact of human water withdrawals on the recession behavior of streamflow. The baseflow recession constant (Kb), commonly used in hydrologic models, can be estimated from a hydrologic recession. Resulting estimates of Kb are used widely in rainfall runoff models, low flow forecasting, and estimation of low flow characteristics. The accurate estimation of the baseflow recession constant is critical due to its common use in low flow characterization for water management strategies and Clean Water Act permitting requirements. This study documents the impact of water withdrawals on estimates of streamflow recession constants. We combine existing information on both groundwater and surface water resources and readily available information on human water use. We document that estimates of the baseflow recession constant depend critically upon the ratio of groundwater withdrawals to the average magnitude of baseflows. We document that without careful attention to the impact of groundwater withdrawals, estimates of streamflow recession constants will exhibit significant bias. Observed streamflow response is best approximated by a streamflow recession constant that incorporates human water use.

  18. Consanguineous Marital Union Resulting in a Progeny of Whistling-face Syndrome and Hemophilia: A Case Report.

    PubMed

    Gurjar, Vivek; Gurjar, Minal

    2015-04-01

    Many different types of genetic disorders are noted to be prevalent among consanguineous progeny. Although the most common type of consanguineous union in all major societies is between first cousins, the importance of customary influences is apparent from variations in the specific types of first-cousin marriages contracted. Epidemiological data for the prevalence of whistling-face syndrome (WFS) are not available, but less than a hundred cases reported in the literature are noted. We are presenting a case where a consanguineous marriage resulted in two of their children presenting with WFS and one with hemophilia.

  19. Consanguineous Marital Union Resulting in a Progeny of Whistling-face Syndrome and Hemophilia: A Case Report.

    PubMed

    Gurjar, Vivek; Gurjar, Minal

    2015-04-01

    Many different types of genetic disorders are noted to be prevalent among consanguineous progeny. Although the most common type of consanguineous union in all major societies is between first cousins, the importance of customary influences is apparent from variations in the specific types of first-cousin marriages contracted. Epidemiological data for the prevalence of whistling-face syndrome (WFS) are not available, but less than a hundred cases reported in the literature are noted. We are presenting a case where a consanguineous marriage resulted in two of their children presenting with WFS and one with hemophilia. PMID:25954077

  20. Rigid Basement and the Evolution of the Pakistani Convergent Margin

    NASA Astrophysics Data System (ADS)

    Haq, S. S.; Davis, D. M.

    2007-12-01

    In Pakistan, along the western edge of the Indian-Eurasian collision there are a series of fold-and-thrust belts that have highly variable strikes and shortening directions with respect to the local relative plate motion. Much of the complexity in the deformation of this margin can easily be explained by the shape, location, and long-term motion of a fragment of relatively rigid oceanic lithosphere that is believed to underlie the Katawaz Basin. In particular, the deformation that has formed the Sulaiman Range and Lobe is a direct consequence of the Katawaz Basin's over all higher strength. The presence of deformed sedimentary strata in the basin comparable to those presently found in the Indus delta are indicative of the basins long-term motion parallel to the Chaman fault zone. In Pakistan, the transition in the strike and shortening directions occurs over a short distance compared to the width of the fold-belts and the length of the margin. We present a series of analog models along with detailed quantitative analysis that we compare to the observed deformation as indicated by both geologic and geophysical data. By quantitatively distinguishing the style and magnitude of deformation in each of a variety of analog experiments we are able to evaluate the viability of various alternative models that have been proposed for fold- belt formation and evolution of the Pakistani margin, including our favored model. The model that best fits the geological and geophysical evidence suggests that the complexity of the Pakistani margin is a result of the long- term northeastward migration of the Katawaz basin along the curving trend of the Chaman fault zone. The vertically integrated mechanical strength of the Katawaz basin allows it to act as a strong 'backstop' that has relative motion to both stable India and stable Eurasia. This northeastward motion and the resulting clockwise rotation of the Katawaz 'block' during the margin's development can explain the location and

  1. HIV knowledge and risk behaviors among Pakistani and Afghani drug users in Quetta, Pakistan.

    PubMed

    Zafar, Tariq; Brahmbhatt, Heena; Imam, Ghazanfar; ul Hassan, Salman; Strathdee, Steffanie A

    2003-04-01

    Situated on the Pakistan-Afghan border, Quetta is home to growing numbers of Afghan refugees. We studied HIV knowledge and risk behaviors among Pakistani and Afghani drug users between July 2001 and November 2001. Of 959 drug users, all were male and the majority used heroin. Most were Pakistani (84.8%), 14.9% were Afghani, and 0.3% were Iranian. Relative to Pakistani drug users, a higher proportion of Afghanis reported no formal education, homelessness, and unemployment ( p <.001). Afghanis were more likely to have used an opiate as their first illicit drug (16% vs. 7%, p <.001), to have ever injected (18.8% vs. 12.3%, p =.04), to report needle sharing (72.2% vs. 48.2%, p =.08), or to report a drug user in their family ( p =.08). None of sexually active Afghanis had ever used a condom compared with 5.0% of the Pakistanis ( p =.01). Only 4.3% of Afghans had ever heard of HIV/AIDS compared with 18.3% of Pakistanis ( p <.001). Extremely low levels of HIV/AIDS awareness and high HIV risk behaviors were evident among drug users in Quetta, among whom Afghanis were especially vulnerable. Interventions to prevent transition to injection, needle exchange, and drug treatment are urgently required to prevent blood-borne infections. PMID:12640197

  2. Expanding the spectrum of PEX10-related peroxisomal biogenesis disorders: slowly progressive recessive ataxia.

    PubMed

    Renaud, Mathilde; Guissart, Claire; Mallaret, Martial; Ferdinandusse, Sacha; Cheillan, David; Drouot, Nathalie; Muller, Jean; Claustres, Mireille; Tranchant, Christine; Anheim, Mathieu; Koenig, Michel

    2016-08-01

    Peroxisomal biogenesis disorders (PBDs) consist of a heterogeneous group of autosomal recessive diseases, in which peroxisome assembly and proliferation are impaired leading to severe multisystem disease and early death. PBDs include Zellweger spectrum disorders (ZSDs) with a relatively mild clinical phenotype caused by PEX1, (MIM# 602136), PEX2 (MIM# 170993), PEX6 (MIM# 601498), PEX10 (MIM# 602859), PEX12 (MIM# 601758), and PEX16 (MIM# 603360) mutations. Three adult patients are reported belonging to a non-consanguineous French family affected with slowly progressive cerebellar ataxia, axonal neuropathy, and pyramidal signs. Mental retardation and diabetes mellitus were optional. The age at onset was in childhood or in adolescence (3-15 years). Brain MRI showed marked cerebellar atrophy. Biochemical blood analyses suggested a mild peroxisomal defect. With whole exome sequencing, two mutations in PEX10 were found in the three patients: c.827G>T (novel) causing the missense change p.Cys276Phe and c.932G>A causing the missense change p.Arg311Gln. The phenotypic spectrum related to PEX10 mutations includes slowly progressive, syndromic recessive ataxia.

  3. A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors

    SciTech Connect

    Brune, W.; Saul, M.; Becker, C.M.

    1996-05-01

    Dominant missense mutations in the human glycine receptor (GlyR) {alpha}1 subunit gene (GLRA1) give rise to hereditary hyperekplexia. These mutations impair agonist affinities and change conductance states of expressed mutant channels, resulting in a partial loss of function. In a recessive case of hyperekplexia, we found a deletion of exons 1-6 of the GLRA1 gene. Born to consanguineous parents, the affected child is homozygous for this GLRA1{sup null} allele consistent with a complete loss of gene function. The child displayed exaggerated startle responses and pronounced head-retraction jerks reflecting a disinhibition of vestigial brain-stem reflexes. In contrast, proprio- and exteroceptive inhibition of muscle activity previously correlated to glycinergic mechanisms were not affected. This case demonstrates that, in contrast to the lethal effect of a null allele in the recessive mouse mutant oscillator (Glra1{sup spd-ot}), the loss of the GlyR {alpha}1 subunit is effectively compensated in man. 38 refs.

  4. A recessive Nav1.4 mutation underlies congenital myasthenic syndrome with periodic paralysis

    PubMed Central

    Habbout, Karima; Poulin, Hugo; Rivier, François; Giuliano, Serena; Sternberg, Damien; Fontaine, Bertrand; Eymard, Bruno; Morales, Raul Juntas; Echenne, Bernard; King, Louise; Hanna, Michael G.; Männikkö, Roope; Chahine, Mohamed; Nicole, Sophie

    2016-01-01

    Objective: To determine the molecular basis of a complex phenotype of congenital muscle weakness observed in an isolated but consanguineous patient. Methods: The proband was evaluated clinically and neurophysiologically over a period of 15 years. Genetic testing of candidate genes was performed. Functional characterization of the candidate mutation was done in mammalian cell background using whole cell patch clamp technique. Results: The proband had fatigable muscle weakness characteristic of congenital myasthenic syndrome with acute and reversible attacks of most severe muscle weakness as observed in periodic paralysis. We identified a novel homozygous SCN4A mutation (p.R1454W) linked to this recessively inherited phenotype. The p.R1454W substitution induced an important enhancement of fast and slow inactivation, a slower recovery for these inactivated states, and a frequency-dependent regulation of Nav1.4 channels in the heterologous expression system. Conclusion: We identified a novel loss-of-function mutation of Nav1.4 that leads to a recessive phenotype combining clinical symptoms and signs of congenital myasthenic syndrome and periodic paralysis, probably by decreasing channel availability for muscle action potential genesis at the neuromuscular junction and propagation along the sarcolemma. PMID:26659129

  5. Pakistani and Bangladeshi Young Men: Re-Racialization, Class and Masculinity within the Neo-Liberal School

    ERIC Educational Resources Information Center

    Mac an Ghaill, Mairtin; Haywood, Chris

    2014-01-01

    This article explores Pakistani and Bangladeshi young men's experiences of schooling to examine what inclusion/exclusion means to them. Qualitative research was undertaken with 48 Pakistani and Bangladeshi young men living in areas of the West Midlands, England. The young men highlighted three key areas: the emergence of a schooling regime…

  6. Antinociceptive, antioxidant and phytochemical studies of Pakistani medicinal plants.

    PubMed

    Uddin, Ghias; Rauf, Abdur; Siddiqui, Bina Shaheen; Khan, Haroon; Barkatullah; Ullah, Rooh

    2016-05-01

    The aim of the current study was to evaluate the antinociceptive activity of the selected Pakistani medicinal plants (Chenopodium botrys, Micromeria biflora and Teucrium stocksianum) in-vivo followed by their antioxidant potential against 1,1-diphenyl-2-picrylhidrazyl (DPPH) in-vitro. The results demonstrated profound antinociceptive effect of both the crude methanolic extract of Chenopodium botrys (CBM) and subsequent aqueous fraction (CBW) of C. botrys with 80.76% and 84% pain relief in acetic acid induced writhing test at 100 mg/kg i.p respectively. Similarly the crude methanolic extract of Micromeria biflora (MBM) and its subsequent aqueous fraction (MBW) with 66.46% 78.08% pain reversal in acetic acid induced writhing test respectively at 100mg/kg i.p. However, the crude methanolic extract and isolated water fraction of Teucrium stocksianum (TS) did not show any significant effect at test doses. Both the crude extracts and aqueous fractions of selected medicinal plants exhibited marked scavenging effects on DPPH and therefore strongly support the antinociceptive activity. Phytochemical analysis indicated the presence of various classes of natural products (alkaloids, terpenoids, flavonoids etc.) and thus the current finding can be attributed to the presence of these compounds. In short, our findings provide a strong scientific background to the folk uses C. botrys and M. biflora in the management of various painful conditions. PMID:27166536

  7. Strategies for Supporting Recess in Elementary Schools

    ERIC Educational Resources Information Center

    Centers for Disease Control and Prevention, 2014

    2014-01-01

    Recess provides students with a needed break from their structured school day. It can improve children's physical, social, and emotional well-being, and enhance learning. Recess helps children meet the goal of 60 minutes of physical activity (PA) each day, as recommended by the US Department of Health and Human Services. National…

  8. The Crucial Role of Recess in Schools

    ERIC Educational Resources Information Center

    Ramstetter, Catherine L.; Murray, Robert; Garner, Andrew S.

    2010-01-01

    Background: Recess is at the heart of a vigorous debate over the role of schools in promoting optimal child development and well-being. Reallocating time to accentuate academic concerns is a growing trend and has put recess at risk. Conversely, pressure to increase activity in school has come from efforts to combat childhood obesity. The purpose…

  9. A Lebanese family with autosomal recessive oculo-auriculo-vertebral (OAV) spectrum and review of the literature: is OAV a genetically heterogeneous disorder?

    PubMed Central

    Farra, Chantal; Yunis, Khaled; Yazbeck, Nadine; Majdalani, Marianne; Charafeddine, Lama; Wakim, Rima; Awwad, Johnny

    2011-01-01

    Oculo-auriculo-vertebral (OAV) spectrum summarizes a continuum of ocular, auricular, and vertebral anomalies. Goldenhar syndrome is a variant of this spectrum and is characterized by pre-auricular skin tags, microtia, facial asymmetry, ocular abnormalities, and vertebral anomalies of different sizes and shapes. Most cases are thought to be sporadic. However, a few families were reported to have an autosomal recessive inheritance and other families’ presentation of the syndrome strongly supported an autosomal dominant inheritance. We report OAV in a female infant presenting with tracheomalacia, diaphragmatic hernia, encephalomeningocele, sacral neural tube defect, and cardiac defect and her brother having no more than dysmorphic features. The mode of inheritance in this family supports an autosomal recessive inheritance where the transmission was from normal first-degree consanguineous parents to one of the sons and to the daughter. This report further broadens the clinical presentation and symptoms of OAV and supports the hypothesis advancing OAV as a genetically heterogeneous disorder. PMID:23776370

  10. The crucial role of recess in school.

    PubMed

    Murray, Robert; Ramstetter, Catherine

    2013-01-01

    Recess is at the heart of a vigorous debate over the role of schools in promoting the optimal development of the whole child. A growing trend toward reallocating time in school to accentuate the more academic subjects has put this important facet of a child's school day at risk. Recess serves as a necessary break from the rigors of concentrated, academic challenges in the classroom. But equally important is the fact that safe and well-supervised recess offers cognitive, social, emotional, and physical benefits that may not be fully appreciated when a decision is made to diminish it. Recess is unique from, and a complement to, physical education--not a substitute for it. The American Academy of Pediatrics believes that recess is a crucial and necessary component of a child's development and, as such, it should not be withheld for punitive or academic reasons.

  11. Nutritional and radiological impact of dietary potassium on the Pakistani population.

    PubMed

    Akhter, P; Ashraf, N; Mohammad, D; Orfi, S D; Ahmad, N

    2003-04-01

    The nutritional status of dietary potassium and the radiological impact of its isotope (40)K were estimated for the Pakistani population. Potassium concentration was determined in dietary samples by atomic absorption spectrometry. An average potassium concentration was 4.54+/-0.89 mg/g, which leads to potassium dietary intake of 2.69+/-0.54 g/day and the radiological hazard due to (40)K activity was 79.94 Bq/day. The annual and lifetime effective doses calculated for the reference Pakistani man weighing 64 kg due to measured activity of (40)K were found to be 1.65 x 10(-4) Sv y(-1) and 8.27 x 10(-3) Sv, respectively. Measured data showed that the potassium concentration in the Pakistani diet is adequate and safe according to international standards.

  12. Consanguinity and other marriage market effects of a wealth shock in Bangladesh.

    PubMed

    Mobarak, Ahmed Mushfiq; Kuhn, Randall; Peters, Christina

    2013-10-01

    This paper uses a wealth shock from the construction of a flood protection embankment in rural Bangladesh coupled with data on the universe of all 52,000 marriage decisions between 1982 and 1996 to examine changes in marital prospects for households protected by the embankment relative to unprotected households living on the other side of the river. We use difference-in-difference specifications to document that brides from protected households commanded larger dowries, married wealthier households, and became less likely to marry biological relatives. Financial liquidity-constrained households appear to use within-family marriage (in which one can promise ex-post payments) as a form of credit to meet up-front dowry demands, but the resultant wealth shock for households protected by the embankment relaxed this need to marry consanguineously. Our results shed light on the socioeconomic roots of consanguinity, which carries health risks for offspring but can also carry substantial benefits for the families involved.

  13. Migration as a determinant of marriage pattern: preliminary report on consanguinity among Afghans.

    PubMed

    Wahab, Abdul; Ahmad, Mahmud; Akram Shah, Syed

    2006-05-01

    Two sample populations, one refugee and one resident, were studied. The frequencies of consanguineous marriages came out to be 49.8%and 55.4%, respectively, for the refugees and the residents. Caste endogamy was dominant both in the residents and the refugees. The mean coefficient of inbreeding was calculated to be 0.0303 for the refugee population and 0.0332 for the resident population samples. First cousin marriage was the dominant type of marriage in both samples; father's brother's daughter (FBD) marriage was more frequent among the refugees while mother's brother's daughter(MBD) marriage was more frequent among the residents. Education has no decreasing effect on the incidence of consanguineous marriages. A significant difference in the pattern of marriages in the refugees is observed after the Saur Revolution of 1979. PMID:16613618

  14. Practice of Consanguinity and Unusual Cases of Inherited Familial Chromosome Abnormalities: A Case Report

    PubMed Central

    Sanyal, Debarshi; Bhairi, Vidya; S Kadandale, Jayarama

    2016-01-01

    We present 2 cases of likely rare event. In case 1, 3rd degree consanguineous marriage revealed inv(6) with same break points in parents who were found to be phenotypically normal. The same inv(6) being inherited in progeny but presented with low AMH (anti Mullerian hormone) and high level of FSH (follicular stimulating hormone) leading to polycystic ovarian syndrome/premature ovarian failure. In case 2, a couple was presented with 2nd degree consanguineous marriage and referred for 2 recurrent/ missed abortions. The amounts of shared genes are suggestive of more lethal genetic outcomes and inferred endogamy is a major driver to reproductive fiascoes, the ancestries of which are deeply tied at the meiotic level. PMID:27386439

  15. Practice of Consanguinity and Unusual Cases of Inherited Familial Chromosome Abnormalities: A Case Report.

    PubMed

    Sanyal, Debarshi; Bhairi, Vidya; S Kadandale, Jayarama

    2016-01-01

    We present 2 cases of likely rare event. In case 1, 3(rd) degree consanguineous marriage revealed inv(6) with same break points in parents who were found to be phenotypically normal. The same inv(6) being inherited in progeny but presented with low AMH (anti Mullerian hormone) and high level of FSH (follicular stimulating hormone) leading to polycystic ovarian syndrome/premature ovarian failure. In case 2, a couple was presented with 2(nd) degree consanguineous marriage and referred for 2 recurrent/ missed abortions. The amounts of shared genes are suggestive of more lethal genetic outcomes and inferred endogamy is a major driver to reproductive fiascoes, the ancestries of which are deeply tied at the meiotic level. PMID:27386439

  16. Genome-Wide Linkage in a Highly Consanguineous Pedigree Reveals Two Novel Loci on Chromosome 7 for Non-Syndromic Familial Premature Ovarian Failure

    PubMed Central

    Caburet, Sandrine; Zavadakova, Petra; Ben-Neriah, Ziva; Bouhali, Kamal; Dipietromaria, Aurélie; Charon, Céline; Besse, Céline; Laissue, Paul; Chalifa-Caspi, Vered; Christin-Maitre, Sophie; Vaiman, Daniel; Levi, Giovanni; Veitia, Reiner A.; Fellous, Marc

    2012-01-01

    Background The human condition known as Premature Ovarian Failure (POF) is characterized by loss of ovarian function before the age of 40. A majority of POF cases are sporadic, but 10–15% are familial, suggesting a genetic origin of the disease. Although several causal mutations have been identified, the etiology of POF is still unknown for about 90% of the patients. Methodology/Principal Findings We report a genome-wide linkage and homozygosity analysis in one large consanguineous Middle-Eastern POF-affected family presenting an autosomal recessive pattern of inheritance. We identified two regions with a LODmax of 3.26 on chromosome 7p21.1-15.3 and 7q21.3-22.2, which are supported as candidate regions by homozygosity mapping. Sequencing of the coding exons and known regulatory sequences of three candidate genes (DLX5, DLX6 and DSS1) included within the largest region did not reveal any causal mutations. Conclusions/Significance We detect two novel POF-associated loci on human chromosome 7, opening the way to the identification of new genes involved in the control of ovarian development and function. PMID:22428046

  17. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity

    PubMed Central

    Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D.; Lawson, Jennifer A.; Airik, Rannar; Shril, Shirlee; Allen, Susan J.; Stein, Deborah; Al Kindy, Adila; Beck, Bodo B.; Cengiz, Nurcan; Moorani, Khemchand N.; Ozaltin, Fatih; Hashmi, Seema; Sayer, John A.; Bockenhauer, Detlef; Soliman, Neveen A.; Otto, Edgar A.; Lifton, Richard P.; Hildebrandt, Friedhelm

    2015-01-01

    Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering, and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis and allows identification of novel candidate genes. PMID:26489029

  18. Whole exome sequencing identifies causative mutations in the majority of consanguineous or familial cases with childhood-onset increased renal echogenicity.

    PubMed

    Braun, Daniela A; Schueler, Markus; Halbritter, Jan; Gee, Heon Yung; Porath, Jonathan D; Lawson, Jennifer A; Airik, Rannar; Shril, Shirlee; Allen, Susan J; Stein, Deborah; Al Kindy, Adila; Beck, Bodo B; Cengiz, Nurcan; Moorani, Khemchand N; Ozaltin, Fatih; Hashmi, Seema; Sayer, John A; Bockenhauer, Detlef; Soliman, Neveen A; Otto, Edgar A; Lifton, Richard P; Hildebrandt, Friedhelm

    2016-02-01

    Chronically increased echogenicity on renal ultrasound is a sensitive early finding of chronic kidney disease that can be detected before manifestation of other symptoms. Increased echogenicity, however, is not specific for a certain etiology of chronic kidney disease. Here, we performed whole exome sequencing in 79 consanguineous or familial cases of suspected nephronophthisis in order to determine the underlying molecular disease cause. In 50 cases, there was a causative mutation in a known monogenic disease gene. In 32 of these cases whole exome sequencing confirmed the diagnosis of a nephronophthisis-related ciliopathy. In 8 cases it revealed the diagnosis of a renal tubulopathy. The remaining 10 cases were identified as Alport syndrome (4), autosomal-recessive polycystic kidney disease (2), congenital anomalies of the kidney and urinary tract (3), and APECED syndrome (1). In 5 families, in whom mutations in known monogenic genes were excluded, we applied homozygosity mapping for variant filtering and identified 5 novel candidate genes (RBM48, FAM186B, PIAS1, INCENP, and RCOR1) for renal ciliopathies. Thus, whole exome sequencing allows the detection of the causative mutation in 2/3 of affected individuals, thereby presenting the etiologic diagnosis, and allows identification of novel candidate genes. PMID:26489029

  19. Effects of polygyny and consanguinity on high fertility in the rural Arab population in South Jordan.

    PubMed

    Sueyoshi, Shuji; Ohtsuka, Ryutaro

    2003-10-01

    Based on the authors' interview survey for 608 randomly selected women of the rural Arab population in the South Ghor district of Jordan, this paper examined the effects of polygyny and consanguinity on high fertility, which was recognized as natural fertility. The prevalence of polygynous and consanguineous marriages was 28.0% and 58.1%, respectively, largely reflecting the population's traditional marriage customs. The findings highlighted a significantly higher total marital fertility rate (TMFR) in the monogamous wives (10.5) than in the senior polygynous (8.1) and junior polygynous wives (8.6); the TMFR did not significantly differ among the wives of non-consanguineous, first-cousin and second-cousin marriages. The formation of polygynous marriage was decided by the husband, mostly as a result of his senior wife's infecundity or sub-fecundity, and the age of the husband at marriage to his junior polygynous wife was high in many cases, leading to a decline in this wife's fecundity.

  20. A new locus for autosomal recessive hereditary spastic paraplegia maps to chromosome 16q24.3.

    PubMed Central

    De Michele, G; De Fusco, M; Cavalcanti, F; Filla, A; Marconi, R; Volpe, G; Monticelli, A; Ballabio, A; Casari, G; Cocozza, S

    1998-01-01

    Hereditary spastic paraplegia is a genetically and phenotypically heterogeneous disorder. Both pure and complicated forms have been described, with autosomal dominant, autosomal recessive, and X-linked inheritance. Various loci (SPG1-SPG6) associated with this disorder have been mapped. Here, we report linkage analysis of a large consanguineous family affected with autosomal recessive spastic paraplegia with age at onset of 25-42 years. Linkage analysis of this family excluded all previously described spastic paraplegia loci. A genomewide linkage analysis showed evidence of linkage to chromosome 16q24.3, with markers D16S413 (maximum LOD score 3.37 at recombination fraction [theta] of .00) and D16S303 (maximum LOD score 3.74 at straight theta=.00). Multipoint analysis localized the disease gene in the most telomeric region, with a LOD score of 4.2. These data indicate the presence of a new locus linked to pure recessive spastic paraplegia, on chromosome 16q24.3, within a candidate region of 6 cM. PMID:9634528

  1. Rare Variants in the Notch Signaling Pathway Describe a Novel Type of Autosomal Recessive Klippel–Feil Syndrome

    PubMed Central

    Karaca, Ender; Yuregir, Ozge O.; Bozdogan, Sevcan T.; Aslan, Huseyin; Pehlivan, Davut; Jhangiani, Shalini N.; Akdemir, Zeynep C.; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M.; Erdin, Serkan; Muzny, Donna; Gibbs, Richard A.; Lupski, James R.

    2016-01-01

    Klippel–Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel–Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel–Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left–right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel–Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel’s deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel–Feil syndrome, and in addition—from a mechanistic standpoint—suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. PMID:26238661

  2. Autosomal-recessive SASH1 variants associated with a new genodermatosis with pigmentation defects, palmoplantar keratoderma and skin carcinoma

    PubMed Central

    Courcet, Jean- Benoît; Elalaoui, Siham Chafai; Duplomb, Laurence; Tajir, Mariam; Rivière, Jean-Baptiste; Thevenon, Julien; Gigot, Nadège; Marle, Nathalie; Aral, Bernard; Duffourd, Yannis; Sarasin, Alain; Naim, Valeria; Courcet-Degrolard, Emilie; Aubriot-Lorton, Marie- Hélène; Martin, Laurent; Abrid, Jamal Eddin; Thauvin, Christel; Sefiani, Abdelaziz; Vabres, Pierre; Faivre, Laurence

    2015-01-01

    SASH1 (SAM and SH3 domain-containing protein 1) is a tumor suppressor gene involved in the tumorigenesis of a spectrum of solid cancers. Heterozygous SASH1 variants are known to cause autosomal-dominant dyschromatosis. Homozygosity mapping and whole-exome sequencing were performed in a consanguineous Moroccan family with two affected siblings presenting an unclassified phenotype associating an abnormal pigmentation pattern (hypo- and hyperpigmented macules of the trunk and face and areas of reticular hypo- and hyperpigmentation of the extremities), alopecia, palmoplantar keratoderma, ungueal dystrophy and recurrent spinocellular carcinoma. We identified a homozygous variant in SASH1 (c.1849G>A; p.Glu617Lys) in both affected individuals. Wound-healing assay showed that the patient's fibroblasts were better able than control fibroblasts to migrate. Following the identification of SASH1 heterozygous variants in dyschromatosis, we used reverse phenotyping to show that autosomal-recessive variants of this gene could be responsible for an overlapping but more complex phenotype that affected skin appendages. SASH1 should be added to the list of genes responsible for autosomal-dominant and -recessive genodermatosis, with no phenotype in heterozygous patients in the recessive form, and to the list of genes responsible for a predisposition to skin cancer. PMID:25315659

  3. Rare variants in the notch signaling pathway describe a novel type of autosomal recessive Klippel-Feil syndrome.

    PubMed

    Karaca, Ender; Yuregir, Ozge O; Bozdogan, Sevcan T; Aslan, Huseyin; Pehlivan, Davut; Jhangiani, Shalini N; Akdemir, Zeynep C; Gambin, Tomasz; Bayram, Yavuz; Atik, Mehmed M; Erdin, Serkan; Muzny, Donna; Gibbs, Richard A; Lupski, James R

    2015-11-01

    Klippel-Feil syndrome is a rare disorder represented by a subgroup of segmentation defects of the vertebrae and characterized by fusion of the cervical vertebrae, low posterior hairline, and short neck with limited motion. Both autosomal dominant and recessive inheritance patterns were reported in families with Klippel-Feil. Mutated genes for both dominant (GDF6 and GDF3) and recessive (MEOX1) forms of Klippel-Feil syndrome have been shown to be involved in somite development via transcription regulation and signaling pathways. Heterotaxy arises from defects in proteins that function in the development of left-right asymmetry of the developing embryo. We describe a consanguineous family with a male proband who presents with classical Klippel-Feil syndrome together with heterotaxy (situs inversus totalis). The present patient also had Sprengel's deformity, deformity of the sternum, and a solitary kidney. Using exome sequencing, we identified a homozygous frameshift mutation (c.299delT; p.L100fs) in RIPPLY2, a gene shown to play a crucial role in somitogenesis and participate in the Notch signaling pathway via negatively regulating Tbx6. Our data confirm RIPPLY2 as a novel gene for autosomal recessive Klippel-Feil syndrome, and in addition-from a mechanistic standpoint-suggest the possibility that mutations in RIPPLY2 could also lead to heterotaxy. © 2015 Wiley Periodicals, Inc. PMID:26238661

  4. A novel frameshift mutation of DDHD1 in a Japanese patient with autosomal recessive spastic paraplegia.

    PubMed

    Miura, Shiroh; Morikawa, Takuya; Fujioka, Ryuta; Kosaka, Kengo; Yamada, Kohei; Hattori, Gohsuke; Motomura, Manabu; Taniwaki, Takayuki; Shibata, Hiroki

    2016-08-01

    Spastic paraplegia (SPG) type 28 is an autosomal recessive SPG caused by mutations in the DDHD1 gene. We examined a Japanese 54-years-old male patient with autosomal recessive SPG. His parents were consanguineous. He needed a wheelchair for transfer due to spastic paraplegia. There was a history of operations for bilateral hallux valgus, thoracic ossification of the yellow ligament, bilateral carpal tunnel syndrome, bilateral ankle contracture, and lumbar spinal canal stenosis. He noticed gait disturbance at age 14. He used a cane for walking in his 40s. On neurological examination, he showed hyperreflexia, spasticity, and weakness in the lower extremities and bilateral Babinski reflexes. Urinary dysfunctions and impaired vibration sense in the lower limbs were observed. By exome sequencing analysis using Agilent SureSelect and Illumina MiSeq, we identified 17,248 homozygous nucleotide variants in the patient. Through the examination of 48 candidate genes known to be responsible for autosomal recessive SPG, we identified a novel homozygous 4-bp deletion, c.914_917delGTAA, p.Ser305Ilefs*2 in exon2 of the DDHD1 gene encoding phosphatidic acid-preferring phospholipase A1 (PA-PLA1). The mutation is expected to cause a frameshift generating a premature stop codon 3-bp downstream from the deletion. In consequence, the DDHD domain that is known to be critical for PLA1 activity is completely depleted in the mutated DDHD1 protein, predicted to be a functionally null mutation of the DDHD1 gene. By Sanger sequencing, we confirmed that both parents are heterozygous for the mutation. This variation was not detected in 474 Japanese control subjects as well as the data of the 1,000G Project. We conclude that the novel mutation in DDHD1 is the causative variant for the SPG28 patient that is the first record of the disease in Japanese population. PMID:27216551

  5. Exome sequencing identifies recessive CDK5RAP2 variants in patients with isolated agenesis of corpus callosum.

    PubMed

    Jouan, Loubna; Ouled Amar Bencheikh, Bouchra; Daoud, Hussein; Dionne-Laporte, Alexandre; Dobrzeniecka, Sylvia; Spiegelman, Dan; Rochefort, Daniel; Hince, Pascale; Szuto, Anna; Lassonde, Maryse; Barbelanne, Marine; Tsang, William Y; Dion, Patrick A; Théoret, Hugo; Rouleau, Guy A

    2016-04-01

    Agenesis of the corpus callosum (ACC) is a common brain malformation which can be observed either as an isolated condition or as part of numerous congenital syndromes. Therefore, cognitive and neurological involvements in patients with ACC are variable, from mild linguistic and behavioral impairments to more severe neurological deficits. To date, the underlying genetic causes of isolated ACC remains elusive and causative genes have yet to be identified. We performed exome sequencing on three acallosal siblings from the same non-consanguineous family and identified compound heterozygous variants, p.[Gly94Arg];[Asn1232Ser], in the protein encoded by the CDK5RAP2 gene, also known as MCPH3, a gene previously reported to cause autosomal recessive primary microcephaly. Our findings suggest a novel role for this gene in the pathogenesis of isolated ACC. PMID:26197979

  6. Expanding the Clinical Spectrum of SPG11 Gene Mutations in Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum

    PubMed Central

    Aleem, Alice Abdel; Abu-Shahba, Nourhan; Swistun, Dominika; Silhavy, Jennifer; Bielas, Stephanie L.; Sattar, Shifteh; Gleeson, Joseph G.; Zaki, Maha

    2011-01-01

    Hereditary spastic paraplegia (HSP) represents a large group of neurological disorders characterized by progressive spasticity of the lower limbs. One subtype of HSP shows an autosomal recessive form of inheritance with this corpus callosum (ARHSP-TCC), and displays genetic heterogeneity with four known loci. We identified a consanguineous Egyptian family with five affected individuals with ARHSP-TCC. We found linkage to the SPG11 locus and identified a novel homozygous p.Q498X stop codon mutation in exon 7 in the SPG11 gene encoding Spatacsin. Cognitive impairment and polyneuropathy, reported as frequent in SPG11, were not evident. This family supports the importance of SPG11 as a frequent cause for ARHSP-TCC, and expands the clinic SPG11 spectrum. PMID:20971220

  7. Attitudes and first heterosexual experiences among Indians and Pakistanis in Britain: evidence from a national probability survey.

    PubMed

    Griffiths, C; Johnson, A M; Fenton, K A; Erens, B; Hart, G J; Wellings, K; Mercer, C H

    2011-03-01

    We compare attitudes, experiences of learning about sex and first intercourse among Indians (n = 393) and Pakistanis (n = 365) using a probability survey of Britain's general population aged 16-44 years conducted during 1999-2001 (n = 12,110). Higher proportions of Pakistanis (64.6%) and Indians (28.1%) reported religion as 'very important' versus 6.2% of other ethnicities. Pakistanis were more conservative in their attitudes, e.g. reporting premarital sex as wrong (adjusted odds ratios [AORs] for sociodemographic differences, 4.71 [men] and 6.59 [women]). Pakistanis were more likely to be married at first sex (AORs 6.2 [men] and 9.53 [women]), yet men were more likely than women to be in non-marital relationships at this time (69.4% versus 25.2%). Pakistani men and women and Indian women were more likely to report not using reliable contraception at first sex relative to others (AORs 2.33, 3.16 and 1.90, respectively). Pakistani and Indian women were more likely than others to report school lessons as their main source of sex education (AORs 2.23 and 1.77) and not discussing sex with their parents during adolescence (AORs 2.04 and 2.62). These unique data have implications for ensuring that sex and relationship education and health promotion messages are appropriately planned, targeted and delivered to benefit Pakistanis and Indians. PMID:21464449

  8. Genetics Home Reference: autosomal recessive hypotrichosis

    MedlinePlus

    ... erythema), itchiness (pruritus), or missing patches of skin (erosions) on the scalp. In areas of poor hair ... recessive hypotrichosis with monilethrix hairs and congenital scalp erosions. J Invest Dermatol. 2006 Jun;126(6):1286- ...

  9. Systematic review of suicide in economic recession

    PubMed Central

    Oyesanya, Mayowa; Lopez-Morinigo, Javier; Dutta, Rina

    2015-01-01

    AIM: To provide a systematic update of the evidence concerning the relationship between economic recession and suicide. METHODS: A keyword search of Ovid Medline, Embase, Embase Classic, PsycINFO and PsycARTICLES was performed to identify studies that had investigated the association between economic recession and suicide. RESULTS: Thirty-eight studies met predetermined selection criteria and 31 of them found a positive association between economic recession and increased suicide rates. Two studies reported a negative association, two articles failed to find such an association, and three studies were inconclusive. CONCLUSION: Economic recession periods appear to increase overall suicide rates, although further research is warranted in this area, particularly in low income countries. PMID:26110126

  10. Have Employment Patterns in Recessions Changed?.

    ERIC Educational Resources Information Center

    Bowers, Norman

    1981-01-01

    A survey of postwar recessions shows that the increasing proportion of service sector jobs has moderated overall employment declines and that women in nontraditional jobs, Blacks, and youths bear a disproportionate share of job losses. (LRA)

  11. Drug Issues Affecting Chinese, Indian and Pakistani People Living in Greater Glasgow

    ERIC Educational Resources Information Center

    Ross, A. J.; Heim, D.; Bakshi, N.; Davies, J. B.; Flatley, K. J.; Hunter, S. C.

    2004-01-01

    This paper describes research on drug issues affecting Chinese, Indian and Pakistani people living in Greater Glasgow. There were two strands: (i) a questionnaire-based survey of young people and focus groups; (ii) interviews with young people and adults. The primary aims were to gather prevalence data and to investigate perceptions about current…

  12. Pakistani Teachers' Perceptions of Kindergarten Children's Learning: An Exploration of Understanding and Practice

    ERIC Educational Resources Information Center

    Pardhan, Almina

    2012-01-01

    This paper considers perceptions of children's learning and classroom practice to support learning in the Pakistani early years educational context. In Pakistan, there is a growing focus on quality provision of early childhood education and building early childhood education teacher capacity. Over the course of one academic year, data were…

  13. Comparative Study of Suicide Potential among Pakistani and American Psychiatric Patients

    ERIC Educational Resources Information Center

    Farooqi, Yasmin Nilofer

    2004-01-01

    This study compared suicide potential and suicide attempts in 50 Pakistani and 50 American psychiatric patients all of whom reported a positive history of suicide attempts during the past 1-5 years. It further explored the role of nationality, gender, diagnosis, and marital status in respondents' potential for suicide and suicide attempts. The…

  14. Young Pakistani Muslim Women's Reflections on Difference, Future, and Family

    ERIC Educational Resources Information Center

    Zaidi, Sara M.

    2012-01-01

    This dissertation employs data collected from multiple sites in Southern California over a period of nine months. Several in-depth ethnographic interviews and participant observations were conducted with Pakistani Muslim women (age 17-22) and their parents in an effort to better understand the influence that parents and ethno-religious communities…

  15. Attitudes of Pakistani Community Members and Staff toward People with Intellectual Disability

    ERIC Educational Resources Information Center

    Patka, Mazna; Keys, Christopher B.; Henry, David B.; McDonald, Katherine E.

    2013-01-01

    The acceptance and inclusion of persons with intellectual disability can vary across cultures, and understanding attitudes can provide insight into such variation. To our knowledge, no previous study has explored attitudes toward people with intellectual disability among Pakistani community members and disability service providers. We administered…

  16. Relation of Home Chaos to Cognitive Performance and Behavioral Adjustment of Pakistani Primary School Children

    ERIC Educational Resources Information Center

    Shamama-tus-Sabah, Syeda; Gilani, Nighat; Wachs, Theodore D.

    2011-01-01

    Recent findings from Western developed countries have linked home chaos to children's cognitive performance and behavioral problems. In the present paper we test whether the same pattern of associations can be replicated in a non-Western developing country. Our sample was 203 Pakistani primary school children. To assess home chaos the Confusion,…

  17. Continuing Bonds in Bereaved Pakistani Muslims: Effects of Culture and Religion

    ERIC Educational Resources Information Center

    Suhail, Kausar; Jamil, Naila; Oyebode, Jan; Ajmal, Mohammad Asir

    2011-01-01

    This study explores the bereavement process and continuing bond in Pakistani Muslims with the focus on how culture and religion influence these processes. Ten participants were interviewed and their transcribed interviews were analyzed using a grounded theory approach. Three main domains were identified from the narratives expressed by the…

  18. Role of ICT in Shaping the Future of Pakistani Higher Education System

    ERIC Educational Resources Information Center

    Shaikh, Zaffar Ahmed; Khoja, Shakeel Ahmed

    2011-01-01

    This study examined the challenges faced by the Pakistani higher education system (HES) in integrating information and communication technology (ICT); it aimed at understanding ICT needs, measuring the increase in ICT demand, determining the relationship between ICT and HES performance, and understanding how the HES copes with the challenges of…

  19. PACOM net assessment: Pakistani and Indian nuclear perceptions. Volume 2. Appendix. Sanitized. Technical report

    SciTech Connect

    Yim, S.

    1983-08-31

    The conclusions of a number of the commentators in the documents from which this information was derived are that the Pakistani and Indian nuclear weapons programs are stimulated by their rivalry and fueled by the weapons aid and aid to nuclear-power programs supplied to each country by the U.S. and the USSR.

  20. Willingness to Communicate in English as a Second Language: A Case Study of Pakistani Undergraduates

    ERIC Educational Resources Information Center

    Bukhari, Syeda Farzana; Cheng, Xiaoguang; Khan, Salman Ali

    2015-01-01

    Willingness to communicate (WTC) construct plays an important role in second language (L2) teaching and learning. Almost any second language learner is likely to respond to a direct question, but many will not continue or initiate communication. The present study investigates Pakistani undergraduate students' perception of their willingness to…

  1. Obesity and Minority--Changing Meanings of Big Bodies among Young Pakistani Obesity Patients in Norway

    ERIC Educational Resources Information Center

    Wathne, Kjetil; Mburu, Christina Brux; Middelthon, Anne-Lise

    2015-01-01

    Globally, paediatric obesity causes widespread concern, and the role of ethnicity is an important focus. Investigating how culture can mediate health-related behaviour through ideas about bodies, food and physical activity, while addressing a notion that the Pakistani community in Norway is particularly conservative and slow to change, this…

  2. Pakistani Government Secondary Schools Students' Attitudes towards Communicative Language Teaching and Grammar Translation in Quetta, Balochistan

    ERIC Educational Resources Information Center

    Muhammad, Zeeshan

    2016-01-01

    Students' attitudes towards an English language teaching approach play an important role for its implementation success or failure. This study measured Pakistani government school students' attitudes towards Communicative Language Teaching (CLT) and Grammar Translation (GT). A survey instrument was used to assess students' attitudes. Data were…

  3. HYDRORECESSION: A toolbox for streamflow recession analysis

    NASA Astrophysics Data System (ADS)

    Arciniega, S.

    2015-12-01

    Streamflow recession curves are hydrological signatures allowing to study the relationship between groundwater storage and baseflow and/or low flows at the catchment scale. Recent studies have showed that streamflow recession analysis can be quite sensitive to the combination of different models, extraction techniques and parameter estimation methods. In order to better characterize streamflow recession curves, new methodologies combining multiple approaches have been recommended. The HYDRORECESSION toolbox, presented here, is a Matlab graphical user interface developed to analyse streamflow recession time series with the support of different tools allowing to parameterize linear and nonlinear storage-outflow relationships through four of the most useful recession models (Maillet, Boussinesq, Coutagne and Wittenberg). The toolbox includes four parameter-fitting techniques (linear regression, lower envelope, data binning and mean squared error) and three different methods to extract hydrograph recessions segments (Vogel, Brutsaert and Aksoy). In addition, the toolbox has a module that separates the baseflow component from the observed hydrograph using the inverse reservoir algorithm. Potential applications provided by HYDRORECESSION include model parameter analysis, hydrological regionalization and classification, baseflow index estimates, catchment-scale recharge and low-flows modelling, among others. HYDRORECESSION is freely available for non-commercial and academic purposes.

  4. Exclusion of the locus for autosomal recessive pseudohypoaldosteronism type 1 from the mineralocorticoid receptor gene region on human chromosome 4q by linkage analysis

    SciTech Connect

    Chung, E.; Hanukoglu, A.; Rees, M.; Thompson, R.; Gardiner, R.M.

    1995-10-01

    Pseudohypoaldosteronism type 1 (PHA1) is an uncommon inherited disorder characterized by salt-wasting in infancy arising from target organ unresponsiveness to mineralocorticoids. Clinical expression of the disease varies from severely affected infants who may die to apparently asymptomatic individuals. Inheritance is Mendelian and may be either autosomal dominant or autosomal recessive. A defect in the mineralocortiocoid receptor has been implicated as a likely cause of PHA1. The gene for human mineralocorticoid receptor (MLR) has been cloned and physically mapped to human chromosome 4q31.1-31.2. The etiological role of MLR in autosomal recessive PHA1 was investigated by performing linkage analysis between PHA1 and three simple sequence length polymorphisms (D4S192, D4S1548, and D4S413) on chromosome 4q in 10 consanguineous families. Linkage analysis was carried out assuming autosomal recessive inheritance with full penetrance and zero phenocopy rate using the MLINK program for two-point analysis and the HOMOZ program for multipoint analysis. Lod scores of less than -2 were obtained over the whole region from D4S192 to D4S413 encompassing MLR. This provides evidence against MLR as the site of mutations causing PHA1 in the majority of autosomal recessive families. 34 refs., 3 figs., 2 tabs.

  5. An intronic deletion in the PROM1 gene leads to autosomal recessive cone-rod dystrophy

    PubMed Central

    Eidinger, Osnat; Leibu, Rina; Newman, Hadas; Rizel, Leah; Perlman, Ido

    2015-01-01

    Purpose To investigate the genetic basis for autosomal recessive cone-rod dystrophy (CRD) in a consanguineous Israeli Jewish family. Methods Patients underwent a detailed ophthalmic evaluation, including eye examination, visual field testing, optical coherence tomography (OCT), and electrophysiological tests, electroretinography (ERG) and visual evoked potential (VEP). Genome-wide homozygosity mapping using a single nucleotide polymorphism (SNP) array was performed to identify homozygous regions shared among two of the affected individuals. Mutation screening of the underlying gene was performed with direct sequencing. In silico and in vitro analyses were used to predict the effect of the identified mutation on splicing. Results The affected family members are three siblings who have various degrees of progressive visual deterioration, glare, color vision abnormalities, and night vision difficulties. Visual field tests revealed central scotomas of different extension. Cone and rod ERG responses were reduced, with cones more severely affected. Homozygosity mapping revealed several homozygous intervals shared among two of the affected individuals. One included the PROM1 gene. Sequence analysis of the 26 coding exons of PROM1 in one affected individual revealed no mutations in the coding sequence or in intronic splice sites. However, in intron 21, proximate to the intron–exon junction, we observed a homozygous 10 bp deletion between positions −26 and −17 (c.2281–26_-17del). The deletion was linked to a known SNP, c.2281–6C>G. The deletion cosegregated with the disease in the family, and was not detected in public databases or in 101 ethnically-matched control individuals. In silico analysis predicted that this deletion would lead to altered intron 21 splicing. Bioinformatic analysis predicted that a recognition site for the SRSF2 splicing factor is located within the deleted sequence. The in vitro splicing assay demonstrated that c.2281–26_-17del leads to

  6. She stands alone: Pakistani woman film director, Shireen Pasha.

    PubMed

    Mustafa, A

    1995-01-01

    This article describes the activities of film director Shireen Pasha in promoting truth in the mass media in Pakistan. Pasha is described as one who finds it inexcusable in a state-subsidized system that national problems of poverty are not aired openly. Pasha has pursued the goal of exposing the real lives of Pakistanis on film in contrast to the publicly aired segments of "pretty girls in nice drawing rooms." Foreign channels available through satellite communications technology are viewed by Pasha as inappropriate with regard to people's needs and uncreative. Pakistan began with one channel, PTV, which recently refused to air her documentary on living conditions in Pakistan's rural areas "The Travelogue Pakistan." "The Walled City of Lahore" was her film about life in the old city. Both films poetically depicted the honor of humans and their struggle to stay alive. Some of her documentaries are made to show the value of indigenous skills, centuries old know-how, and traditions, regardless of the poverty. Pasha is described as fighting with PTV management over use of resources. Pasha desires to invest in training people to do documentaries or be more field-oriented rather than investing in equipment. Pasha joined PTV in 1975 and left in 1990. Pasha is recognized for her isolation as a woman in the business world, her commitment to exposing remote cultures and truth, and the odds she must confront in attaining her goals. Pasha is committed to doing extensive research, usually conducted during the summer months, in order to construct a credible story line that is produced usually during the winter months. One model of film story line is defined as one where women are portrayed as starting from an indigenous skill or knowledge and shifting to a greater position of power and control over their lives. Pasha believes that people who make films have the responsibility to evoke a reaction in people and to offer solutions. Two acclaimed films, which were supported by

  7. The fate of 12 recessive mutations in a single village.

    PubMed

    Zlotogora, J; Hujerat, Y; Barges, S; Shalev, S A; Chakravarti, A

    2007-03-01

    In a Muslim Arab village, relatively isolated because of the preference of consanguineous marriages, we studied the fate of 12 mutations in 5 different genes. The study was based on carriers detected among relatives of affected patients and of carriers discovered in a random sample of 424 adults. Most of the mutations have been introduced by a carrier(s) originating from another village, but a few have been de novo events. Mutations that are very frequent in the entire village were introduced soon after the foundation of the village. Examples of such mutations are [GBJ2, 35Gdel] and [MEFV, M680I], with a carrier frequency of 7.8% and 6.2%, respectively. Many of the other mutations that are rare were introduced recently into the village and are frequent only among the descendants of the first couple carrying the mutation. For instance all the carriers of [ARSA, Q190H], responsible for metachromatic leukodystrophy, were found among the 218 descendants of a couple who were living in the village 4 generations ago. Since the village is typical for the region this study allows for some general conclusions to be drawn. In a population with a high degree of inbreeding the diagnosis of a single family with a patient(s) affected with a recessive disorder points to a recent event, while the finding of a rare disease in several families from an inbred population points to an older mutation. Mutations are often "exported" from one population to another by marriage. In the new inbred population this novel mutation will either be lost or will become frequent as the result of a founder effect. These observations are important for genetic counselling in the case of a recent mutation, since only the descendants of the founder couple are at risk, while in the case of older mutations the risk may be for the entire village. In the case of those frequent ancient mutations, the risk for a relative of an affected individual will be similar whether he marries a close relative or any random

  8. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations.

  9. Genetic Counseling and Screening of Consanguineous Couples and Their Offspring: Recommendations of the National Society of Genetic Counselors.

    PubMed

    Bennett, Robin L; Motulsky, Arno G; Bittles, Alan; Hudgins, Louanne; Uhrich, Stefanie; Doyle, Debra Lochner; Silvey, Kerry; Scott, C Ronald; Cheng, Edith; McGillivray, Barbara; Steiner, Robert D; Olson, Debra

    2002-04-01

    The objective of this document is to provide recommendations for genetic counseling and screening for consanguineous couples (related as second cousins or closer) and their offspring with the goals of1. providing preconception reproductive options2. improving pregnancy outcome and identifying reproductive choices3. reducing morbidity and mortality in the 1st years of life, and4. respecting psychosocial and multicultural issues.The recommendations are the opinions of a multicenter working group (the Consanguinity Working Group (CWG)) with expertise in genetic counseling, medical genetics, biochemical genetics, genetic epidemiology, pediatrics, perinatology, and public health genetics, which was convened by the National Society of Genetic Counselors (NSGC). The consensus of the CWG and NSGC reviewers is that beyond a thorough medical family history with follow-up of significant findings, no additional preconception screening is recommended for consanguineous couples. Consanguineous couples should be offered similar genetic screening as suggested for any couple of their ethnic group. During pregnancy, consanguineous couples should be offered maternal-fetal serum marker screening and high-resolution fetal ultrasonography. Newborns should be screened for impaired hearing and detection of treatable inborn errors of metabolism. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. The professional judgment of a health care provider, familiar with the facts and circumstances of a specific case, will always supersede these recommendations. PMID:26141656

  10. Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation

    PubMed Central

    Gregory, L. C.; Humayun, K. N.; Turton, J. P. G.; McCabe, M. J.; Rhodes, S. J.

    2015-01-01

    Background: LHX4 encodes a member of the LIM-homeodomain family of transcription factors that is required for normal development of the pituitary gland. To date, only incompletely penetrant heterozygous mutations in LHX4 have been described in patients with variable combined pituitary hormone deficiencies. Objective/Hypothesis: To report a unique family with a novel recessive variant in LHX4 associated with a lethal form of congenital hypopituitarism that was identified through screening a total of 97 patients. Method: We screened 97 unrelated patients with combined pituitary hormone deficiency, including 65% with an ectopic posterior pituitary, for variants in the LHX4 gene using Sanger sequencing. Control databases (1000 Genomes, dbSNP, Exome Variant Server, ExAC Browser) were consulted upon identification of variants. Results: We identified the first novel homozygous missense variant (c.377C>T, p.T126M) in two deceased male patients of Pakistani origin with severe panhypopituitarism associated with anterior pituitary aplasia and posterior pituitary ectopia. Both were born small for gestational age with a small phallus, undescended testes, and mid-facial hypoplasia. The parents' first-born child was a female with mid-facial hypoplasia (DNA was unavailable). Despite rapid commencement of hydrocortisone and T4 in the brothers, all three children died within the first week of life. The LHX4(p.T126M) variant is located within the LIM2 domain, in a highly conserved location. The absence of homozygosity for the variant in over 65 000 controls suggests that it is likely to be responsible for the phenotype. Conclusion: We report, for the first time to our knowledge, a novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life. PMID:25871839

  11. Aeroacoustical Study of the Tgv Pantograph Recess

    NASA Astrophysics Data System (ADS)

    NOGER, C.; PATRAT, J. C.; PEUBE, J.; PEUBE, J. L.

    2000-03-01

    The general focus of this aerodynamic noise research, induced by turbulent incompressible flow, is to improve our knowledge of acoustic production mechanisms in the TGV pantograph recess in order to be able to reduce the radiated noise. This work is performed under contract with SNCF as a part of the German-French Cooperation DEUFRAKO K2, and is supported by French Ministries for Transport and Research. Previous studies on TGV noise source locations (DEUFRAKO K) have identified the pantograph recess as one of the important aerodynamic noise sources, for speeds higher than 300 km/h, due to flow separation. The pantograph recess is a very complex rectangular cavity, located both on the power car and the first coach roofs of the TGV, and has not been studied before due to the complex shapes. Its aeroacoustic features are investigated experimentally in a low-subsonic wind tunnel, on a realistic 1/7th scale mock-up both with and without pantographs. Flow velocities, estimated with hot-wire anemometry, and parietal visualizations show the flow to reattach on the recess bottom wall and to separate again at the downstream face. Wall pressure fluctuations and “acoustic” measurements using 14 and 12 in microphones respectively are also measured to qualify the flow: no aerodynamic or acoustic oscillations are observed. The study indicates that the pantograph recess has a different behaviour compared to the usual cavity grazing flows.

  12. Management and prevention of gingival recession.

    PubMed

    Merijohn, George K

    2016-06-01

    Gingival recession is highly prevalent worldwide. It increases the risk for root caries and can interfere with patient comfort, function and esthetics. Progressive gingival recession also increases the risk of tooth loss secondary to clinical attachment loss. Although mitigating the causes of gingival recession decreases its incidence and severity, implementing practical management and prevention strategies in the clinical setting can be challenging. Identification of susceptible patients and evaluating them for the presence of modifiable risk exposures are essential first steps in developing action plans for appropriate interventions. This article reviews these steps and introduces chairside tools that can help in the selection of interventions designed to reduce the risk of future gingival recession and may also facilitate patient communication. Practical decision-making criteria are proposed for when and how to monitor gingival recession, for deciding when a patient is a candidate for surgical evaluation or referral to a periodontist, and, if surgery is the treatment of choice, what should be considered as key surgical outcome objectives. PMID:27045439

  13. Access to Power: Governance and Development in the Pakistani Electrical Power Sector

    NASA Astrophysics Data System (ADS)

    Naqvi, Ijlal

    This dissertation explores governance in Pakistan through a study of the state-run electrical power sector. At both the micro and macro level, the Pakistani power sector provides a lens into the heart of the Pakistani state and its governance institutions. This ethnographic and historical study offers an in-depth look at state operations in a developing country, situates the current Pakistani power crisis in a larger context of continuity through periods of dictatorship and democracy, and suggests how efforts to make state service delivery more responsive to citizens might be reconceived. A historical review of the Pakistani power sector establishes first and foremost that the current crisis is the product of longer-term processes for which the policy solutions currently being proposed (with the support of international donors and multilateral lenders) are inadequate. Depoliticized attempts at power sector reform have little to offer in light of the pervasively informal and negotiated nature of the fragmented Pakistani state. The institutions of power sector governance are mutually constituted by the formal rules and the informal---personal relationships, language, violence, money, and power. These rules of the game are as relevant to relations within and between public sector organizations as they are to the engagement of citizens with their state. The same rules apply at the margins of the state---informal squatter settlements---as at the core, though the resources brought to bear and the resultant outcomes are different. The internal incoherence of this state underscores the limitations of formal rules in determining outcomes, and the poor prospects for reform efforts that focus exclusively on the formal aspects of governance. To proactively engage with the question of political will leads away from top-down policy perspectives and counter to the depoliticizing tendencies that currently shape policy reforms. Instead, an energized and informed local participation

  14. Consanguinity and early mortality in the Muslim populations of India and Pakistan.

    PubMed

    Hussain, R; Bittles, A H; Sullivan, S

    2001-01-01

    Empirical information from studies conducted in Pakistan has indicated a high level of offspring mortality that can be attributed to parental consanguinity even when non-biological variables are controlled. However, with the exception of some small and geographically restricted studies, few comparable data are available on the influence of inbreeding in child survival among the Muslim population of India, which numbers between 100 and 120 million. The present study compares deaths during the first 5 years of life among the offspring of first cousin (F = 0.0625) and non-consanguineous unions (F = 0), using data collected in the 1992-1993 Indian National Family Health Survey (NFHS) and the 1990-1991 Pakistan Demographic and Health Survey (PDHS). The focus was on determinants of mortality in live-born children to age 5 years. In both countries, bivariate analyses indicated that mortality was significantly increased in the offspring of first cousin unions during the neonatal and post-neonatal, total infant, and under-5 year periods. The findings were confirmed by multivariate regression, which incorporated control for a range of biological and demographic factors.

  15. "Universal" Recession Curves and their Geomorphological Roots

    NASA Astrophysics Data System (ADS)

    Marani, M.; Biswal, B.

    2011-12-01

    The basic structural organization of channel networks, and of the connected hillslopes, have been shown to be intimately linked to basin responses to rainfall events, leading to geomorphological theories of the hydrologic response. Here, We identify a previously undetected link between the river network morphology and key recession curves properties. We show that the power-law exponent of -dQ/dt vs. Q curves is related to the power-law exponent of N(l) vs. G(l) curves (which we show to be connected to Hack's law), where l is the downstream distance from the channel heads, N(l) is the number of channel reaches exactly located at a distance l from their channel head, and G(l) is the total length of the network located at a distance greater or equal to l from channel heads. We then generalize the power-law expressions of recession curves, to identify "universal" curves, independent of the initial moisture conditions and of basin area, by making the -dQ/dt vs. Q curve non-dimensional using an index discharge representative of initial moisture conditions. We subsequently rescale the geomorphic recession curve, N(l) vs. G(l), producing a collapse of the geomorphic recession curves constructed from the DTM's of 67 US study basins. Finally, by use of the specific discharge u = Q/A, we link the two previous results and define the specific recession curves, whose collapse across basins within homogeneous geographical areas lends further, decisive, support to the notion that the statistical properties of observational recession curves bear the signature of the geomorphological structure of the networks producing them.

  16. Missense mutation (E150K) of rhodopsin in autosomal recessive retinitis pigmentosa

    SciTech Connect

    Orth, U.; Oehlmann, R.; Gal, A.

    1994-09-01

    Missense or nonsense mutations of the rhodopsin gene have been implied in the pathogenesis of at least 3 different traits; autosomal dominant retinitis pigmentosa (adRP), congenital stationary night blindness (CSNB), and autosomal recessive retinitis pigmentosa (arRP). For the latter, a single patient has been reported with a nonsense mutation at codon 249 on both alleles. Heterozygous carriers of missense mutations of rhodopsin develop either adRP or CSNB depending on the particular amino acid substitution. Four of the 9 siblings from a consanguineous marriage in southern India were reported the have arRP. Mutational screening and sequencing of the rhodopsin gene revealed a G-to-A transition of the first nucleotide at codon 150 in exon II, which alters glutamate to lysine. The E150K mutation was present in the 4 patients in homozygous form, whereas the parents and 2 of the siblings were heterozygotes. Two-point analysis produced a Zmax=3.46 at theta=0.00. Two unaffected siblings who are heterozygotes for the E150K mutation underwent a thorough ophthalmological and psychophysical examination. No clinical abnormalities were found although these individuals were over forty, whereas the onset of RP in their affected siblings was in the second decade. Collectively, both the genetic and clinical findings strongly suggest that the E150K mutation of rhodopsin is recessive in this family. Glu150 forms part of the CD cytoplasmic loop of rhodopsin, which has been implicated in the binding and activation of transducin. We speculate that E150K leads to RP because the mutant protein may be incapable of activating transducin. It is tempting to speculate that, in addition to mutations in the genes for rhodopsin and the {beta}-subunit of PDE, mutations in the genes for transducin may also result in arRP.

  17. Mutations in GRHL2 result in an autosomal-recessive ectodermal Dysplasia syndrome.

    PubMed

    Petrof, Gabriela; Nanda, Arti; Howden, Jake; Takeichi, Takuya; McMillan, James R; Aristodemou, Sophia; Ozoemena, Linda; Liu, Lu; South, Andrew P; Pourreyron, Celine; Dafou, Dimitra; Proudfoot, Laura E; Al-Ajmi, Hejab; Akiyama, Masashi; McLean, W H Irwin; Simpson, Michael A; Parsons, Maddy; McGrath, John A

    2014-09-01

    Grainyhead-like 2, encoded by GRHL2, is a member of a highly conserved family of transcription factors that play essential roles during epithelial development. Haploinsufficiency for GRHL2 has been implicated in autosomal-dominant deafness, but mutations have not yet been associated with any skin pathology. We investigated two unrelated Kuwaiti families in which a total of six individuals have had lifelong ectodermal defects. The clinical features comprised nail dystrophy or nail loss, marginal palmoplantar keratoderma, hypodontia, enamel hypoplasia, oral hyperpigmentation, and dysphagia. In addition, three individuals had sensorineural deafness, and three had bronchial asthma. Taken together, the features were consistent with an unusual autosomal-recessive ectodermal dysplasia syndrome. Because of consanguinity in both families, we used whole-exome sequencing to search for novel homozygous DNA variants and found GRHL2 mutations common to both families: affected subjects in one family were homozygous for c.1192T>C (p.Tyr398His) in exon 9, and subjects in the other family were homozygous for c.1445T>A (p.Ile482Lys) in exon 11. Immortalized keratinocytes (p.Ile482Lys) showed altered cell morphology, impaired tight junctions, adhesion defects, and cytoplasmic translocation of GRHL2. Whole-skin transcriptomic analysis (p.Ile482Lys) disclosed changes in genes implicated in networks of cell-cell and cell-matrix adhesion. Our clinical findings of an autosomal-recessive ectodermal dysplasia syndrome provide insight into the role of GRHL2 in skin development, homeostasis, and human disease.

  18. Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.

    PubMed

    Lise, Stefano; Clarkson, Yvonne; Perkins, Emma; Kwasniewska, Alexandra; Sadighi Akha, Elham; Schnekenberg, Ricardo Parolin; Suminaite, Daumante; Hope, Jilly; Baker, Ian; Gregory, Lorna; Green, Angie; Allan, Chris; Lamble, Sarah; Jayawant, Sandeep; Quaghebeur, Gerardine; Cader, M Zameel; Hughes, Sarah; Armstrong, Richard J E; Kanapin, Alexander; Rimmer, Andrew; Lunter, Gerton; Mathieson, Iain; Cazier, Jean-Baptiste; Buck, David; Taylor, Jenny C; Bentley, David; McVean, Gilean; Donnelly, Peter; Knight, Samantha J L; Jackson, Mandy; Ragoussis, Jiannis; Németh, Andrea H

    2012-01-01

    β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln. Using targeted capture and next-generation sequencing, we identified a homozygous stop codon in SPTBN2 in a consanguineous family in which childhood developmental ataxia co-segregates with cognitive impairment. The cognitive impairment could result from mutations in a second gene, but further analysis using whole-genome sequencing combined with SNP array analysis did not reveal any evidence of other mutations. We also examined a mouse knockout of β-III spectrin in which ataxia and progressive degeneration of cerebellar Purkinje cells has been previously reported and found morphological abnormalities in neurons from prefrontal cortex and deficits in object recognition tasks, consistent with the human cognitive phenotype. These data provide the first evidence that β-III spectrin plays an important role in cortical brain development and cognition, in addition to its function in the cerebellum; and we conclude that cognitive impairment is an integral part of this novel recessive ataxic syndrome, Spectrin-associated Autosomal Recessive Cerebellar Ataxia type 1 (SPARCA1). In addition, the identification of SPARCA1 and normal heterozygous carriers of the stop codon in SPTBN2 provides insights into the mechanism of molecular dominance in SCA5 and demonstrates that the cell-specific repertoire of spectrin subunits underlies a novel group of disorders, the neuronal spectrinopathies, which includes SCA5, SPARCA1, and a form of West syndrome.

  19. Glacier recession in Iceland and Austria

    NASA Technical Reports Server (NTRS)

    Hall, Dorothy K.; Williams, Richard S., Jr.; Bayr, Klaus J.

    1992-01-01

    It has been possible to measure glacier recession on the basis of Landsat data, in conjunction with comparisons of the magnitude of recession of a glacier margin with in situ measurements at fixed points along the same margin. Attention is presently given to the cases of Vatnajokull ice cap, in Iceland, and the Pasterze Glacier, in Austria, on the basis of satellite data from 1973-1987 and 1984-1990, respectively. Indications of a trend toward negative mass balance are noted. Nevertheless, while most of the world's small glaciers have been receding, some are advancing either due to local climate or the tidewater glacier cycle.

  20. Glacier recession in Iceland and Austria

    SciTech Connect

    Hall, D.K.; Williams, R.S. Jr.; Bayr, K.J. USGS, Reston, VA Keene State College, NH )

    1992-03-01

    It has been possible to measure glacier recession on the basis of Landsat data, in conjunction with comparisons of the magnitude of recession of a glacier margin with in situ measurements at fixed points along the same margin. Attention is presently given to the cases of Vatnajokull ice cap, in Iceland, and the Pasterze Glacier, in Austria, on the basis of satellite data from 1973-1987 and 1984-1990, respectively. Indications of a trend toward negative mass balance are noted. Nevertheless, while most of the world's small glaciers have been receding, some are advancing either due to local climate or the tidewater glacier cycle. 21 refs.

  1. Evidence for autosomal recessive inheritance in SPG3A caused by homozygosity for a novel ATL1 missense mutation

    PubMed Central

    Khan, Tahir Naeem; Klar, Joakim; Tariq, Muhammad; Anjum Baig, Shehla; Malik, Naveed Altaf; Yousaf, Raja; Baig, Shahid Mahmood; Dahl, Niklas

    2014-01-01

    Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of disorders characterized by progressive spasticity and weakness of the lower limbs. Autosomal dominant and ‘pure' forms of HSP account for ∼80% of cases in Western societies of whom 10% carry atlastin-1 (ATL1) gene mutations. We report on a large consanguineous family segregating six members with early onset HSP. The pedigree was compatible with both autosomal dominant and autosomal recessive inheritance. Whole-exome sequencing and segregation analysis revealed a homozygous novel missense variant c.353G>A, p.(Arg118Gln) in ATL1 in all six affected family members. Seven heterozygous carriers, five females and two males, showed no clinical signs of HSP with the exception of sub-clinically reduced vibration sensation in one adult female. Our combined findings show that homozygosity for the ATL1 missense variant remains the only plausible cause of HSP, whereas heterozygous carriers are asymptomatic. This apparent autosomal recessive inheritance adds to the clinical complexity of spastic paraplegia 3A and calls for caution using directed genetic screening in HSP. PMID:24473461

  2. Novel Deletion of SERPINF1 Causes Autosomal Recessive Osteogenesis Imperfecta Type VI in Two Brazilian Families

    PubMed Central

    Moldenhauer Minillo, Renata; Sobreira, Nara; de Fatima de Faria Soares, Maria; Jurgens, Julie; Ling, Hua; Hetrick, Kurt N.; Doheny, Kimberly F.; Valle, David; Brunoni, Decio; Alvarez Perez, Ana B.

    2014-01-01

    Autosomal recessive osteogenesis imperfecta (OI) accounts for 10% of all OI cases, and, currently, mutations in 10 genes (CRTAP, LEPRE1, PPIB, SERPINH1, FKBP10, SERPINF1, SP7, BMP1, TMEM38B, and WNT1) are known to be responsible for this form of the disease. PEDF is a secreted glycoprotein of the serpin superfamily that maintains bone homeostasis and regulates osteoid mineralization, and it is encoded by SERPINF1, currently associated with OI type VI (MIM 172860). Here, we report a consanguineous Brazilian family in which multiple individuals from at least 4 generations are affected with a severe form of OI, and we also report an unrelated individual from the same small city in Brazil with a similar but more severe phenotype. In both families the same homozygous SERPINF1 19-bp deletion was identified which is not known in the literature yet. We described intra- and interfamilial clinical and radiological phenotypic variability of OI type VI caused by the same homozygous SERPINF1 19-bp deletion and suggest a founder effect. Furthermore, the SERPINF1 genotypes/phenotypes reported so far in the literature are reviewed. PMID:25565926

  3. Mutations in SNX14 Cause a Distinctive Autosomal-Recessive Cerebellar Ataxia and Intellectual Disability Syndrome

    PubMed Central

    Thomas, Anna C.; Williams, Hywel; Setó-Salvia, Núria; Bacchelli, Chiara; Jenkins, Dagan; O’Sullivan, Mary; Mengrelis, Konstantinos; Ishida, Miho; Ocaka, Louise; Chanudet, Estelle; James, Chela; Lescai, Francesco; Anderson, Glenn; Morrogh, Deborah; Ryten, Mina; Duncan, Andrew J.; Pai, Yun Jin; Saraiva, Jorge M.; Ramos, Fabiana; Farren, Bernadette; Saunders, Dawn; Vernay, Bertrand; Gissen, Paul; Straatmaan-Iwanowska, Anna; Baas, Frank; Wood, Nicholas W.; Hersheson, Joshua; Houlden, Henry; Hurst, Jane; Scott, Richard; Bitner-Glindzicz, Maria; Moore, Gudrun E.; Sousa, Sérgio B.; Stanier, Philip

    2014-01-01

    Intellectual disability and cerebellar atrophy occur together in a large number of genetic conditions and are frequently associated with microcephaly and/or epilepsy. Here we report the identification of causal mutations in Sorting Nexin 14 (SNX14) found in seven affected individuals from three unrelated consanguineous families who presented with recessively inherited moderate-severe intellectual disability, cerebellar ataxia, early-onset cerebellar atrophy, sensorineural hearing loss, and the distinctive association of progressively coarsening facial features, relative macrocephaly, and the absence of seizures. We used homozygosity mapping and whole-exome sequencing to identify a homozygous nonsense mutation and an in-frame multiexon deletion in two families. A homozygous splice site mutation was identified by Sanger sequencing of SNX14 in a third family, selected purely by phenotypic similarity. This discovery confirms that these characteristic features represent a distinct and recognizable syndrome. SNX14 encodes a cellular protein containing Phox (PX) and regulator of G protein signaling (RGS) domains. Weighted gene coexpression network analysis predicts that SNX14 is highly coexpressed with genes involved in cellular protein metabolism and vesicle-mediated transport. All three mutations either directly affected the PX domain or diminished SNX14 levels, implicating a loss of normal cellular function. This manifested as increased cytoplasmic vacuolation as observed in cultured fibroblasts. Our findings indicate an essential role for SNX14 in neural development and function, particularly in development and maturation of the cerebellum. PMID:25439728

  4. Autosomal recessive mental retardation syndrome with anterior maxillary protrusion and strabismus: MRAMS syndrome.

    PubMed

    Basel-Vanagaite, Lina; Rainshtein, Limor; Inbar, Dov; Gothelf, Doron; Hennekam, Raoul; Straussberg, Rachel

    2007-08-01

    We report on a family in whom the combination of mental retardation (MR), anterior maxillary protrusion, and strabismus segregates. The healthy, consanguineous parents (first cousins) of Israeli-Arab descent had 11 children, 7 of whom (5 girls) were affected. They all had severe MR. Six of the seven had anterior maxillary protrusion with vertical maxillary excess, open bite, and prominent crowded teeth. None of the sibs with normal intelligence had jaw or dental anomalies. The child with MR but without a jaw anomaly was somewhat less severely retarded, had seizures and severe psychosis, which may point to his having a separate disorder. Biochemical and neurological studies, including brain MRI and standard cytogenetic studies, yielded normal results; fragile X was excluded, no subtelomeric rearrangements were detectable, and X-inactivation studies in the mother showed random inactivation. We have been unable to find a similar disorder in the literature, and suggest that this is a hitherto unreported autosomal recessive disorder, which we propose to name MRAMS (mental retardation, anterior maxillary protrusion, and strabismus).

  5. Responding to the increased genetic risk associated with customary consanguineous marriage among minority ethnic populations: lessons from local innovations in England.

    PubMed

    Salway, Sarah; Ali, Parveen; Ratcliffe, Giles; Such, Elizabeth; Khan, Nasaim; Kingston, Helen; Quarrell, Oliver

    2016-07-01

    Populations practising customary consanguineous marriage have a higher incidence of autosomal recessive genetic disorders than those in which reproductive partners are usually unrelated. In the absence of any national-level response, English service developments to address the additional needs of families living with or at risk of such disorders have been locally led. These interventions remain in their infancy here, as elsewhere in Europe, and important questions remain regarding how appropriate, effective and sustainable responses can be operationalised in practice. This formative service review employed four local case studies together with wider consultation exercises over a 4-year period (2011-2015) to document recent responses to this area of need, issues arising and lessons to inform future work. Service components included the following: enhancements to genetic services to provide family-centred, culturally competent approaches to counselling and testing; community genetic literacy approaches; and capacity development among health professionals. Local approaches were, however, very varied in their detail, scope, level of investment and longevity. The provisions of culturally competent genetic counselling services and community-level genetic literacy interventions were generally well received by those who accessed them. Coordinated action across all service components appeared important for an effective service, but healthcare professionals, particularly general practitioners, were often difficult to engage in this agenda. An evaluative culture and engagement in a wider community of practice had supported service development across sites. However, sustaining investment was challenging, particularly where new services were not well integrated into core provision and where commissioning was driven by expectations of short-term reductions in infant mortality and disability.

  6. Responding to the increased genetic risk associated with customary consanguineous marriage among minority ethnic populations: lessons from local innovations in England.

    PubMed

    Salway, Sarah; Ali, Parveen; Ratcliffe, Giles; Such, Elizabeth; Khan, Nasaim; Kingston, Helen; Quarrell, Oliver

    2016-07-01

    Populations practising customary consanguineous marriage have a higher incidence of autosomal recessive genetic disorders than those in which reproductive partners are usually unrelated. In the absence of any national-level response, English service developments to address the additional needs of families living with or at risk of such disorders have been locally led. These interventions remain in their infancy here, as elsewhere in Europe, and important questions remain regarding how appropriate, effective and sustainable responses can be operationalised in practice. This formative service review employed four local case studies together with wider consultation exercises over a 4-year period (2011-2015) to document recent responses to this area of need, issues arising and lessons to inform future work. Service components included the following: enhancements to genetic services to provide family-centred, culturally competent approaches to counselling and testing; community genetic literacy approaches; and capacity development among health professionals. Local approaches were, however, very varied in their detail, scope, level of investment and longevity. The provisions of culturally competent genetic counselling services and community-level genetic literacy interventions were generally well received by those who accessed them. Coordinated action across all service components appeared important for an effective service, but healthcare professionals, particularly general practitioners, were often difficult to engage in this agenda. An evaluative culture and engagement in a wider community of practice had supported service development across sites. However, sustaining investment was challenging, particularly where new services were not well integrated into core provision and where commissioning was driven by expectations of short-term reductions in infant mortality and disability. PMID:27311843

  7. An overview of the predictors of depression among adult Pakistani women.

    PubMed

    Zahidie, Aysha; Jamali, Tanzil

    2013-08-01

    Diseases of women that are due to their gender specific roles and responsibilities result from cultural and social factors prevalent in the environs. World Health Organization has put special emphasis on research need regarding gender related factors for diseases disproportionately affecting women in developing countries. The objective of this write up was to determine the prevalence of depression and the associated risk factors among adult women in Pakistan. PubMed was searched using key words depression, risk factors, women and Pakistan. Out of 20 initially retrieved articles, 12 were directly related to depression and its risk factors among Pakistani women within Pakistani geographical context. Women in Pakistan are vulnerable to poor mental health due to marriage related issues, domestic violence, verbal or physical abuse by in-laws, stressful life and poor social conditions. Women in their perinatal period are more at risk of depression due to pregnancy related concerns. PMID:23930875

  8. University students perspective on polio vaccination--ruse or realistic need for Pakistani children?

    PubMed

    Shaikh, Masood Ali; Kamal, Anila; Naqvi, Irum

    2014-06-01

    Polio vaccinators and law enforcement officials protecting them, have been killed in the line of duty since 2012 in Pakistan. This study was conducted to determine the opinions of university students in Islamabad and Rawalpindi, regarding the importance of polio vaccination, and the role of international donor agencies. Nine hundred forty-six students participated in this study; 833 (88.1%) students thought that polio is a public health problem in the country, and 815 (86.2%) thought that polio vaccination prevents polio in children. About a quarter of respondents thought that Pakistanis as well as non-Pakistanis working for either international nongovernmental organizations or United Nations agencies are spies working for the Western governments or their spy agencies. An appalling 300 (31.7%) respondents replied as either affirmatively or 'don't know' to the question whether killing of polio vaccinators is justified. PMID:25252493

  9. An overview of the predictors of depression among adult Pakistani women.

    PubMed

    Zahidie, Aysha; Jamali, Tanzil

    2013-08-01

    Diseases of women that are due to their gender specific roles and responsibilities result from cultural and social factors prevalent in the environs. World Health Organization has put special emphasis on research need regarding gender related factors for diseases disproportionately affecting women in developing countries. The objective of this write up was to determine the prevalence of depression and the associated risk factors among adult women in Pakistan. PubMed was searched using key words depression, risk factors, women and Pakistan. Out of 20 initially retrieved articles, 12 were directly related to depression and its risk factors among Pakistani women within Pakistani geographical context. Women in Pakistan are vulnerable to poor mental health due to marriage related issues, domestic violence, verbal or physical abuse by in-laws, stressful life and poor social conditions. Women in their perinatal period are more at risk of depression due to pregnancy related concerns.

  10. Muslim Spirituality, Religious Coping, and Reactions to Terrorism Among Pakistani University Students.

    PubMed

    Khan, Ziasma Haneef; Watson, P J; Chen, Zhuo

    2016-12-01

    Pakistani Muslim university students (N = 207) displayed Personal Distress, Public Distress, and Personal Defeat Reactions to Terrorism. All three reactions predicted poorer mental health with Personal Defeat being especially disturbed in its adjustment implications. In line with the assumptions of coping theory, scores on the Negative Religious Coping Scale correlated positively with Personal Distress and with Personal Defeat. However, Positive Religious Coping, the spirituality of Muslim Experiential Religiousness, and the Intrinsic and Extrinsic Personal Religious Orientations exhibited positive rather than the expected negative linkages with Personal Distress and Public Distress. Muslim Experiential Religiousness moderated associations of Positive and Negative Religious Coping with Public Distress. When spirituality was high, these relationships were negative. When spirituality was low, they became positive. These data documented the negative impacts that terrorism can have on Pakistanis and suggested that Muslim religious commitments may have an important role to play in resisting those influences.

  11. Complete genome sequencing and comparative analysis of three dengue virus type 2 Pakistani isolates.

    PubMed

    Akram, Madiha; Idrees, Muhammad

    2016-03-01

    Dengue is currently one of the most important arthropod borne human viral diseases caused by a flavivirus named as dengue virus. It is now endemic in Pakistan since many dengue fever outbreaks have been observed in Pakistan during the last three decades. Major serotype of dengue virus circulating in Pakistan is serotype 2. Complete genome sequences of three Pakistani dengue virus serotype 2 isolates were generated. Analysis of complete genome sequences showed that Pakistani isolates of dengue virus serotype 2 belonged to cosmopolitan genotype. This study identifies a number of amino acid substitutions that were introduced in local dengue virus serotype 2 isolate over the years. The study provides a significant insight into the evolution of serotype 2 of dengue virus in Pakistan. This is the first report of complete genome sequence information of dengue virus from the most recent outbreak (2013) in Punjab, Pakistan.

  12. Experiences of outreach workers in promoting smoking cessation to Bangladeshi and Pakistani men: longitudinal qualitative evaluation

    PubMed Central

    2011-01-01

    Background Despite having high smoking rates, there have been few tailored cessation programmes for male Bangladeshi and Pakistani smokers in the UK. We report on a qualitative evaluation of a community-based, outreach worker delivered, intervention that aimed to increase uptake of NHS smoking cessation services and tailor services to meet the needs of Bangladeshi and Pakistani men. Methods This was a longitudinal, qualitative study, nested within a phase II cluster randomised controlled trial of a complex intervention. We explored the perspectives and experiences of five outreach workers, two stop smoking service managers and a specialist stop smoking advisor. Data were collected through focus group discussions, weekly diaries, observations of management meetings, shadowing of outreach workers, and one-to-one interviews with outreach workers and their managers. Analysis was undertaken using a modified Framework approach. Results Outreach workers promoted cessation services by word of mouth on the streets, in health service premises, in local businesses and at a wide range of community events. They emphasised the reasons for cessation, especially health effects, financial implications, and the impact of smoking on the family. Many smokers agreed to be referred to cessation services, but few attended, this in part being explained by concerns about the relative inflexibility of existing service provision. Although outreach workers successfully expanded service reach, they faced the challenges of perceived lack of awareness of the health risks associated with smoking in older smokers and apathy in younger smokers. These were compounded by perceptions of "lip service" being given to their role by community organisations and tensions both amongst the outreach workers and with the wider management team. Conclusions Outreach workers expanded reach of the service through taking it to diverse locations of relevance to Pakistani and Bangladeshi communities. The optimum

  13. British and Pakistani children's understanding of death: cultural and developmental influences.

    PubMed

    Panagiotaki, Georgia; Nobes, Gavin; Ashraf, Aisha; Aubby, Herjit

    2015-03-01

    This study explored British and Pakistani 4- to 7-year-olds' (N = 188) understanding of death. The aim was to examine possible influences on the acquisition of the subcomponents of the death concept by investigating how they are understood by children of different ages and cultural and religious backgrounds. Three groups of children were compared: White British and British Muslim living in London, and Pakistani Muslim living in rural Pakistan. In line with previous research (Slaughter, 2005, Aust. Psychol., 40(3), 179), irreversibility of death was one of the first subcomponents to be acquired, while causality was the last. The two groups of British children shared many similarities in their understanding of inevitability, applicability, irreversibility, and cessation. Pakistani Muslim children understood irreversibility earlier than did children in both British groups. In all three cultural groups, children's responses demonstrated very limited understanding of causality. Our findings support the view that aspects of a mature understanding of death develop between the ages of 4 and 7 years and that the process of understanding death as a biological event is, to a great extent, universal. They also suggest that aspects of children's reasoning are influenced by culturally specific experiences, particularly those arising from living in rural versus urban settings.

  14. Genetic link of type 1 diabetes susceptibility loci with rheumatoid arthritis in Pakistani patients.

    PubMed

    Kiani, Aysha Karim; Jahangir, Sidrah; Jahngir, Sidrah; John, Peter; Bhatti, Attya; Zia, Asima; Wang, Xingbin; Demirci, F Yesim; Kamboh, M Ilyas

    2015-06-01

    Rheumatoid arthritis (RA) and type 1 diabetes (T1D) are two autoimmune disorders that have been reported to co-occur in the same subjects or in different subjects from the same family. This suggests the sharing of disease susceptibility loci between RA and T1D. This study was aimed to find out such susceptibility loci that are common in both T1D and RA in Pakistani population. A total of 366 Pakistanis comprising related and unrelated RA cases and controls were recruited. Blood samples were collected from all patients followed by DNA isolation. Thirty-one single-nucleotide polymorphisms (SNPs) previously reported to be associated with T1D were genotyped in RA cases and controls using TaqMan SNP genotyping assays. Data was analyzed using FamCC software. We have identified seven SNP associations that survived multiple testing corrections using false discovery rate: SKAP2/rs7804356 (p = 2.47E-04), GLIS3/rs7020673 (p = 2.86E-04), GSDMB/rs2290400 (p = 23.48E-04), BACH2/rs11755527 (p = 9.16E-04), C6orf173/ rs9388489 (p = 3.11E-03), PRKCQ/DKFZp667F0711/ rs947474 (p = 4.53E-03), and DLK1/ rs941576 (p = 9.51E-03). Our results support the presence of overlapping loci between RA and T1D in Pakistani patients. PMID:25904084

  15. Identities in the third space? Solidity, elasticity and resilience amongst young British Pakistani Muslims.

    PubMed

    Mythen, Gabe

    2012-09-01

    Over the last decade the issue of identity has been prevalent in discussions about British Muslims, with the events of 9/11 serving as a touchstone for media debates about religious, national and cultural affiliations. The 7/7 terrorist attacks in the UK led to young British Pakistanis being subjected to intense public and institutional scrutiny and wider political concerns being expressed about the failure of multiculturalism. Young British Pakistanis have thus had to negotiate and maintain their identities in an environment in which they have been defined as a threat to national security whilst simultaneously being pressurized to align with 'core British values'. Within this context, we convey the findings of a qualitative study involving British Pakistanis living in the North-west of England. In presenting the experiences and perspectives of participants, three interconnected processes salient to the maintenance of identity are delineated: solidity, elasticity and resilience. Having unpacked these processes, we draw upon Bhabha's third space thesis to explore the political potentiality of and the limits to hybridic identities.

  16. Weathering the Recession in College Health

    ERIC Educational Resources Information Center

    Christmas, William A.

    2010-01-01

    The current global recession has increased personal stress levels throughout our society. With dwindling resources, institutions of higher learning are especially prone to budgetary cutbacks during such periods. Based on 22 years of experience as a health service director, the author offers some personal insights in the hope that they will help…

  17. [Periodontology and esthetics: the gingival recession].

    PubMed

    Corba, N H

    1991-06-01

    Gingival recessions are regarded by many people as an esthetical problem. Successively the etiology, the significance and the indications for therapy are discussed. Different kinds of therapy such as oral hygiene instruction, the free gingival graft and various pedicle grafts are explained. Finally it is advocated that surgical kinds of therapy have to be applied with reservedness.

  18. The Recession and Education: Seize New Opportunities!

    ERIC Educational Resources Information Center

    Haskvitz, Alan

    2011-01-01

    The teaching profession has long been thought of as recession proof. Indeed, that may have been one of the reasons why teachers took far lower starting salaries right out of college. Perhaps the greatest common feature of teachers, besides their desire to serve society in a humanitarian way, may be the lack of risk-taking the occupation previously…

  19. Shop Steward Resistance in the Recession.

    ERIC Educational Resources Information Center

    Spencer, Bruce

    1985-01-01

    This article draws on work carried out in a British brewery, refutes the claim that the recession has made trade unions irrelevant to managerial concerns, and argues that cohesive, factor-based shop steward organization can resist a management onslaught. (Author/CT)

  20. The effect of recessions on gambling expenditures.

    PubMed

    Horváth, Csilla; Paap, Richard

    2012-12-01

    This article examines the influence of the business cycle on expenditures of three major types of legalized gambling activities: Casino gambling, lottery, and pari-mutuel wagering. Empirical results are obtained using monthly aggregated US per capita consumption time series for the period 1959.01-2010.08. Among the three gambling activities only lottery consumption appears to be recession-proof. This series is characterized by a vast and solid growth that exceeds the growth in income and the growth in other gambling sectors. Casino gambling expenditures show a positive growth during expansions and no growth during recessions. Hence, the loss in income during recessions affects casino gambling. However, income shocks which are not directly related to the business cycle do not influence casino gambling expenditures. Pari-mutuel wagering displays an overall negative trend and its average growth rate is smaller than the growth in income, especially during recessions. The findings of this article provide important implications for the gambling industry and for local governments.

  1. Recession curbs gas pipeline construction costs

    SciTech Connect

    Morgan, J.M.

    1983-01-24

    This paper shows how after 5 yrs. of inflation, gas pipeline construction costs have finally felt the effects of a severe building recession. First quarter (1982) construction activity, compressor equipment and drive units, and high-pressure gas-station piping are discussed. Graphs of OGJ-Morgan composite gas pipeline cost, and gas pipeline cost component indexes are presented.

  2. Gender Differences during Recess in Elementary Schools.

    ERIC Educational Resources Information Center

    Twarek, Linda S.; George, Halley S.

    A study examined the differences in what boys and girls choose, or are free to choose, to do on the playground during recess. Given the apparent problem that boys dominate the playground area, leaving girls on the perimeter, it was hypothesized that girls engage in passive, non-competitive, small group activities, whereas boys engage in…

  3. Nevada, the Great Recession, and Education

    ERIC Educational Resources Information Center

    Verstegen, Deborah A.

    2013-01-01

    The impact of the Great Recession and its aftermath has been devastating in Nevada, especially for public education. This article discusses the budget shortfalls and the impact of the economic crisis in Nevada using case study methodology. It provides a review of documents, including Governor Gibbon's proposals for the public K-12 education system…

  4. Weathering the recession in college health.

    PubMed

    Christmas, William A

    2010-01-01

    The current global recession has increased personal stress levels throughout our society. With dwindling resources, institutions of higher learning are especially prone to budgetary cutbacks during such periods. Based on 22 years of experience as a health service director, the author offers some personal insights in the hope that they will help colleagues cope with the current situation.

  5. Testing Faces Ups and Downs Amid Recession

    ERIC Educational Resources Information Center

    Sawchuk, Stephen

    2009-01-01

    As the recession crimps education budgets, states are beginning to pare the number of standardized tests they give, particularly those that no longer factor into state or federal accountability decisions. At the district level, though, it's a different story. Despite pressure not to cut staffing and programs, many districts are preserving local…

  6. On the adaptive origins and maladaptive consequences of human inbreeding: parasite prevalence, immune functioning, and consanguineous marriage.

    PubMed

    Hoben, Ashley D; Buunk, Abraham P; Fincher, Corey L; Thornhill, Randy; Schaller, Mark

    2010-11-13

    We propose that consanguineous marriages arise adaptively in response to high parasite prevalence and function to maintain coadapted gene complexes and associated local adaptation that defend against local pathogens. Therefore, a greater prevalence of inbreeding by consanguineous marriage is expected in geographical regions that historically have had high levels of disease-causing parasites. Eventually such marriages may, under the contemporary high movement of people with modern transportation, jeopardize the immunity of those who practice inbreeding as this leads to an increased susceptibility to novel pathogens. Therefore, a greater frequency of inbreeding is expected to predict higher levels of contemporary mortality and morbidity from infectious diseases. This parasite model of human inbreeding was supported by an analysis involving 72 countries worldwide. We found that historically high levels of pathogen prevalence were related positively to the proportion of consanguineous marriages, and that a higher prevalence of such marriages was associated with higher contemporary mortality and morbidity due to pathogens. Our study addresses plausible alternative explanations. The results suggest that consanguineous marriage is an adaptive consequence of historical pathogen ecologies, but is maladaptive in contemporary disease ecologies.

  7. Mutations in C8orf37, encoding a ciliary protein, are associated with autosomal-recessive retinal dystrophies with early macular involvement.

    PubMed

    Estrada-Cuzcano, Alejandro; Neveling, Kornelia; Kohl, Susanne; Banin, Eyal; Rotenstreich, Ygal; Sharon, Dror; Falik-Zaccai, Tzipora C; Hipp, Stephanie; Roepman, Ronald; Wissinger, Bernd; Letteboer, Stef J F; Mans, Dorus A; Blokland, Ellen A W; Kwint, Michael P; Gijsen, Sabine J; van Huet, Ramon A C; Collin, Rob W J; Scheffer, H; Veltman, Joris A; Zrenner, Eberhart; den Hollander, Anneke I; Klevering, B Jeroen; Cremers, Frans P M

    2012-01-13

    Cone-rod dystrophy (CRD) and retinitis pigmentosa (RP) are clinically and genetically overlapping heterogeneous retinal dystrophies. By using homozygosity mapping in an individual with autosomal-recessive (ar) RP from a consanguineous family, we identified three sizeable homozygous regions, together encompassing 46 Mb. Next-generation sequencing of all exons, flanking intron sequences, microRNAs, and other highly conserved genomic elements in these three regions revealed a homozygous nonsense mutation (c.497T>A [p.Leu166(∗)]) in C8orf37, located on chromosome 8q22.1. This mutation was not present in 150 ethnically matched control individuals, single-nucleotide polymorphism databases, or the 1000 Genomes database. Immunohistochemical studies revealed C8orf37 localization at the base of the primary cilium of human retinal pigment epithelium cells and at the base of connecting cilia of mouse photoreceptors. C8orf37 sequence analysis of individuals who had retinal dystrophy and carried conspicuously large homozygous regions encompassing C8orf37 revealed a homozygous splice-site mutation (c.156-2A>G) in two siblings of a consanguineous family and homozygous missense mutations (c.529C>T [p.Arg177Trp]; c.545A>G [p.Gln182Arg]) in siblings of two other consanguineous families. The missense mutations affect highly conserved amino acids, and in silico analyses predicted that both variants are probably pathogenic. Clinical assessment revealed CRD in four individuals and RP with early macular involvement in two individuals. The two CRD siblings with the c.156-2A>G mutation also showed unilateral postaxial polydactyly. These results underline the importance of disrupted ciliary processes in the pathogenesis of retinal dystrophies.

  8. Consanguineous marriages and marriage payment: a study among three south Indian caste groups.

    PubMed

    Reddy, P G

    1988-01-01

    The present study aims at understanding the interrelations between consanguineous marriages and marriage payment. The data are collected from three castes inhabiting two regions of Nellore district, Andhra Pradesh, South India. It is evident from the study that the dowry system is more prevalent among higher castes, while the bride wealth system is more common among the lower castes in the hierarchy. Further, it can be seen that the dowry system is more prevalent in developed regions, while bride-wealth is more common in backward regions. Marriage payment is found to be less common in close kin marriages than in unrelated marriages. Most of the uncle-niece marriages are without any marriage payment, in all the castes. However, most of the matrilateral cross-cousin and patrilateral cross-cousin marriages are also without any marriage payment in the Devanga.

  9. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy.

    PubMed

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A; Hernandez, Dena G; Heutink, Peter; Gibbs, J Raphael; Hardy, John; Wood, Nicholas W; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis

    2016-03-01

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. PMID:26942284

  10. Loss of VPS13C Function in Autosomal-Recessive Parkinsonism Causes Mitochondrial Dysfunction and Increases PINK1/Parkin-Dependent Mitophagy

    PubMed Central

    Lesage, Suzanne; Drouet, Valérie; Majounie, Elisa; Deramecourt, Vincent; Jacoupy, Maxime; Nicolas, Aude; Cormier-Dequaire, Florence; Hassoun, Sidi Mohamed; Pujol, Claire; Ciura, Sorana; Erpapazoglou, Zoi; Usenko, Tatiana; Maurage, Claude-Alain; Sahbatou, Mourad; Liebau, Stefan; Ding, Jinhui; Bilgic, Basar; Emre, Murat; Erginel-Unaltuna, Nihan; Guven, Gamze; Tison, François; Tranchant, Christine; Vidailhet, Marie; Corvol, Jean-Christophe; Krack, Paul; Leutenegger, Anne-Louise; Nalls, Michael A.; Hernandez, Dena G.; Heutink, Peter; Gibbs, J. Raphael; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Durr, Alexandra; Deleuze, Jean-François; Tazir, Meriem; Destée, Alain; Lohmann, Ebba; Kabashi, Edor; Singleton, Andrew; Corti, Olga; Brice, Alexis; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Viallet, François; Brice, Alexis; Lesage, Suzanne; Majounie, Elisa; Tison, François; Vidailhet, Marie; Corvol, Jean Christophe; Nalls, Michael A.; Hernandez, Dena G.; Gibbs, J. Raphael; Dürr, Alexandra; Arepalli, Sampath; Barker, Roger A.; Ben-Shlomo, Yoav; Berg, Daniela; Bettella, Francesco; Bhatia, Kailash; de Bie, Rob M.A.; Biffi, Alessandro; Bloem, Bastiaan R.; Bochdanovits, Zoltan; Bonin, Michael; Lesage, Suzanne; Tison, François; Vidailhet, Marie; Corvol, Jean-Christophe; Agid, Yves; Anheim, Mathieu; Bonnet, Anne-Marie; Borg, Michel; Broussolle, Emmanuel; Damier, Philippe; Destée, Alain; Dürr, Alexandra; Durif, Franck; Krack, Paul; Klebe, Stephan; Lohmann, Ebba; Martinez, Maria; Pollak, Pierre; Rascol, Olivier; Tranchant, Christine; Vérin, Marc; Bras, Jose M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Dong, Jing; Durif, Frank; Edkins, Sarah; Escott-Price, Valentina; Evans, Jonathan R.; Foltynie, Thomas; Gao, Jianjun; Gardner, Michelle; Goate, Alison; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holmans, Peter; Holton, Janice; Hu, Michèle; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jónsson, Pálmi V.; Kilarski, Laura L.; Jansen, Iris E.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; Lubbe, Steven; Lungu, Codrin; Martinez, María; Mätzler, Walter; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morrison, Karen E.; Mudanohwo, Ese; O’Sullivan, Sean S.; Owen, Michael J.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Plagnol, Vincent; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Saad, Mohamad; Simón-Sánchez, Javier; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Schulte, Claudia; Sharma, Manu; Shaw, Karen; Sheerin, Una-Marie; Shoulson, Ira; Shulman, Joshua; Sidransky, Ellen; Spencer, Chris C.A.; Stefánsson, Hreinn; Stefánsson, Kári; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Wurster, Isabel; Williams, Nigel; Morris, Huw R.; Heutink, Peter; Hardy, John; Wood, Nicholas W.; Gasser, Thomas; Singleton, Andrew B.; Brice, Alexis

    2016-01-01

    Autosomal-recessive early-onset parkinsonism is clinically and genetically heterogeneous. The genetic causes of approximately 50% of autosomal-recessive early-onset forms of Parkinson disease (PD) remain to be elucidated. Homozygozity mapping and exome sequencing in 62 isolated individuals with early-onset parkinsonism and confirmed consanguinity followed by data mining in the exomes of 1,348 PD-affected individuals identified, in three isolated subjects, homozygous or compound heterozygous truncating mutations in vacuolar protein sorting 13C (VPS13C). VPS13C mutations are associated with a distinct form of early-onset parkinsonism characterized by rapid and severe disease progression and early cognitive decline; the pathological features were striking and reminiscent of diffuse Lewy body disease. In cell models, VPS13C partly localized to the outer membrane of mitochondria. Silencing of VPS13C was associated with lower mitochondrial membrane potential, mitochondrial fragmentation, increased respiration rates, exacerbated PINK1/Parkin-dependent mitophagy, and transcriptional upregulation of PARK2 in response to mitochondrial damage. This work suggests that loss of function of VPS13C is a cause of autosomal-recessive early-onset parkinsonism with a distinctive phenotype of rapid and severe progression. PMID:26942284

  11. Genetics Home Reference: autosomal recessive cerebellar ataxia type 1

    MedlinePlus

    ... Health Conditions ARCA1 autosomal recessive cerebellar ataxia type 1 Enable Javascript to view the expand/collapse boxes. ... Close All Description Autosomal recessive cerebellar ataxia type 1 ( ARCA1 ) is a condition characterized by progressive problems ...

  12. A novel frameshift mutation in KCNQ4 in a family with autosomal recessive non-syndromic hearing loss.

    PubMed

    Wasano, Koichiro; Mutai, Hideki; Obuchi, Chie; Masuda, Sawako; Matsunaga, Tatsuo

    2015-08-01

    Mutation of KCNQ4 has been reported to cause autosomal dominant non-syndromic hearing loss (DFNA2A) that usually presents as progressive hearing loss starting from mild to moderate hearing loss during childhood. Here, we identified a novel KCNQ4 mutation, c.1044_1051del8, in a family with autosomal recessive non-syndromic hearing loss. The proband was homozygous for the mutation and was born to consanguineous parents; she showed severe hearing loss that was either congenital or of early childhood onset. The proband had a sister who was heterozygous for the mutation but showed normal hearing. The mutation caused a frameshift that eliminated most of the cytoplasmic C-terminus, including the A-domain, which has an important role for protein tetramerization, and the B-segment, which is a binding site for calmodulin (CaM) that regulates channel function via Ca ions. The fact that the heterozygote had normal hearing indicates that sufficient tetramerization and CaM binding sites were present to preserve a normal phenotype even when only half the proteins contained an A-domain and B-segment. On the other hand, the severe hearing loss in the homozygote suggests that complete loss of the A-domain and B-segment in the protein caused loss of function due to the failure of tetramer formation and CaM binding. This family suggests that some KCNQ4 mutations can cause autosomal recessive hearing loss with more severe phenotype in addition to autosomal dominant hearing loss with milder phenotype. This genotype-phenotype correlation is analogous to that in KCNQ1 which causes autosomal dominant hereditary long QT syndrome 1 with milder phenotype and the autosomal recessive Jervell and Lange-Nielsen syndrome 1 with more severe phenotype due to deletion of the cytoplasmic C-terminus of the potassium channel.

  13. A systematic search for linkage with nonsyndromic recessive deafness in two large Middle Eastern inbred kindreds excludes more than 30% of the genome

    SciTech Connect

    Weiss, S.; Korostishevsky, M.; Frydman, M.

    1994-09-01

    It has been estimated that as many as 35 loci may individually cause autosomal recessive non-syndromic deafness. The extreme genetic heterogeneity, limited clinical differentiation and phenotypic assortative mating in many western countries make many families unsuitable for genetic linkage studies. Recently the first of those loci was mapped (to 13q) in two consanguineous families from northern Tunisia. We are studying two large highly consanguineous Middle Eastern kindreds (a total of 26 deaf in 98 sampled individuals). Examination in each family showed no evidence of clinical heterogeneity and indicated an uncomplicated profound bilateral sensorineural deafness. We have been able to exclude the 13q locus as the cause of deafness in each kindred and have also excluded such `candidate` loci as regions as those causing Usher`s syndrome type 1 (11q13)(11p), Usher`s syndrome type II (1q32-q41), Waardenburg syndrome type I (2q37), branchio-oto-renal syndrome (8q12-q13), Monge`s deafness (5q31), and Treacher Collins syndrome (5q31.3-q33.3). To date, no lod scores greater than 1 have been obtained in either kindred using 150 RFLT`s, VNTR`s and highly polymorphic microsatellite markers (CA repeats and tetranucleotides). By Morton`s criterion a minimum of 30% of the autosomal genome can be excluded for each kindred separately.

  14. Two New Loci for Autosomal Recessive Ichthyosis on Chromosomes 3p21 and 19p12-q12 and Evidence for Further Genetic Heterogeneity

    PubMed Central

    Fischer, Judith; Faure, Alexandra; Bouadjar, Bakar; Blanchet-Bardon, Claudine; Karaduman, Aysen; Thomas, Isabelle; Emre, Serap; Cure, Susan; Özgüc, Meral; Weissenbach, Jean; Prud'homme, Jean-François

    2000-01-01

    Autosomal recessive ichthyosis (ARI) includes a heterogeneous group of disorders of keratinization characterized by desquamation over the whole body. Two forms largely limited to the skin have been defined: lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). A first gene for LI, transglutaminase TGM1, has been identified on chromosome 14, and a second one has been localized on chromosome 2. In a genomewide scan of nine large consanguineous families, using homozygosity mapping, two new loci for ARI were found, one for a lamellar form in a 6-cM interval on chromosome 19 and a second for an erythrodermic form in a 7.7-cM interval on chromosome 3. Linkage to one of the four loci could be demonstrated in more than half of 51 consanguineous families, most of them from the Mediterranean basin. All four loci could be excluded in the others, implying further genetic heterogeneity in this disorder. Multipoint linkage analysis gave maximal LOD scores of 11.25 at locus D19S566 and 8.53 at locus D3S3564. PMID:10712205

  15. A missense mutation in ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), causes an autosomal recessive neurocutaneous syndrome.

    PubMed

    Bicknell, Louise S; Pitt, James; Aftimos, Salim; Ramadas, Ram; Maw, Marion A; Robertson, Stephen P

    2008-10-01

    There are several rare syndromes combining wrinkled, redundant skin and neurological abnormalities. Although phenotypic overlap between conditions has suggested that some might be allelic to one another, the aetiology for many of them remains unknown. A consanguineous New Zealand Maori family has been characterised that segregates an autosomal recessive connective tissue disorder (joint dislocations, lax skin) associated with neurological abnormalities (severe global developmental delay, choreoathetosis) without metabolic abnormalities in four affected children. A genome-screen performed under a hypothesis of homozygosity by descent for an ancestral mutation, identified a locus at 10q23 (Z = 3.63). One gene within the candidate interval, ALDH18A1, encoding Delta1-pyrroline-5-carboxylate synthase (P5CS), was considered a plausible disease gene since a missense mutation had previously been shown to cause progressive neurodegeneration, cataracts, skin laxity, joint dislocations and metabolic derangement in a consanguineous Algerian family. A missense mutation, 2350C>T, was identified in ALDH18A1, which predicts the substitution H784Y. H784 is invariant across all phyla and lies within a previously unrecognised, conserved C-terminal motif in P5CS. In an in vivo assay of flux through this metabolic pathway using dermal fibroblasts obtained from an affected individual, proline and ornithine biosynthetic activity of P5CS was not affected by the H784Y substitution. These data suggest that P5CS may possess additional uncharacterised functions that affect connective tissue and central nervous system function.

  16. Biallelic truncating mutations in FMN2, encoding the actin-regulatory protein Formin 2, cause nonsyndromic autosomal-recessive intellectual disability.

    PubMed

    Law, Rosalind; Dixon-Salazar, Tracy; Jerber, Julie; Cai, Na; Abbasi, Ansar A; Zaki, Maha S; Mittal, Kirti; Gabriel, Stacey B; Rafiq, Muhammad Arshad; Khan, Valeed; Nguyen, Maria; Ali, Ghazanfar; Copeland, Brett; Scott, Eric; Vasli, Nasim; Mikhailov, Anna; Khan, Muhammad Nasim; Andrade, Danielle M; Ayaz, Muhammad; Ansar, Muhammad; Ayub, Muhammad; Vincent, John B; Gleeson, Joseph G

    2014-12-01

    Dendritic spines represent the major site of neuronal activity in the brain; they serve as the receiving point for neurotransmitters and undergo rapid activity-dependent morphological changes that correlate with learning and memory. Using a combination of homozygosity mapping and next-generation sequencing in two consanguineous families affected by nonsyndromic autosomal-recessive intellectual disability, we identified truncating mutations in formin 2 (FMN2), encoding a protein that belongs to the formin family of actin cytoskeleton nucleation factors and is highly expressed in the maturing brain. We found that FMN2 localizes to punctae along dendrites and that germline inactivation of mouse Fmn2 resulted in animals with decreased spine density; such mice were previously demonstrated to have a conditioned fear-learning defect. Furthermore, patient neural cells derived from induced pluripotent stem cells showed correlated decreased synaptic density. Thus, FMN2 mutations link intellectual disability either directly or indirectly to the regulation of actin-mediated synaptic spine density.

  17. A new locus for autosomal recessive non-syndromic mental retardation maps to 1p21.1-p13.3.

    PubMed

    Uyguner, O; Kayserili, H; Li, Y; Karaman, B; Nürnberg, G; Hennies, Hc; Becker, C; Nürnberg, P; Başaran, S; Apak, M Y; Wollnik, B

    2007-03-01

    Autosomal recessive inheritance of non-syndromic mental retardation (ARNSMR) may account for approximately 25% of all patients with non-specific mental retardation (NSMR). Although many X-linked genes have been identified as a cause of NSMR, only three autosomal genes are known to cause ARNSMR. We present here a large consanguineous Turkish family with four mentally retarded individuals from different branches of the family. Clinical tests showed cognitive impairment but no neurological, skeletal, and biochemical involvements. Genome-wide mapping using Human Mapping 10K Array showed a single positive locus with a parametric LOD score of 4.92 in a region on chromosome 1p21.1-p13.3. Further analyses using polymorphic microsatellite markers defined a 6.6-Mb critical region containing approximately 130 known genes. This locus is the fourth one linked to ARNSMR.

  18. Semiconductor devices having a recessed electrode structure

    DOEpatents

    Palacios, Tomas Apostol; Lu, Bin; Matioli, Elison de Nazareth

    2015-05-26

    An electrode structure is described in which conductive regions are recessed into a semiconductor region. Trenches may be formed in a semiconductor region, such that conductive regions can be formed in the trenches. The electrode structure may be used in semiconductor devices such as field effect transistors or diodes. Nitride-based power semiconductor devices are described including such an electrode structure, which can reduce leakage current and otherwise improve performance.

  19. Recession trims third-quarter building costs

    SciTech Connect

    Morgan, J.M.

    1983-05-09

    The composite cost index for building oil pipelines during the third quarter of 1982 showed a decrease of 0.96%. This decrease was due to a steady drop in the rate of inflation for most pipeline construction materials during the first 9 months of the year. The major thrust behind the pipeline materials decline was a sharp 5.3% drop in the average price of steel line pipe. However, the pipeline construction recession has failed to deter escalating pipeline labor rates.

  20. Cutting Symmetrical Recesses In Soft Ceramic Tiles

    NASA Technical Reports Server (NTRS)

    Nesotas, Tony C.; Tyler, Brent

    1989-01-01

    Simple tool cuts hemispherical recesses in soft ceramic tiles. Designed to expose wires of thermocouples embedded in tiles without damaging leads. Creates neat, precise holes around wires. End mill includes axial hole to accommodate thermocouple wires embedded in material to be cut. Wires pass into hole without being bent or broken. Dimensions in inches. Used in place of such tools as dental picks, tweezers, spatulas, and putty knives.

  1. Etiology and occurrence of gingival recession - An epidemiological study

    PubMed Central

    Mythri, Sarpangala; Arunkumar, Suryanarayan Maiya; Hegde, Shashikanth; Rajesh, Shanker Kashyap; Munaz, Mohamed; Ashwin, Devasya

    2015-01-01

    Objectives: Gingival recession is the term used to characterize the apical shift of the marginal gingiva from its normal position on the crown of the tooth. It is frequently observed in adult subjects. The occurrence and severity of the gingival recession present considerable differences between populations. To prevent gingival recession from occurring, it is essential to detect the underlying etiology. The aim of the present study was to determine the occurrence of gingival recession and to identify the most common factor associated with the cause of gingival recession. Methods: A total of 710 subjects aged between 15 years to 60 years were selected. Data were collected by an interview with the help of a proforma and then the dental examination was carried out. The presence of gingival recession was recorded using Miller's classification of gingival recession. The Silness and Loe Plaque Index, Loe and Silness gingival index, community periodontal index were recorded. The data thus obtained were subjected to statistical analysis using Chi-square test and Student's unpaired t-test. Results: Of 710 subjects examined, 291 (40.98%) subjects exhibited gingival recession. The frequency of gingival recession was found to increase with age. High frequency of gingival recession was seen in males (60.5%) compared to females (39.5%). Gingival recession was commonly seen in mandibular incisors (43.0%). Miller's class I gingival recession was more commonly seen. The most common cause for gingival recession was dental plaque accumulation (44.1%) followed by faulty toothbrushing (42.7%). Conclusion: Approximately half of the subjects examined exhibited gingival recession. The etiology of gingival recession is multifactorial, and its appearance is always the result of more than one factor acting together. PMID:26941519

  2. Diencephalic-Mesencephalic Junction Dysplasia: A Novel Recessive Brain Malformation

    ERIC Educational Resources Information Center

    Zaki, Maha S.; Saleem, Sahar N.; Dobyns, William B.; Barkovich, A. James; Bartsch, Hauke; Dale, Anders M.; Ashtari, Manzar; Akizu, Naiara; Gleeson, Joseph G.; Grijalvo-Perez, Ana Maria

    2012-01-01

    We describe six cases from three unrelated consanguineous Egyptian families with a novel characteristic brain malformation at the level of the diencephalic-mesencephalic junction. Brain magnetic resonance imaging demonstrated a dysplasia of the diencephalic-mesencephalic junction with a characteristic "butterfly"-like contour of the midbrain on…

  3. 'I never faced up to being gay': sexual, religious and ethnic identities among British Indian and British Pakistani gay men.

    PubMed

    Jaspal, Rusi

    2012-01-01

    This paper presents the findings from a comparative qualitative study of British Indian and British Pakistani gay men, all of whom self-identified as members of their religious communities. Data were analysed using thematic analysis and identity process theory. Results suggest that the intersection between sexuality and religion is more relevant to British Pakistani participants, while the intersection between sexuality and ethnicity is more relevant to British Indian participants. For British Indian participants in particular, homosexuality seems to be socially problematic, posing potential obstacles for interpersonal and intergroup relations. Conversely, for British Pakistanis, homosexuality is both socially and psychologically problematic, affecting intrapsychic as well as interpersonal levels of human interdependence. Theoretical and practical implications are discussed.

  4. 'I never faced up to being gay': sexual, religious and ethnic identities among British Indian and British Pakistani gay men.

    PubMed

    Jaspal, Rusi

    2012-01-01

    This paper presents the findings from a comparative qualitative study of British Indian and British Pakistani gay men, all of whom self-identified as members of their religious communities. Data were analysed using thematic analysis and identity process theory. Results suggest that the intersection between sexuality and religion is more relevant to British Pakistani participants, while the intersection between sexuality and ethnicity is more relevant to British Indian participants. For British Indian participants in particular, homosexuality seems to be socially problematic, posing potential obstacles for interpersonal and intergroup relations. Conversely, for British Pakistanis, homosexuality is both socially and psychologically problematic, affecting intrapsychic as well as interpersonal levels of human interdependence. Theoretical and practical implications are discussed. PMID:22651130

  5. A new classification system for gingival and palatal recession.

    PubMed

    Kumar, Ashish; Masamatti, Sujata Surendra

    2013-03-01

    Various classifications have been proposed to classify gingival recession. Miller's classification of gingival recession is most widely followed. With a wide array of cases in daily clinical practice, it is often difficult to classify numerous gingival recession cases according to defined criteria of the present classification systems. To propose a new classification system that gives a comprehensive depiction of recession defect that can be used to include cases that cannot be classified according to present classifications. A separate classification system for palatal recessions (PR) is also proposed. This article outlines the limitations of present classification systems and also the inability to classify PR. A new comprehensive classification system is proposed to classify recession on the basis of the position of interdental papilla and buccal/lingual/palatal recessions. PMID:23869122

  6. What mainly controls recession flows in river basins?

    NASA Astrophysics Data System (ADS)

    Biswal, Basudev; Nagesh Kumar, D.

    2014-03-01

    The ubiquity of the power law relationship between dQ/dt and Q for recession periods (-dQ/dt=kQα,Q being discharge at the basin outlet at time t) clearly hints at the existence of a dominant recession flow process that is common to all real basins. It is commonly assumed that a basin, during recession events, functions as a single phreatic aquifer resting on a impermeable horizontal bed or the Dupuit-Boussinesq (DB) aquifer, and with time different aquifer geometric conditions arise that give different values of α and k. The recently proposed alternative model, geomorphological recession flow model, however, suggests that recession flows are controlled primarily by the dynamics of the active drainage network (ADN). In this study we use data for several basins and compare the above two contrasting recession flow models in order to understand which of the above two factors dominates during recession periods in steep basins. Particularly, we do the comparison by selecting three key recession flow properties: (1) power law exponent α, (2) dynamic dQ/dt-Q relationship (characterized by k) and (3) recession timescale (time period for which a recession event lasts). Our observations suggest that neither drainage from phreatic aquifers nor evapotranspiration significantly controls recession flows. Results show that the value of α and recession timescale are not modeled well by DB aquifer model. However, the above mentioned three recession curve properties can be captured satisfactorily by considering the dynamics of the ADN as described by geomorphological recession flow model, possibly indicating that the ADN represents not just phreatic aquifers but the organization of various sub-surface storage systems within the basin.

  7. Distribution of HLA-DQA1 alleles in Arab and Pakistani individuals from Dubai, United Arab Emirates.

    PubMed

    Tahir, M A; al Khayat, A Q; al Shamali, F; Budowle, B; Novick, G E

    1997-03-14

    PCR-based typing of the HLA-DQA1 locus, using allele specific oligonucleotide (ASO) probes and reverse dot blot methodology was used to determine allelic distributions and construct a database for Arab and Pakistani individuals living in Dubai. Genotype and allelic frequencies were calculated, and the data were tested for departures from Hardy-Weinberg (HWE) equilibrium. The most frequent HLA-DQA1 alleles among Dubaian Arabs are DQA1 4 and 1.2. Among Pakistanis, the most frequent allele is also DQA1 4. No significant deviations from HWE were detected.

  8. Dietary patterns of Pakistani adults and their associations with sociodemographic, anthropometric and life-style factors.

    PubMed

    Safdar, Nilofer F; Bertone-Johnson, Elizabeth; Cordeiro, Lorraine; Jafar, Tazeen H; Cohen, Nancy L

    2013-01-01

    Dietary pattern analysis is an epidemiological method designed to consider the complexity of food preferences and diet patterns of populations. Few studies from South Asia have used this methodology to describe population food intake. Our objective was to identify dietary patterns and understand their associations with sociodemographic, anthropometric and life-style factors among low-income Pakistani urban adults. Dietary information was collected by a thirty-three-item FFQ and dietary patterns were derived by principal component analyses in 5491 subjects enrolled in the Control of Blood Pressure and Risk Attenuation (COBRA) study. Three dietary patterns were identified: a fat and sweet pattern characterised by fried snacks/foods, desserts, organ meats, bakery products, Pakistani bread and food purchased from outside the home; a fruit and vegetable pattern including fruits, juices, raw and cooked vegetables, lean meat and low-fat milk; and a seafood and yogurt pattern identified by prawns, fish, potatoes and yogurt. The fat and sweet pattern scores were low among older subjects, those with high BMI and waist circumference but high among females and physically active participants. The fruit and vegetable pattern was associated with younger age, high BMI, education and non-tobacco use. The seafood and yogurt pattern was associated with high BMI, increased physical activity and non-tobacco use. In conclusion, distinct dietary patterns exist for the Pakistani population that may be related to some of the population characteristics and thus may have importance in suggesting dietary and life-style interventions in the prevention of chronic diseases. PMID:25191598

  9. Perceptions of the causes of childhood disability among Pakistani families living in the UK.

    PubMed

    Croot, E J; Grant, G; Cooper, C L; Mathers, N

    2008-12-01

    It has been well documented that South Asian families caring for a child with a disability experience discrimination and disadvantage in accessing health and social care services. This gives increasing cause for concern as the number of South Asian people with severe learning impairments in the UK continues to rise. Mainstream services are ill-equipped to provide individual services to parents who choose to define and address disability differently, and whose concerns and solutions may differ from the majority population, despite the fact that these parents possess many strengths and may present alternative ways of addressing their needs. This study aimed to provide a detailed account of the ways that Pakistani parents living in a northern city in the UK and caring for a child with a disability, account for and understand their child's disability. Sixteen in-depth interviews were carried out between October 2002 and July 2003, with Pakistani parents and one grandparent of children with a disability. All final transcripts were in English, and a thematic analysis was undertaken. Results include a detailed account of parents' understanding of the causes of their child's disability. All parents made reference to theological explanations as to why they had a child with a disability; however, most parents also gave biomedical or other explanations. The relationship between theological and biomedical explanations was explored along with the consequences of the different beliefs for individuals and families. Parents also spoke vividly about the impact of negative and stigmatizing beliefs about causes of disability which they felt were prevalent in the Pakistani community, and they used a biomedical discourse to refute these ideas. The authors suggest that knowledge of individual and family beliefs, and awareness of the impact of these beliefs, can provide a valuable conceptual lens for health and social care practitioners to use when working in family-centred, culturally

  10. Association analysis of GWAS and candidate gene loci in a Pakistani population with psoriasis.

    PubMed

    Munir, Saeeda; ber Rahman, Simeen; Rehman, Sadia; Saba, Nusrat; Ahmad, Wasim; Nilsson, Staffan; Mazhar, Kehkashan; Naluai, Åsa Torinsson

    2015-03-01

    Psoriasis is a common inflammatory and hyper proliferative condition of the skin and a serious chronic systemic autoimmune disease. We undertook an association study to investigate the genetic etiology of psoriasis in a Pakistani population by genotyping single-nucleotide polymorphisms (SNPs) previously reported to be associated in genome-wide association (GWAS) or in candidate gene studies of psoriasis. Fifty seven single-nucleotide polymorphisms (SNPs) from 42 loci were genotyped in 533 psoriasis patients and 373 controls. Our results showed genome wide significant association of the MHC region (rs1265181 being the most significant from five SNPs used with overall OR=3.38; p=2.97E-18), as well as nominally significant associations at ten other loci (p<0.05) in the Pakistani population (LCE3B, REL, IL13/IL4, TNIP1, IL12B, TRAF3IP2, ZC3H12C, NOS2 and RNF114 from GWAS and PRR9 from a previous candidate gene study). Overall, only nine SNPs out of the 42 GWAS loci, displayed an odds ratio in the opposite allelic direction and only three did not reach similar odds ratio within 95% confidence interval as previously reported (SLC45A1/TNFRSF9, ELMO1 and IL28RA). This indicates similar genetic risk factors and molecular mechanisms behind disease in Pakistani psoriasis patients as in other populations. In addition, we show that the MHC and TNIP1 regions are significantly different in patients with psoriasis onset before the age of 40 (type I) compared to after 40 years of age (type II). MHC being associated mainly with type I while TNIP1 with type II patients.

  11. Dietary patterns of Pakistani adults and their associations with sociodemographic, anthropometric and life-style factors.

    PubMed

    Safdar, Nilofer F; Bertone-Johnson, Elizabeth; Cordeiro, Lorraine; Jafar, Tazeen H; Cohen, Nancy L

    2013-01-01

    Dietary pattern analysis is an epidemiological method designed to consider the complexity of food preferences and diet patterns of populations. Few studies from South Asia have used this methodology to describe population food intake. Our objective was to identify dietary patterns and understand their associations with sociodemographic, anthropometric and life-style factors among low-income Pakistani urban adults. Dietary information was collected by a thirty-three-item FFQ and dietary patterns were derived by principal component analyses in 5491 subjects enrolled in the Control of Blood Pressure and Risk Attenuation (COBRA) study. Three dietary patterns were identified: a fat and sweet pattern characterised by fried snacks/foods, desserts, organ meats, bakery products, Pakistani bread and food purchased from outside the home; a fruit and vegetable pattern including fruits, juices, raw and cooked vegetables, lean meat and low-fat milk; and a seafood and yogurt pattern identified by prawns, fish, potatoes and yogurt. The fat and sweet pattern scores were low among older subjects, those with high BMI and waist circumference but high among females and physically active participants. The fruit and vegetable pattern was associated with younger age, high BMI, education and non-tobacco use. The seafood and yogurt pattern was associated with high BMI, increased physical activity and non-tobacco use. In conclusion, distinct dietary patterns exist for the Pakistani population that may be related to some of the population characteristics and thus may have importance in suggesting dietary and life-style interventions in the prevention of chronic diseases.

  12. Recurrent exercise-induced acute renal failure in a young Pakistani man with severe renal hypouricemia and SLC2A9 compound heterozygosity

    PubMed Central

    2014-01-01

    Background Familial renal hypouricemia (RHUC) is a hereditary disease characterized by hypouricemia, high renal fractional excretion of uric acid (FE-UA) and can be complicated by acute kidney failure and nephrolithiasis. Loss-of-function mutations in the SLC22A12 gene cause renal hypouricemia type 1 (RHUC1), whereas renal hypouricemia type 2 (RHUC2) is caused by mutations in the SLC2A9 gene. Case presentation We describe a 24-year-old Pakistani man who was admitted twice to our hospital for severe exercise-induced acute renal failure (EIARF), abdominal pain and fever; he had very low serum UA levels (0.2 mg/dl the first time and 0.09 mg/dl the second time) and high FE-UA (200% and 732% respectively), suggestive of RHUC. Mutational analyses of both urate transporters revealed a new compound heterozygosity for two distinct missense mutations in the SLC2A9 gene: p.Arg380Trp, already identified in heterozygosity, and p.Gly216Arg, previously found in homozygosity or compound heterozygosity in some RHUC2 patients. Compared with previously reported patients harbouring these mutations, our proband showed the highest FE-UA levels, suggesting that the combination of p.Arg380Trp and p.Gly216Arg mutations most severely affects the renal handling of UA. Conclusions The clinical and molecular findings from this patient and a review of the literature provide new insights into the genotype-phenotype correlation of this disorder, supporting the evidence of an autosomal recessive inheritance pattern for RHUC2. Further investigations into the functional properties of GLUT9, URAT1 and other urate transporters are required to assess their potential research and clinical implications. PMID:24397858

  13. The politics of combating the organ trade: lessons from the Israeli and Pakistani experience.

    PubMed

    Efrat, A

    2013-07-01

    Israel and Pakistan--two major participants in the global organ trade--enacted legislative prohibitions on the trade at roughly the same time. The article highlights three influences that brought about this change of policy in both countries: advocacy by local physicians coupled with media coverage and reinforced by the international medical community. The analysis also explains why the two countries have differed with respect to the enforcement of the organ-trade prohibition. The insights from the Israeli and Pakistani cases will be of use for the transplant community's efforts against organ trafficking. PMID:23675678

  14. Detection of filaggrin gene mutation (2282del4) in Pakistani Ichthyosis vulgaris families.

    PubMed

    Naz, Naghma; Samdani, Azam Jah

    2011-06-01

    The aim of this study was to detect an 811 bp filaggrin (FLG) gene fragment known to carry a mutation 2282del4 which causes ichthyosis vulgaris. Seven clinically examined ichthyosis vulgaris families were included in this study. An 811 bp FLG gene fragment was targeted in the genomic DNA of all the members of the seven families by PCR amplification using known primers RPT1P7 and RPT2P1. Successful amplification of an 811 bp FLG gene fragment in all the families suggested the possible role of the 2282del4 mutation in causing ichthyosis vulgaris in Pakistani population.

  15. The politics of combating the organ trade: lessons from the Israeli and Pakistani experience.

    PubMed

    Efrat, A

    2013-07-01

    Israel and Pakistan--two major participants in the global organ trade--enacted legislative prohibitions on the trade at roughly the same time. The article highlights three influences that brought about this change of policy in both countries: advocacy by local physicians coupled with media coverage and reinforced by the international medical community. The analysis also explains why the two countries have differed with respect to the enforcement of the organ-trade prohibition. The insights from the Israeli and Pakistani cases will be of use for the transplant community's efforts against organ trafficking.

  16. Why the offline are offline: a survey of internet use by educated Pakistani adults.

    PubMed

    Shafique, Farzana; Mahmood, Khalid

    2009-06-01

    The study reported here explored the reasons for the relatively limited use of the Internet among educated Pakistani adults. A fairly large sample of Internet nonusers from different cities of the Punjab Province with at least secondary school education participated in a survey. Some graduate students and cyber café owners were also interviewed. The results of this study are reported in the main body of this paper, indicating that a variety of cultural, educational, and economic factors are responsible for this state of affairs.

  17. [Consanguineous marriage and morbi-mortality, short literature review based on an exceptional association: Usher syndrome and Von Recklinghausen neurofibromatosis].

    PubMed

    Atipo-Tsiba, Pépin-Williams

    2016-01-01

    Usher syndrome is defined by the association of a progressive or non-progressive congenital sensorineural hearing loss with variable severity and a gradually blinding pigmentary retinopathy. Von Recklinghausen neurofibromatosis or Neurofibromatosis type 1 is the major clinically form of neurofibromatosis which occurs in approximately 90% of cases. Both types of disease are genetic in origin with very low prevalence. The probability of co-occurrence of these diseases in a single individual is exceptional. Inbreeding, as well as all genetic diseases, increases quite significantly the probability of their occurrence. Consanguineous marriages are still widespread in Maghreb and in some regions of the western African. This observation reports an exceptional case of this association in a 40-year-old man of Mauritanian origin born from a consanguineous union.

  18. ABCA12 mutations and autosomal recessive congenital ichthyosis: a review of genotype/phenotype correlations and of pathogenetic concepts.

    PubMed

    Akiyama, Masashi

    2010-10-01

    Mutations in ABCA12 have been described in autosomal recessive congenital ichthyoses (ARCI) including harlequin ichthyosis (HI), congenital ichthyosiform erythroderma (CIE), and lamellar ichthyosis (LI). HI shows the most severe phenotype. CIE and LI are clinically characterized by fine, whitish scales on a background of erythematous skin, and large, thick, dark scales over the entire body without serious background erythroderma, respectively. To date, a total of 56 ABCA12 mutations have been reported in 66 ARCI families including 48 HI, 10 LI, and 8 CIE families of African, European, Pakistani/Indian, and Japanese origin (online database: http://www.derm-hokudai.jp/ABCA12/). A total of 62.5% of reported ABCA12 mutations are expected to lead to truncated proteins. Most mutations in HI are truncation mutations and homozygous or compound heterozygous truncation mutations always results in HI phenotype. In CIE families, at least one mutation on each allele is typically a missense mutation. Combinations of missense mutations in the first ATP-binding cassette of ABCA12 underlie the LI phenotype. ABCA12 is a keratinocyte lipid transporter associated with lipid transport in lamellar granules, and loss of ABCA12 function leads to a defective lipid barrier in the stratum corneum, resulting in an ichthyotic phenotype. Recent work using mouse models confirmed ABCA12 roles in skin barrier formation.

  19. CFLs in Recessed Downlights: Technical Challenges

    SciTech Connect

    Ledbetter, Marc R.; McCullough, Jeffrey J.; Dillon, Heather E.; Sandahl, Linda J.; Gordon, Kelly L.

    2005-05-09

    Recessed downlights are the most popular residential lighting fixture in the United States representing about 12 percent of installed residential lighting fixtures and 15 percent of total lighting energy use nationwide. We estimate 400 million recessed downlights are currently installed in American homes, almost all using incandescent light sources. In the year 2000, only 0.44 percent of recessed cans sold were hard-wired for using pin-based CFLs. Recessed downlights consume energy in three ways. First, their incandescent light sources use energy directly, drawing 65 to 150 watts. Second, they consume energy indirectly by adding heat from their light sources to air-conditioning loads. Third, since most are not airtight, they also consume energy indirectly by allowing conditioned air to escape into unconditioned areas above the downlights, such as attics. PNNL calculated potential energy savings and found that if a 65W incandescent non-airtight downlight is replaced with a 26W CFL ICAT downlight operated at 3 hrs per day savings will be 126 kWh/yr. Early reflector CFLs have had high return rates primarily because of failure due to thermal related stress. A PNNL laboratory test of ten commercially available R-CFLs selected from retail store shelves showed almost all operated above their manufacturer rated maximum operating temperatures when they were installed and tested in ICAT downlights in a simulated insulated ceiling apparatus. DOE asked PNNL to investigate the development and introduction of both pin-based and screw-based CFLs for use in ICAT fixtures. PNNL invited manufacturers to submit lamps to a procurement program. PNNL conducted short- and long-term thermal testing of the lamps to measure performance parameters affected by elevated temperatures. 8 out of 10 R-CFLs (secrew-based lamps) failed the long-tem testing. Five out of nine CFL-ICAT (pin-based CFL) fixtures passed the long-term test, surviving a full year of operation in a simulated insulated

  20. The Diagnostic Utility of Single Long Contiguous Stretches of Homozygosity in Patients without Parental Consanguinity

    PubMed Central

    Pajusalu, Sander; Žilina, Olga; Yakoreva, Maria; Tammur, Pille; Kuuse, Kati; Mölter-Väär, Triin; Nõukas, Margit; Reimand, Tiia; Õunap, Katrin

    2015-01-01

    We present data from our clinical department's experience with chromosomal microarray analysis (CMA) regarding the diagnostic utility of 1 or 2 long contiguous stretches of homozygosity (LCSHs) in an outbred population. The study group consisted of 2,110 consecutive patients from 2011 to 2014 for whom CMA was performed. The minimum cut-off size for defining a homozygous stretch was 5 Mb. To focus on cases with no parental consanguinity, we further studied only patients in whom the total length of homozygous stretches did not exceed 28 Mb or 1% of the autosomal genome length. We identified 6 chromosomal regions where homozygous stretches appeared in at least 3 patients and excluded these from further analysis. In 2 out of 120 patients with an isolated finding of 1 or 2 non-recurrent LCSHs, a plausible candidate gene associated with their phenotype was identified within the homozygous stretch. In both of these cases, a pathogenic mutation was detected, leading to diagnoses of pyruvate kinase deficiency and Marinesco-Sjögren syndrome. To clarify whether previously found homozygous stretches could be important for the interpretation of genome-wide sequencing data, we report 7 cases in which homozygous stretches not encompassing a clinically associated gene were first found on CMA, followed by the diagnostic whole-exome sequencing. The diagnostic utility of single LCSHs, unlikely to be caused by uniparental disomy, is discussed in detail. PMID:26733775

  1. Consanguineous 3-methylcrotonyl-CoA carboxylase deficiency: early-onset necrotizing encephalopathy with lethal outcome.

    PubMed

    Baykal, T; Gokcay, G Huner; Ince, Z; Dantas, M F; Fowler, B; Baumgartner, M R; Demir, F; Can, G; Demirkol, M

    2005-01-01

    A patient with a severe neonatal variant of 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is reported. The first child of healthy consanguineous Turkish parents presented on the second day of life with dehydration, cyanosis, no sucking, generalized muscular hypotonia, encephalopathy, respiratory depression requiring mechanic ventilation, macrocephaly, severe acidosis and hypoglycaemia. Elevated C5-OH-carnitine in dried blood spot by tandem MS and elevated urinary excretion of 3-hydroxyisovaleric acid and 3-methylcrotonylglycine suggested MCC deficiency, confirmed by enzyme analysis in cultured fibroblasts. Cerebral ultrasonography and cranial CT findings revealed progressive changes such as disseminated encephalomalacia, cystic changes, ventricular dilatation and cerebral atrophy. Treatment with high-dose biotin and protein-restricted diet was ineffective and the patient died at the age of 33 days with progressive neurological deterioration. Mutation analysis revealed a homozygous mutation in the splice acceptor site of intron 15 in the MCC beta-subunit. Early-onset severe necrotizing encephalopathy should be included in the differential diagnosis of isolated MCC deficiency.

  2. Q192R paraoxonase1 polymorphism is a risk factor for cataract in Pakistani population.

    PubMed

    Baig, Amena; Zohaib, Muhammad; Rehman, Ata-ur; Zarina, Shamshad

    2016-05-01

    Cataract, the lens opacity, is among major causes of blindness in Pakistani population. In recent past, oxidative stress is suggested to play crucial role in loss of transparency. Along with other antioxidants, Paraoxonase 1 (PON1) has also shown decreased activity in patients suffering from cataract. The aim of current study was to examine the possible association of PON polymorphism with predisposition of cataract formation in local population. The study was conducted on 51 cataract patients and 50 control subjects considering all ethical issues. DNA was extracted from whole blood and PON1 polymorphism was identified using tetra primer ARMS-PCR method for both positions L55M and Q192R. Tetra primer ARMS-PCR results revealed that association between L55M polymorphism and cataract was insignificant while 192R genotype PON1 frequency was higher among the people suffering from cataract (78.4%) as compared to control subjects (56%), (odds ratio=2.857, confidence interval=1.197-6.820). Hence, R allele is likely to be a risk factor for cataract with allele frequency (82.3%) and (odds ratio=4.552, confidence interval=1.716-12.073, p-value=0.002). PON1 Q192R polymorphism is likely to be a risk factor for cataract development in Pakistani population while PON1 L55M was not found to be associated with cataract. PMID:27166546

  3. Q192R paraoxonase1 polymorphism is a risk factor for cataract in Pakistani population.

    PubMed

    Baig, Amena; Zohaib, Muhammad; Rehman, Ata-ur; Zarina, Shamshad

    2016-05-01

    Cataract, the lens opacity, is among major causes of blindness in Pakistani population. In recent past, oxidative stress is suggested to play crucial role in loss of transparency. Along with other antioxidants, Paraoxonase 1 (PON1) has also shown decreased activity in patients suffering from cataract. The aim of current study was to examine the possible association of PON polymorphism with predisposition of cataract formation in local population. The study was conducted on 51 cataract patients and 50 control subjects considering all ethical issues. DNA was extracted from whole blood and PON1 polymorphism was identified using tetra primer ARMS-PCR method for both positions L55M and Q192R. Tetra primer ARMS-PCR results revealed that association between L55M polymorphism and cataract was insignificant while 192R genotype PON1 frequency was higher among the people suffering from cataract (78.4%) as compared to control subjects (56%), (odds ratio=2.857, confidence interval=1.197-6.820). Hence, R allele is likely to be a risk factor for cataract with allele frequency (82.3%) and (odds ratio=4.552, confidence interval=1.716-12.073, p-value=0.002). PON1 Q192R polymorphism is likely to be a risk factor for cataract development in Pakistani population while PON1 L55M was not found to be associated with cataract.

  4. Major dietary patterns and risk of acute myocardial infarction in young, urban Pakistani population

    PubMed Central

    Iqbal, Romaina; Iqbal, Saleem Perwaiz; Yakub, Mohsin; Tareen, Asal Khan; Iqbal, Mohammad Perwaiz

    2015-01-01

    Objective: To investigate the role of dietary intake in the development of premature acute myocardial infarction (AMI) in a hospital-based Pakistani population in Karachi. Methods: In a case control study, 203 consecutive patients (146 males and 57 females) with their first AMI and age below 45 years were enrolled with informed consent. Similarly, 205 gender and age matched (within 3 years) healthy adults were also included as controls. Dietary intake of both cases and controls was assessed by using a simple 14-item food frequency questionnaire. Using factor analysis, 3 major dietary patterns- prudent dietary pattern, combination dietary pattern and western dietary pattern were identified. Fasting plasma/serum of both cases and controls were analyzed for homocysteine, folate, vitamin B12, blood Pb, ferritin, cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. ANOVA and conditional logistic regression were used to predict the association of dietary patterns with AMI. Results: Consumption of prudent diet, characterized by high consumption of legumes, vegetables, wheat, chicken and fruits, is protective against the risk of premature AMI. Moderate to high consumption of combination diet, characterized by high intake of eggs, fish, fruits, juices and coffee was associated with decreased risk of AMI. No association was observed between western diet, characterized by high intake of meat, fish and tea with milk and risk of AMI. Conclusions: Consumption of a prudent dietary pattern and a combination dietary pattern is protective against the risk of AMI in a Pakistani population. PMID:26649016

  5. Continuing bonds in bereaved Pakistani Muslims: effects of culture and religion.

    PubMed

    Suhail, Kausar; Jamil, Naila; Oyebode, Jan; Ajmal, Mohammad Asir

    2011-01-01

    This study explores the bereavement process and continuing bond in Pakistani Muslims with the focus on how culture and religion influence these processes. Ten participants were interviewed and their transcribed interviews were analyzed using a grounded theory approach. Three main domains were identified from the narratives expressed by the participants: death and the process of grieving, continuing the link with the deceased, and influencing agents. The findings indicated that Pakistani Muslims maintained their link with the deceased through cultural and religious rituals, such as performing prayers, reciting holy verses, talking and dreaming about the deceased, doing charity, visiting graves, and arranging communal gatherings. The prime purpose of many of these practices was the forgiveness of the deceased. Grief reactions seemed to be determined by the nature of death, prior relationships with the deceased, reaction of society and gender of the bereaved. Religion provided a strong basis for coping and adjustment of the bereaved, through rationalizing and accepting the death. This study has important implications for counselors and family therapists who can use religious affliations to reduce the impact of loss and complicated bereavement.

  6. Return migration and occupational change: the case of Pakistani migrants returned from the Middle East.

    PubMed

    Arif, G M; Irfan, M

    1997-01-01

    This paper reports on the factors affecting occupational composition of Pakistani workers upon their return from Middle East employment locations as determined by using the 1986 ILO/ARTEP Survey of Return Migrant Households. Three issues related to post-migration occupation change of return migrants were explored: 1) the comparison of occupational composition in the pre-migration phase with the composition during migration; 2) the direction of occupational change; and 3) the factors affecting these changes after return. 44% of the total employed in the ILO sample changed their pre-migration occupations upon return from employment in production or service jobs to smallbusinessrelated employment; the highest level of occupational change was observed in nonirrigated areas. Occupational change was strongly related to migrants' duration of stay in the Middle East, their ages upon returning, and their level of educational attainment. Occupational mobility experienced by the returnees was mainly towards the business sectora direction approved by the Pakistan Government. The preference of the returnees to work independently might have enabled them to earn sufficient money to maintain their higher standard of living into the period following return migration. It is concluded that in order to achieve stability in the businesses established by the returnees, the Overseas Pakistanis' Foundation should provide services, including project-oriented training courses and loan plans, that will aid the returnees in managing their small businesses.

  7. Intimate partner violence against women and its related immigration stressors in Pakistani immigrant families in Germany

    PubMed Central

    2012-01-01

    This paper addresses the issue of intimate partner violence against women and its related immigration stressors in Pakistani immigrant families in Germany. Drawing on 32 in-depth interviews with Pakistani women in three cities in Germany, we found that psychological violence was the commonly reported violence among the study participants. The data showed that the process of immigration exacerbated tensions between spouses because of various immigration stressors such as threats to cultural identity, children’s socialization, and social isolation. In order to cope with the stressful spousal relations, women applied various indigenous strategies, but avoided seeking help from the host country’s formal care-providing institutions. This study also debunks some stereotypes and popular media clichés about the “victimhood of women from conservative developing countries” and provides an understanding of the issue of intimate partner violence within an immigration context. Further research with a larger sample will be helpful to understand immigration-induced stress and intimate partner violence in immigrant families. PMID:23984223

  8. Urban and rural comparison of vitamin D status in Pakistani pregnant women and neonates.

    PubMed

    Anwar, S; Iqbal, M P; Azam, I; Habib, A; Bhutta, S; Soofi, S B; Bhutta, Z A

    2016-01-01

    We undertook a cross-sectional study in rural Jehlum and urban Karachi to evaluate the prevalence of vitamin D deficiency in Pakistani pregnant women and neonates and to assess any association of serum 25(OH) vitamin D [25(OH)D] concentration with vitamin D binding protein (Gc) genotypes. Altogether, 390 women and 266 neonates were recruited from urban and rural sites, respectively. Serum 25(OH)D was measured by an immunoassay, while Gc genotypes were identified using polymerase chain reaction followed by restriction fragment length polymorphism or PCR-RFLP. One-way analysis of variance or ANOVA and linear regression were used for statistical analysis. In urban Karachi, 99.5% of women and 97.3% of neonates were vitamin D deficient (< 50 nmol/L), while 89% of women and 82% of neonates were deficient in rural Jehlum. Gc genotypes were not associated with serum 25(OH)D concentrations in both women and their neonates. We conclude that vitamin D deficiency is highly prevalent in Pakistani women and their neonates, and Gc genotypes are not associated with serum 25(OH)D concentrations.

  9. Molecular phylogeny of Pakistani riverine buffalo based on genetic variability of mitochondrial cytochrome b gene.

    PubMed

    Saif, Rashid; Wasim, Muhammad; Babar, Masroor Ellahi

    2012-10-01

    Mitochondrial cytochrome b gene is considered to be one of the best markers for breed characterization as well as studying the ancestry in the vertebrates due to its exclusive maternal inheritance. DNA fingerprinting by single nucleotide polymorphism is most reliable and widely used molecular technique in modern forensics and is being considered in this study. Partial sequencing of 1,061 bp of aforementioned gene from 14580 to 15643 was conducted in two famous Pakistani buffalo breeds named Nili-Ravi and Kundi. In which we explore seven haplotypes within earlier and none in the latter breed. Nili-Ravi is polymorphic at four codons of this gene, and the protein translation is also different from the reference sample while monomorphic at three codons with no amino acid replacement. Haplotypes frequency distribution of these four haplotypes named NR3, NR4, NR5, NR7 revealed that the prevalence of each haplotype is 0.04 % in the Pakistani buffalo population of this Nili-Ravi breed while complete homoplasmy was observed in the Kundi breed population. Nili-Ravi breed of buffalo is genetically more variable than the Kundi breed as far as the gene in subject is concerned. It means later breed has spent more time to propagate its wild type haplotype which make this breed more ancestral as compare to Nili-Ravi. Secondly both breeds share their common ancestors with regional water buffalo rather than the swamp one.

  10. Characterization and screening of bacteria from rhizosphere of maize grown in Indonesian and Pakistani soils.

    PubMed

    Naureen, Zakira; Yasmin, Sumera; Hameed, Sohail; Malik, K A; Hafeez, Fauzia Y

    2005-01-01

    Thirty rhizobacteria isolated from maize grown in Pakistani and Indonesian soils were evaluated for their morphological characteristics, nitrogen fixation, P-solubilization, indole acetic acid (IAA) and siderophores production. Nitrogenase activity was detected in nineteen isolates ranging from 21.8-3624 n moles C2H4 produced/h/mg protein. Most of the isolates produced IAA, ten were capable of siderophore production while four were P-solubilizers. Ultrastructural studies of Pseudomonas sp. F14 indicated characteristic rhizospheric colonization within 48 h that was observed to change considerably with the passage of time from few bacteria to micro colonies. Random amplified polymorphic DNA (RAPD) analysis of 30 bacterial strains using 30 oligonucleotide primers resulted in considerable level of genetic diversity, with genetic distance ranging from 2-16%. Indonesian isolates were found to be more diverse as compared to Pakistani isolates. The characterization and screening of rhizobacteria of maize rhizosphere has helped in selection of isolates F7, LS-1, 3.1.1.C, F2, F3 and F13 as superior strains for use as bioinoculant. Moreover isolate F14 identified, as Pseudomonas fulgida by partial 16S rRNA sequence analysis is a novel strain regarding its tremendous potentials for inoculum production to enhance the yield of maize. PMID:16304707

  11. Autosomal recessive brachyolmia: early radiological findings.

    PubMed

    Handa, Atsuhiko; Tham, Emma; Wang, Zheng; Horemuzova, Eva; Grigelioniene, Giedre

    2016-11-01

    Brachyolmia (BO) is a heterogeneous group of skeletal dysplasias with skeletal changes limited to the spine or with minimal extraspinal features. BO is currently classified into types 1, 2, 3, and 4. BO types 1 and 4 are autosomal recessive conditions caused by PAPSS2 mutations, which may be merged together as an autosomal recessive BO (AR-BO). The clinical and radiological signs of AR-BO in late childhood have already been reported; however, the early manifestations and their age-dependent evolution have not been well documented. We report an affected boy with AR-BO, whose skeletal abnormalities were detected in utero and who was followed until 10 years of age. Prenatal ultrasound showed bowing of the legs. In infancy, radiographs showed moderate platyspondyly and dumbbell deformity of the tubular bones. Gradually, the platyspondyly became more pronounced, while the bowing of the legs and dumbbell deformities of the tubular bones diminished with age. In late childhood, the overall findings were consistent with known features of AR-BO. Genetic testing confirmed the diagnosis. Being aware of the initial skeletal changes may facilitate early diagnosis of PAPSS2-related skeletal dysplasias. PMID:27544198

  12. [Autosomal recessive ethnic diseases of Czech Gypsies].

    PubMed

    Seeman, P; Sisková, D

    2006-01-01

    Roma (Gypsy ethnic) form a genetically isolated ethnical group of the identical origin with the world population of 10 to 14 millions derived from a limited number of so-called founders. Majority (about 8 millions) of Roma ethnic live in Europe, namely at Balkan and in the southwest of Europe. Roma have specific hereditary diseases, namely those caused by recessive genetic mutations. The molecular-genetic mechanism has been recently elucidated and confirmed in several diseases of the Roma population. Owing to the significant proportion of Roma in the population, patients with those diseases are possible to meet also in the Czech Republic. However, the diagnostics of those diseases is frequently difficult and they are often under diagnosed or misdiagnosed. The article gives examples of autosomal recessive diseases, which can be confirmed at the DNA level which occur in Roma population of the Czech Republic: syndrome of congenital cataract, facial dysmorphism and demyelinating neuropathy, non-syndromic prelingual deafness with GJB2 gene impairment and the congenital myastenic syndrome. PMID:16921785

  13. Misregulation of mitotic chromosome segregation in a new type of autosomal recessive primary microcephaly.

    PubMed

    Marchal, Juan Alberto; Ghani, Mahdi; Schindler, Detlev; Gavvovidis, Ioannis; Winkler, Tina; Esquitino, Veronique; Sternberg, Nadine; Busche, Andreas; Krawitz, Peter; Hecht, Joachim; Robinson, Peter; Mundlos, Stephan; Graul-Neumann, Luitgard; Sperling, Karl; Trimborn, Marc; Neitzel, Heidemarie

    2011-09-01

    Primary autosomal recessive microcephaly (MCPH) is a congenital disorder characterized by a pronounced reduction of brain size and mental retardation. We present here a consanguineous Turkish family clinically diagnosed with MCPH and without linkage to any of the known loci (MCPH1-MCPH7). Autozygosity mapping identified a homozygous region of 15.8 Mb on chromosome 10q11.23-21.3, most likely representing a new locus for MCPH. Although we were unable to identify the underlying genetic defect after extensive molecular screening, we could delineate a possible molecular function in chromosome segregation by the characterization of mitosis in the patients' cells. Analyses of chromosome nondisjunction in T-lymphocytes and fibroblasts revealed a significantly elevated rate of nondisjunction in the patients' cells as compared to controls. Mitotic progression was further explored by immunofluorescence analyses of several chromosome and spindle associated proteins. We detected a remarkable alteration in the anaphase distribution of Aurora B and INCENP, which are key regulators of chromosome segregation. In particular, a fraction of both proteins remained abnormally loaded on chromosomes during anaphase in MCPH patients' cells while in cells of normal control subjects both proteins are completely transferred to the spindle midzone. We did not observe any other alterations regarding cell cycle progression, chromosome structure, or response to DNA damage. Our observations point towards a molecular role of the underlying gene product in the regulation of anaphase/telophase progression possibly through interaction with chromosomal passenger proteins. In addition, our findings represent further evidence for the proposed role of MCPH genes in the regulation of mitotic progression.

  14. Autosomal Recessive Retinitis Pigmentosa with Early Macular Affectation Caused by Premature Truncation in PROM1

    PubMed Central

    Permanyer, Jon; Navarro, Rafael; Friedman, James; Pomares, Esther; Castro-Navarro, Joaquín; Marfany, Gemma; Swaroop, Anand

    2010-01-01

    Purpose. To identify the genetic basis of a large consanguineous Spanish pedigree affected with autosomal recessive retinitis pigmentosa (arRP) with premature macular atrophy and myopia. Methods. After a high-throughput cosegregation gene chip was used to exclude all known RP and Leber congenital amaurosis (LCA) candidates, genome-wide screening and linkage analysis were performed. Direct mutational screening identified the pathogenic mutation, and primers were designed to obtain the RT-PCR products for isoform characterization. Results. Mutational analysis detected a novel homozygous PROM1 mutation, c.869delG in exon 8 cosegregating with the disease. This variant causes a frameshift that introduces a premature stop codon, producing truncation of approximately two-thirds of the protein. Analysis of PROM1 expression in the lymphocytes of patients, carriers, and control subjects revealed an aberrant transcript that is degraded by the nonsense-mediated decay pathway, suggesting that the disease is caused by the absence of the PROM1 protein. Three (s2, s11 and s12) of the seven alternatively spliced isoforms reported in humans, accounted for 98% of the transcripts in the retina. Given that these three contained exon 8, no PROM1 isoform is expected in the affected retinas. Conclusions. A remarkable clinical finding in the affected family is early macular atrophy with concentric spared areas. The authors propose that the hallmark of PROM1 truncating mutations is early and severe progressive degeneration of both rods and cones and highlight this gene as a candidate of choice to prioritize in the molecular genetic study of patients with noncanonical clinical peripheral and macular affectation. PMID:20042663

  15. An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls.

    PubMed

    Saba, Nusrat; Yusuf, Osman; Rehman, Sadia; Munir, Saeeda; Ahmad, Sheeraz; Mansoor, Atika; Raja, Ghazala K

    2016-09-01

    Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variable symptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a major role in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the role of ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects, including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism was genotyped using polymerase chain reaction (PCR). Chi-square, Fisher's exact and Hardy-Weinberg equilibrium tests were used to compare groups. Homozygous insertion genotype II (p less than 0.0001, OR=3.38) and insertion allele (I) was significantly more frequent in Pakistani asthmatics than in healthy controls (p=0.0007, OR=1.40). The ID genotype (p less than 0.0001, OR=0.43) and the deletion allele (D) were associated with protection of disease in Pakistani patients (p=0.0007, OR=0.71). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistani population. This marker may be an important indication in the molecular mechanism of asthma and can become a useful tool in risk assessment and help in designing strategy to combat disease.

  16. Influences of Religion and Culture on Continuing Bonds in a Sample of British Muslims of Pakistani Origin

    ERIC Educational Resources Information Center

    Hussein, Hanan; Oyebode, Jan R.

    2009-01-01

    This study considered the nature of continuing bonds with deceased relatives in a sample of Pakistani Muslims living in the United Kingdom. Ten participants were interviewed following a cultural psychology approach and transcripts were analyzed using grounded theory methodology. Dreaming, talking with others about the deceased, following the…

  17. Validation of molecular markers for resistance among Pakistani chickpea germplasm to races of Fusarium oxysporum f. sp. ciceris

    Technology Transfer Automated Retrieval System (TEKTRAN)

    DNA markers in chickpea have been identified against different races of Fusarium oxysporum f.sp. ciceris (Foc), but validation of these markers is essential for their effective use in resistant breeding. In view of this, different simple sequence repeats (SSR) markers were analysed in Pakistani ger...

  18. "Narrow-Minded and Oppressive" or a "Superior Culture"? Implications of Divergent Representations of Islam for Pakistani-American Youth

    ERIC Educational Resources Information Center

    Ghaffar-Kucher, Ameena

    2015-01-01

    Drawing on ethnographic data, this article examines the complex terrain that working-class Pakistani-American youth must negotiate in their daily lives. Specifically, the article illustrates how particular views of Islam and Americanization manifest in particular sites and within educational discourses, and the resulting dissonance that youth…

  19. An angiotensin I-converting enzyme insertion/deletion polymorphism is associated with Pakistani asthmatic cases and controls.

    PubMed

    Saba, Nusrat; Yusuf, Osman; Rehman, Sadia; Munir, Saeeda; Ahmad, Sheeraz; Mansoor, Atika; Raja, Ghazala K

    2016-09-01

    Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variable symptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a major role in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the role of ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects, including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism was genotyped using polymerase chain reaction (PCR). Chi-square, Fisher's exact and Hardy-Weinberg equilibrium tests were used to compare groups. Homozygous insertion genotype II (p less than 0.0001, OR=3.38) and insertion allele (I) was significantly more frequent in Pakistani asthmatics than in healthy controls (p=0.0007, OR=1.40). The ID genotype (p less than 0.0001, OR=0.43) and the deletion allele (D) were associated with protection of disease in Pakistani patients (p=0.0007, OR=0.71). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistani population. This marker may be an important indication in the molecular mechanism of asthma and can become a useful tool in risk assessment and help in designing strategy to combat disease. PMID:27581935

  20. A Transnational Community of Pakistani Muslim Women: Narratives of Rights, Honor, and Wisdom in a Women's Education Project

    ERIC Educational Resources Information Center

    Khurshid, Ayesha

    2012-01-01

    Using ethnographic data, this article explores how Muslim women teachers from low-income Pakistani communities employ the notion of "wisdom" to construct and perform their educated subjectivity in a transnational women's education project. Through Butler's performativity framework, I demonstrate how local and global discourses overlap to shape…

  1. Body size perceptions among Pakistani women in Norway participating in a controlled trial to prevent deterioration of glucose tolerance.

    PubMed

    Hussain, Aysha; Bjørge, Benedikte; Hjellset, Victoria T; Holmboe-Ottesen, Gerd; Wandel, Margareta

    2010-06-01

    South Asians are prone to diabetes type 2 and cardiovascular diseases, which can be prevented by a diet leading to weight reduction. Body size perceptions may influence compliance to dietary advice. The objective was to study body size perceptions among Pakistani immigrant women in Norway, enrolled in a controlled trial to prevent deterioration of glucose tolerance by focussing on diet and physical activity. Participants (n=198) were 25-62 years of age, 79.8% had BMI > 25 and mean BMI was 29.6. Data were collected by questionnaire interviews with Punjabi/Urdu speaking interviewers, and body weight and height were measured. This article is based on baseline data. Stunkard's Figure Rating Scale was used. The scale consists of nine figures, representing women with different body shapes, from very thin (1-2) to very obese (6-9). The women were asked which body size they thought would connote health and wealth. A significantly smaller body size was related to health (mean 2.9) than to wealth (mean 3.3), p<0.01, and both were smaller than their self-rated own body size (mean 5.7), p<0.01. The women perceived that Pakistanis in Norway prefer women to have a smaller body size (mean 3.4) than people in Pakistan (mean 4.5), but larger than Norwegians (mean 2.5). A discrepancy score was calculated between self-rated own body size and perceived body size preference among Pakistanis in Norway. BMI was positively associated, and level of education negatively associated, with the discrepancy score. The women related body size numbers to BMI similarly to what has been described for US women. In conclusion, body size preferences among Pakistani women in this study were within the range of normal weight. However, there was a large discrepancy between own self-rated body size and the perceived ideal for Pakistanis in Norway. PMID:20379892

  2. Novel mutations confirm that COL11A2 is responsible for autosomal recessive non-syndromic hearing loss DFNB53.

    PubMed

    Chakchouk, Imen; Grati, M'hamed; Bademci, Guney; Bensaid, Mariem; Ma, Qi; Chakroun, Amine; Foster, Joseph; Yan, Denise; Duman, Duygu; Diaz-Horta, Oscar; Ghorbel, Abdelmonem; Mittal, Rahul; Farooq, Amjad; Tekin, Mustafa; Masmoudi, Saber; Liu, Xue Zhong

    2015-08-01

    Hearing loss (HL) is a major public health issue. It is clinically and genetically heterogeneous.The identification of the causal mutation is important for early diagnosis, clinical follow-up, and genetic counseling. HL due to mutations in COL11A2, encoding collagen type XI alpha-2, can be non-syndromic autosomal-dominant or autosomal-recessive, and also syndromic as in Otospondylomegaepiphyseal Dysplasia, Stickler syndrome type III, and Weissenbacher-Zweymuller syndrome. However, thus far only one mutation co-segregating with autosomal recessive non-syndromic hearing loss (ARNSHL) in a single family has been reported. In this study, whole exome sequencing of two consanguineous families with ARNSHL from Tunisia and Turkey revealed two novel causative COL11A2 mutations, c.109G > T (p.Ala37Ser) and c.2662C > A (p.Pro888Thr). The variants identified co-segregated with deafness in both families. All homozygous individuals in those families had early onset profound hearing loss across all frequencies without syndromic findings. The variants are predicted to be damaging the protein function. The p.Pro888Thr mutation affects a -Gly-X-Y- triplet repeat motif. The novel p.Ala37Ser is the first missense mutation located in the NC4 domain of the COL11A2 protein. Structural model suggests that this mutation will likely obliterate, or at least partially compromise, the ability of NC4 domain to interact with its cognate ligands. In conclusion, we confirm that COL11A2 mutations cause ARNSHL and broaden the mutation spectrum that may shed new light on genotype-phenotype correlation for the associated phenotypes and clinical follow-up. PMID:25633957

  3. Novel mutations confirm that COL11A2 is responsible for autosomal recessive non-syndromic hearing loss DFNB53

    PubMed Central

    Chakchouk, Imen; Grati, M’hamed; Bademci, Guney; Bensaid, Mariem; Ma, Qi; Chakroun, Amine; Foster, Joseph; Yan, Denise; Duman, Duygu; Diaz-Horta, Oscar; Ghorbel, Abdelmonem; Mittal, Rahul; Farooq, Amjad; Tekin, Mustafa

    2015-01-01

    Hearing loss (HL) is a major public health issue. It is clinically and genetically heterogeneous. The identification of the causal mutation is important for early diagnosis, clinical follow-up, and genetic counseling. HL due to mutations in COL11A2, encoding collagen type XI alpha-2, can be non-syndromic autosomal-dominant or autosomal-recessive, and also syndromic as in Otospondylomegaepiphyseal Dysplasia, Stickler syndrome type III, and Weissenbacher–Zweymuller syndrome. However, thus far only one mutation co-segregating with autosomal recessive non-syndromic hearing loss (ARNSHL) in a single family has been reported. In this study, whole exome sequencing of two consanguineous families with ARNSHL from Tunisia and Turkey revealed two novel causative COL11A2 mutations, c.109G > T (p.Ala37Ser) and c.2662C > A (p.Pro888Thr). The variants identified co-segregated with deafness in both families. All homozygous individuals in those families had early onset profound hearing loss across all frequencies without syndromic findings. The variants are predicted to be damaging the protein function. The p.Pro888Thr mutation affects a -Gly-X–Y- triplet repeat motif. The novel p.Ala37Ser is the first missense mutation located in the NC4 domain of the COL11A2 protein. Structural model suggests that this mutation will likely obliterate, or at least partially compromise, the ability of NC4 domain to interact with its cognate ligands. In conclusion, we confirm that COL11A2 mutations cause ARNSHL and broaden the mutation spectrum that may shed new light on genotype–phenotype correlation for the associated phenotypes and clinical follow-up. PMID:25633957

  4. Mitochondrial Hsp60 Chaperonopathy Causes an Autosomal-Recessive Neurodegenerative Disorder Linked to Brain Hypomyelination and Leukodystrophy

    PubMed Central

    Magen, Daniella; Georgopoulos, Costa; Bross, Peter; Ang, Debbie; Segev, Yardena; Goldsher, Dorit; Nemirovski, Alexandra; Shahar, Eli; Ravid, Sarit; Luder, Anthony; Heno, Bayan; Gershoni-Baruch, Ruth; Skorecki, Karl; Mandel, Hanna

    2008-01-01

    Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration. PMID:18571143

  5. Mitochondrial hsp60 chaperonopathy causes an autosomal-recessive neurodegenerative disorder linked to brain hypomyelination and leukodystrophy.

    PubMed

    Magen, Daniella; Georgopoulos, Costa; Bross, Peter; Ang, Debbie; Segev, Yardena; Goldsher, Dorit; Nemirovski, Alexandra; Shahar, Eli; Ravid, Sarit; Luder, Anthony; Heno, Bayan; Gershoni-Baruch, Ruth; Skorecki, Karl; Mandel, Hanna

    2008-07-01

    Hypomyelinating leukodystrophies (HMLs) are disorders involving aberrant myelin formation. The prototype of primary HMLs is the X-linked Pelizaeus-Merzbacher disease (PMD) caused by mutations in PLP1. Recently, homozygous mutations in GJA12 encoding connexin 47 were found in patients with autosomal-recessive Pelizaeus-Merzbacher-like disease (PMLD). However, many patients of both genders with PMLD carry neither PLP1 nor GJA12 mutations. We report a consanguineous Israeli Bedouin kindred with clinical and radiological findings compatible with PMLD, in which linkage to PLP1 and GJA12 was excluded. Using homozygosity mapping and mutation analysis, we have identified a homozygous missense mutation (D29G) not previously described in HSPD1, encoding the mitochondrial heat-shock protein 60 (Hsp60) in all affected individuals. The D29G mutation completely segregates with the disease-associated phenotype. The pathogenic effect of D29G on Hsp60-chaperonin activity was verified by an in vivo E. coli complementation assay, which demonstrated compromised ability of the D29G-Hsp60 mutant protein to support E. coli survival, especially at high temperatures. The disorder, which we have termed MitCHAP-60 disease, can be distinguished from spastic paraplegia 13 (SPG13), another Hsp60-associated autosomal-dominant neurodegenerative disorder, by its autosomal-recessive inheritance pattern, as well as by its early-onset, profound cerebral involvement and lethality. Our findings suggest that Hsp60 defects can cause neurodegenerative pathologies of varying severity, not previously suspected on the basis of the SPG13 phenotype. These findings should help to clarify the important role of Hsp60 in myelinogenesis and neurodegeneration.

  6. ADCK3, an Ancestral Kinase, Is Mutated in a Form of Recessive Ataxia Associated with Coenzyme Q10 Deficiency

    PubMed Central

    Lagier-Tourenne, Clotilde; Tazir, Meriem; López, Luis Carlos; Quinzii, Catarina M.; Assoum, Mirna; Drouot, Nathalie; Busso, Cleverson; Makri, Samira; Ali-Pacha, Lamia; Benhassine, Traki; Anheim, Mathieu; Lynch, David R.; Thibault, Christelle; Plewniak, Frédéric; Bianchetti, Laurent; Tranchant, Christine; Poch, Olivier; DiMauro, Salvatore; Mandel, Jean-Louis; Barros, Mario H.; Hirano, Michio; Koenig, Michel

    2008-01-01

    Muscle coenzyme Q10 (CoQ10 or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ10 biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ10 deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ10 in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ10 biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production. PMID:18319074

  7. The effect of consanguineous marriage on reading disability in the Arab community.

    PubMed

    Abu-Rabia, Salim; Maroun, Lateefeh

    2005-02-01

    The present study examined the effect of consanguineous marriage in the Arab community on reading disabilities of offspring. It examined whether the rate of reading disabilities was higher among offspring of first-cousin parents than offspring of unrelated parents; and whether reading-disabled children of first-cousin parents were more disabled in phonological awareness and phonological decoding than reading-disabled children of unrelated parents and normally reading younger children. These questions were investigated among 814 pupils of the 4th, 5th, and 6th grades, using word recognition and reading comprehension tests. Two experimental groups were chosen from this population. These were a reading-disabled group of 22 pupils who were children of first-cousin marriages and 21 pupils who were children of unrelated parents. A control group was also selected, consisting of 21 younger normally reading pupils at the same reading level. All the groups were tested on non-words, real words, phonological, orthographic and working memory measures. The results indicated that the rate of reading disabilities among children of first-cousin parents was higher than that of with children of second-cousin parents, distantly related parents, or unrelated parents. Further, no differences were found in phonological awareness and decoding between the two reading-disabled groups. Moreover, the results indicate a significant advantage of the younger normal readers over the reading-disabled children in the measures of phonological awareness, decoding, and orthographical knowledge that requires spelling. However, in reading common words and choosing words in context, the performance of the reading-disabled groups and the normally reading group were similar. It has been suggested that further research is needed to evaluate the role of intelligence, nevertheless our results provide new evidence for a genetic basis to reading disabilities. PMID:15747804

  8. The effect of consanguineous marriage on reading disability in the Arab community.

    PubMed

    Abu-Rabia, Salim; Maroun, Lateefeh

    2005-02-01

    The present study examined the effect of consanguineous marriage in the Arab community on reading disabilities of offspring. It examined whether the rate of reading disabilities was higher among offspring of first-cousin parents than offspring of unrelated parents; and whether reading-disabled children of first-cousin parents were more disabled in phonological awareness and phonological decoding than reading-disabled children of unrelated parents and normally reading younger children. These questions were investigated among 814 pupils of the 4th, 5th, and 6th grades, using word recognition and reading comprehension tests. Two experimental groups were chosen from this population. These were a reading-disabled group of 22 pupils who were children of first-cousin marriages and 21 pupils who were children of unrelated parents. A control group was also selected, consisting of 21 younger normally reading pupils at the same reading level. All the groups were tested on non-words, real words, phonological, orthographic and working memory measures. The results indicated that the rate of reading disabilities among children of first-cousin parents was higher than that of with children of second-cousin parents, distantly related parents, or unrelated parents. Further, no differences were found in phonological awareness and decoding between the two reading-disabled groups. Moreover, the results indicate a significant advantage of the younger normal readers over the reading-disabled children in the measures of phonological awareness, decoding, and orthographical knowledge that requires spelling. However, in reading common words and choosing words in context, the performance of the reading-disabled groups and the normally reading group were similar. It has been suggested that further research is needed to evaluate the role of intelligence, nevertheless our results provide new evidence for a genetic basis to reading disabilities.

  9. Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life

    PubMed Central

    Thevenon, Julien; Milh, Mathieu; Feillet, François; St-Onge, Judith; Duffourd, Yannis; Jugé, Clara; Roubertie, Agathe; Héron, Delphine; Mignot, Cyril; Raffo, Emmanuel; Isidor, Bertrand; Wahlen, Sandra; Sanlaville, Damien; Villeneuve, Nathalie; Darmency-Stamboul, Véronique; Toutain, Annick; Lefebvre, Mathilde; Chouchane, Mondher; Huet, Frédéric; Lafon, Arnaud; de Saint Martin, Anne; Lesca, Gaetan; El Chehadeh, Salima; Thauvin-Robinet, Christel; Masurel-Paulet, Alice; Odent, Sylvie; Villard, Laurent; Philippe, Christophe; Faivre, Laurence; Rivière, Jean-Baptiste

    2014-01-01

    Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due to mutations in the same gene, and we performed exome sequencing in three affected individuals. Analysis of rare variants in genes consistent with an autosomal-recessive mode of inheritance led to identification of mutations in SLC13A5, which encodes the cytoplasmic sodium-dependent citrate carrier, notably expressed in neurons. Disease association was confirmed by cosegregation analysis in additional family members. Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with compound heterozygous mutations of SLC13A5 and a similar clinical presentation as the index subjects. Mutations affected key residues for sodium binding, which is critical for citrate transport. These findings underline the value of careful clinical characterization for genetic investigations in highly heterogeneous conditions such as EE and further highlight the role of citrate metabolism in epilepsy. PMID:24995870

  10. Whole-exome sequencing reveals a novel frameshift mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in the Indian population.

    PubMed

    Zhou, Yu; Saikia, Bibhuti B; Jiang, Zhilin; Zhu, Xiong; Liu, Yuqing; Huang, Lulin; Kim, Ramasamy; Yang, Yin; Qu, Chao; Hao, Fang; Gong, Bo; Tai, Zhengfu; Niu, Lihong; Yang, Zhenglin; Sundaresan, Periasamy; Zhu, Xianjun

    2015-10-01

    Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 50 genes. To identify genetic mutations underlying autosomal recessive RP (arRP), we performed whole-exome sequencing study on two consanguineous marriage Indian families (RP-252 and RP-182) and 100 sporadic RP patients. Here we reported novel mutation in FAM161A in RP-252 and RP-182 with two patients affected with RP in each family. The FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. By whole-exome sequencing we identified several homozygous genomic regions, one of which included the recently identified FAM161A gene mutated in RP28-linked arRP. Sequencing analysis revealed the presence of a novel homozygous frameshift mutation p.R592FsX2 in both patients of family RP-252 and family RP-182. In 100 sporadic Indian RP patients, this novel homozygous frameshift mutation p.R592FsX2 was identified in one sporadic patient ARRP-S-I-46 by whole-exome sequencing and validated by Sanger sequencing. Meanwhile, this homozygous frameshift mutation was absent in 1000 ethnicity-matched control samples screened by direct Sanger sequencing. In conclusion, we identified a novel homozygous frameshift mutations of RP28-linked RP gene FAM161A in Indian population.

  11. Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life.

    PubMed

    Thevenon, Julien; Milh, Mathieu; Feillet, François; St-Onge, Judith; Duffourd, Yannis; Jugé, Clara; Roubertie, Agathe; Héron, Delphine; Mignot, Cyril; Raffo, Emmanuel; Isidor, Bertrand; Wahlen, Sandra; Sanlaville, Damien; Villeneuve, Nathalie; Darmency-Stamboul, Véronique; Toutain, Annick; Lefebvre, Mathilde; Chouchane, Mondher; Huet, Frédéric; Lafon, Arnaud; de Saint Martin, Anne; Lesca, Gaetan; El Chehadeh, Salima; Thauvin-Robinet, Christel; Masurel-Paulet, Alice; Odent, Sylvie; Villard, Laurent; Philippe, Christophe; Faivre, Laurence; Rivière, Jean-Baptiste

    2014-07-01

    Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due to mutations in the same gene, and we performed exome sequencing in three affected individuals. Analysis of rare variants in genes consistent with an autosomal-recessive mode of inheritance led to identification of mutations in SLC13A5, which encodes the cytoplasmic sodium-dependent citrate carrier, notably expressed in neurons. Disease association was confirmed by cosegregation analysis in additional family members. Screening of 68 additional unrelated individuals with early-onset epileptic encephalopathy for SLC13A5 mutations led to identification of one additional subject with compound heterozygous mutations of SLC13A5 and a similar clinical presentation as the index subjects. Mutations affected key residues for sodium binding, which is critical for citrate transport. These findings underline the value of careful clinical characterization for genetic investigations in highly heterogeneous conditions such as EE and further highlight the role of citrate metabolism in epilepsy.

  12. Autosomal recessive spastic paraplegia (SPG45) with mental retardation maps to 10q24.3-q25.1.

    PubMed

    Dursun, Umut; Koroglu, Cigdem; Kocasoy Orhan, Elif; Ugur, Sibel Aylin; Tolun, Aslihan

    2009-10-01

    Hereditary spastic paraplegias (HSPs) are characterized by progressive spasticity in the lower limbs. They are clinically heterogeneous, and pure forms as well as complicated forms with other accompanying clinical findings are known. HSPs are also genetically heterogeneous. We performed clinical and genetic studies in a consanguineous family with five affected members. A genome scan using 405 microsatellite markers for eight members of the family identified candidate gene loci, and subsequent fine mapping in 16 members identified the gene locus responsible for the HSP. The clinical manifestations were very early onset spastic paraplegia (SPG) accompanied by mental retardation and ocular signs. The gene locus was identified as the interval 102.05-106.64 Mbp on chromosome 10. Gene MRPL43 was analyzed in the patients. No mutation but high levels of mRNA were detected. We have mapped a novel autosomal recessive complicated form of HSP (SPG45) to a 4.6-Mbp region at 10q24.3-q25.1 with multipoint logarithm of odds scores >4.5.

  13. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability.

    PubMed

    Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J M; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein; Arshad Rafiq, Muhammad; Mozhdehipanah, Hossein; Rashidinejad, Ali; Samiei, Shahram; Ghadami, Mohsen; Windpassinger, Christian; Gillessen-Kaesbach, Gabriele; Tzschach, Andreas; Ahmed, Iltaf; Mikhailov, Anna; Stavropoulos, D James; Carter, Melissa T; Keshavarz, Soraya; Ayub, Muhammad; Najmabadi, Hossein; Liu, Xudong; Ropers, Hans Hilger; Macheroux, Peter; Vincent, John B

    2015-10-15

    Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability.

  14. Mutations in the histamine N-methyltransferase gene, HNMT, are associated with nonsyndromic autosomal recessive intellectual disability

    PubMed Central

    Heidari, Abolfazl; Tongsook, Chanakan; Najafipour, Reza; Musante, Luciana; Vasli, Nasim; Garshasbi, Masoud; Hu, Hao; Mittal, Kirti; McNaughton, Amy J. M.; Sritharan, Kumudesh; Hudson, Melissa; Stehr, Henning; Talebi, Saeid; Moradi, Mohammad; Darvish, Hossein; Arshad Rafiq, Muhammad; Mozhdehipanah, Hossein; Rashidinejad, Ali; Samiei, Shahram; Ghadami, Mohsen; Windpassinger, Christian; Gillessen-Kaesbach, Gabriele; Tzschach, Andreas; Ahmed, Iltaf; Mikhailov, Anna; Stavropoulos, D. James; Carter, Melissa T.; Keshavarz, Soraya; Ayub, Muhammad; Najmabadi, Hossein; Liu, Xudong; Ropers, Hans Hilger; Macheroux, Peter; Vincent, John B.

    2015-01-01

    Histamine (HA) acts as a neurotransmitter in the brain, which participates in the regulation of many biological processes including inflammation, gastric acid secretion and neuromodulation. The enzyme histamine N-methyltransferase (HNMT) inactivates HA by transferring a methyl group from S-adenosyl-l-methionine to HA, and is the only well-known pathway for termination of neurotransmission actions of HA in mammalian central nervous system. We performed autozygosity mapping followed by targeted exome sequencing and identified two homozygous HNMT alterations, p.Gly60Asp and p.Leu208Pro, in patients affected with nonsyndromic autosomal recessive intellectual disability from two unrelated consanguineous families of Turkish and Kurdish ancestry, respectively. We verified the complete absence of a functional HNMT in patients using in vitro toxicology assay. Using mutant and wild-type DNA constructs as well as in silico protein modeling, we confirmed that p.Gly60Asp disrupts the enzymatic activity of the protein, and that p.Leu208Pro results in reduced protein stability, resulting in decreased HA inactivation. Our results highlight the importance of inclusion of HNMT for genetic testing of individuals presenting with intellectual disability. PMID:26206890

  15. Autosomal Recessive Disorder Otospondylomegaepiphyseal Dysplasia Is Associated with Loss-of-Function Mutations in the COL11A2 Gene

    PubMed Central

    Melkoniemi, MiiaÂ; Brunner, Han G.Â; Manouvrier, SylvieÂ; Hennekam, RaoulÂ; Superti-Furga, AndreaÂ; Kääriäinen, HelenaÂ; Pauli, Richard M.Â; van Essen, TonÂ; Warman, Matthew L.Â; Bonaventure, JackyÂ; Miny, PeterÂ; Ala-Kokko, LeenaÂ

    2000-01-01

    Summary Otospondylomegaepiphyseal dysplasia (OSMED) is an autosomal recessive skeletal dysplasia accompanied by severe hearing loss. The phenotype overlaps that of the autosomal dominant disorders—Stickler and Marshall syndromes—but can be distinguished by disproportionately short limbs, severe hearing loss, and lack of ocular involvement. In one family with OSMED, a homozygous Gly→Arg substitution has been described in COL11A2, which codes for the α2 chain of type XI collagen. We report seven further families with OSMED. All affected individuals had a remarkably similar phenotype: profound sensorineural hearing loss, skeletal dysplasia with limb shortening and large epiphyses, cleft palate, an extremely flat face, hypoplasia of the mandible, a short nose with anteverted nares, and a flat nasal bridge. We screened affected individuals for mutations in COL11A2 and found different mutations in each family. Individuals from four families, including three with consanguineous parents, were homozygous for mutations. Individuals from three other families, in whom parents were nonconsanguineous, were compound heterozygous. Of the 10 identified mutations, 9 are predicted to cause premature termination of translation, and 1 is predicted to cause an in-frame deletion. We conclude that the OSMED phenotype is highly homogenous and results from homozygosity or compound heterozygosity for COL11A2 mutations, most of which are predicted to cause complete absence of α2(XI) chains. PMID:10677296

  16. Impact of recession on Swiss pension program.

    PubMed

    McArdle, F B

    1978-04-01

    Legislation drafted in Switzerland in 1975--77 aims at countering the effects of inflation and recession by bringing increased revenues into the system, reducing expenditures, devising a mechanism to adjust pensions automatically, and improving income maintenance for the unemployed. The proposed legislation to place the social security system on a sound financial basis now needs voter approval in a referendum. Swiss voters meanwhile rejected (in mid-1977) a government-proposed value-added tax designed to finance increasing government contributions during 1978-82. Still to be resolved, therefore, is the problem of how the government will finance higher contributions and still achieve its staged goal of a balanced budget. PMID:644419

  17. Intimate Partner Violence in the Great Recession.

    PubMed

    Schneider, Daniel; Harknett, Kristen; McLanahan, Sara

    2016-04-01

    In the United States, the Great Recession was marked by severe negative shocks to labor market conditions. In this study, we combine longitudinal data from the Fragile Families and Child Wellbeing Study with U.S. Bureau of Labor Statistics data on local area unemployment rates to examine the relationship between adverse labor market conditions and mothers' experiences of abusive behavior between 2001 and 2010. Unemployment and economic hardship at the household level were positively related to abusive behavior. Further, rapid increases in the unemployment rate increased men's controlling behavior toward romantic partners even after we adjust for unemployment and economic distress at the household level. We interpret these findings as demonstrating that the uncertainty and anticipatory anxiety that go along with sudden macroeconomic downturns have negative effects on relationship quality, above and beyond the effects of job loss and material hardship. PMID:27003136

  18. Did the Great Recession influence retirement plans?

    PubMed

    Szinovacz, Maximiliane E; Davey, Adam; Martin, Lauren

    2015-04-01

    The recent recession constitutes one of the macro forces that may have influenced workers' retirement plans. We evaluate a multilevel model that addresses the influence of macro-, meso-, and micro-level factors on retirement plans, changes in these plans, and expected retirement age. Using data from Waves 8 and 9 of the Health and Retirement Study (N=2,618), we find that individuals with defined benefit plans are more prone to change toward plans to stop work before the stock market declined, whereas the opposite trend holds for those without pensions. Debts, ability to reduce work hours, and firm unionization also influenced retirement plans. Findings suggest retirement planning education may be particularly important for workers without defined pensions, especially in times of economic volatility.

  19. Parents' Victory in Reclaiming Recess for Their Children

    ERIC Educational Resources Information Center

    Zygmunt-Fillwalk, Eva; Bilello, Teresa Evanko

    2005-01-01

    This article discusses the issue of schools limiting the opportunities for children's physical, cognitive, social-emotional, and creative development that recess affords. Red Rover, hopscotch, jump rope, chase, telling secrets, hanging out, making friends, losing friends--these familiar pursuits of childhood recess are vividly memorable. While…

  20. Physical Education and Recess Contributions to Sixth Graders' Physical Activity

    ERIC Educational Resources Information Center

    Gutierrez, Ashley A.; Williams, Skip M.; Coleman, Margaret M.; Garrahy, Deborah A.; Laurson, Kelly R.

    2016-01-01

    Background: The purpose of this study was twofold: (a) to examine the percentage of the daily threshold (12,000 steps) that physical education (PE) class and recess contribute to 6th grade students' overall daily physical activity (PA) and (b) to examine the relationships between gender, PA outside of school, BMI, and steps during both recess and…

  1. Social Skills Intervention during Elementary School Recess: A Visual Analysis.

    ERIC Educational Resources Information Center

    Anderson-Butcher, Dawn; Newsome, W. Sean; Nay, Stephanie

    2003-01-01

    This study builds on two studies that explored the effect of a social skills intervention on problem behaviors displayed by elementary school children during recess. Findings conclude that social skills intervention significantly decreased problem behaviors among school children at recess. Implications for behavioral management and healthy school…

  2. The Impact of the Recession on College Students

    ERIC Educational Resources Information Center

    Berg-Cross, Linda; Green, Rodney

    2010-01-01

    This article had three goals: (a) to provide a brief economic review of the relationship between recessionary times, institutional reactions, and the life trajectory of recession-era college students; (b) to discuss the recession-related psychosocial stressors facing today's college students; and (c) to discuss how counseling centers can help…

  3. Withholding Recess from Elementary School Students: Policies Matter

    ERIC Educational Resources Information Center

    Turner, Lindsey; Chriqui, Jamie F.; Chaloupka, Frank J.

    2013-01-01

    Background: Recess is a key aspect of a healthy elementary school environment and helps to keep students physically active during the school day. Although national organizations recommend that students not be withheld from recess, this practice occurs in schools. This study examined whether district policies were associated with school practices…

  4. Children's Recess Physical Activity: Movement Patterns and Preferences

    ERIC Educational Resources Information Center

    Woods, Amelia Mays; Graber, Kim C.; Daum, David Newman

    2012-01-01

    The benefits of recess can be reaped by all students regardless of socioeconomic status, race, or gender and at relatively little cost. The purpose of this study was to examine physical activity (PA) variables related to the recess PA patterns of third and fourth grade children and the social preferences and individuals influencing their PA…

  5. The Fourth R: Recess and Its Link to Learning.

    ERIC Educational Resources Information Center

    Waite-Stupiansky, Sandra; Findlay, Marcia

    2001-01-01

    Review of research on recess shows how its presence or absence affects children's brain development, health and physical development, attention, memory, social and emotional adjustment, language development, and classroom behavior. Despite demonstrated benefits, recess is endangered by pressures on schools to increase achievement. (Contains 52…

  6. Who Suffers during Recessions? NBER Working Paper No. 17951

    ERIC Educational Resources Information Center

    Hoynes, Hilary W.; Miller, Douglas L.; Schaller, Jessamyn

    2012-01-01

    In this paper we examine how business cycles affect labor market outcomes in the United States. We conduct a detailed analysis of how cycles affect outcomes differentially across persons of differing age, education, race, and gender, and we compare the cyclical sensitivity during the Great Recession to that in the early 1980s recession. We present…

  7. "United Pedicle Flap" for management of multiple gingival recessions.

    PubMed

    Chopra, Aditi; Sivaraman, Karthik; Bhat, Subraya Giliyar

    2016-01-01

    Numerous surgical procedures have evolved and are being modified with time to treat gingival recession by manipulating gingival or mucosal tissues in various ways. However, the decision to choose the most appropriate technique for a given recession site still remains a challenging task for clinicians. Mucogingival deformities such as shallow vestibule, frenal pull, or inadequate attached gingiva complicate the decision and limit the treatment options to an invasive procedure involving soft tissue grafts. The situation is further comprised if there is a nonavailability of adequate donor tissue and patients' unwillingness for procedures involving a second surgical site. In such situations, the recession either remains untreated or has poor treatment outcomes. This case report presents a modified pedicle graft technique for treatment of multiple gingival recessions with shallow vestibule and inadequate attached gingiva. The technique is a promising therapeutic alternative to invasive surgical procedures such as soft tissue grafts for treatment of multiple gingival recessions. PMID:27563212

  8. Cultural adaptation of preschool PATHS (Promoting Alternative Thinking Strategies) curriculum for Pakistani children.

    PubMed

    Inam, Ayesha; Tariq, Pervaiz N; Zaman, Sahira

    2015-06-01

    Cultural adaptation of evidence-based programmes has gained importance primarily owing to its perceived impact on the established effectiveness of a programme. To date, many researchers have proposed different frameworks for systematic adaptation process. This article presents the cultural adaptation of preschool Promoting Alternative Thinking Strategies (PATHS) curriculum for Pakistani children using the heuristic framework of adaptation (Barrera & Castro, 2006). The study was completed in four steps: information gathering, preliminary adaptation design, preliminary adaptation test and adaptation refinement. Feedbacks on programme content suggested universality of the core programme components. Suggested changes were mostly surface structure: language, presentation of materials, conceptual equivalence of concepts, training needs of implementation staff and frequency of programme delivery. In-depth analysis was done to acquire cultural equivalence. Pilot testing of the outcome measures showed strong internal consistency. The results were further discussed with reference to similar work undertaken in other cultures.

  9. Perceptions and experiences with nursing care: a study of Pakistani (Urdu) communities in the United Kingdom.

    PubMed

    Cortis, J D

    2000-04-01

    The population of the United Kingdom reflects rich cultural diversity. Hence, nursing must respond to the challenges of meeting the needs of different ethnic groups and fulfilL the requirements of the Code of Professional Conduct. This article presents the findings of a study using grounded theory to explore the lived experience of Pakistani (Urdu-speaking) communities that received nursing care in a hospital setting in the United Kingdom. The study reflects national initiatives toward "consumer led" health care delivery. The findings illustrate a lack of congruence between the group's expectations and their experiences. Nurses were perceived to have a poor understanding of ethnic needs, portraying ethnocentric attitudes and behaviour. The participants attributed the lack of congruence mainly to the presence of racism in British health care systems. The author suggests possible changes at the strategic, managerial, and educational levels of health care delivery.

  10. Slow post meal walking reduces the blood glucose response: an exploratory study in female Pakistani immigrants.

    PubMed

    Lunde, Marianne S H; Hjellset, Victoria Telle; Høstmark, Arne T

    2012-10-01

    Postprandial physical activity may blunt the blood glucose response. In diabetes prone female immigrants only slow walking is regularly performed raising the question of whether also this type of physical activity can attenuate their post meal blood glucose elevation. Using a cross over design, 11 female Pakistani immigrants living in Oslo were recruited to participate in three experiments where their blood glucose concentration was measured every 15 min for 2 h after intake of a high glycemic food, either while resting after the meal or doing very light post meal walking of two durations. Postprandial blood glucose peak value and incremental area under the 2 h blood glucose curve decreased with increasing duration of slow post meal walking. Also the blood pressure was lowered. Post meal walking can strongly attenuate the glycemic response to carbohydrates and reduce blood pressure in a high risk group of immigrants.

  11. Ethnomedicinal and phytochemical review of Pakistani medicinal plants used as antibacterial agents against Escherichia coli

    PubMed Central

    2014-01-01

    Medicinal plants have always been part of human culture and have the potential to cure different diseases caused by microorganisms. In Pakistan, biologists are mainly focusing on plants’ antimicrobial activities against Escherichia coli due to its increasing resistance to antibiotics. In total, extracts from 34 ethnomedicinally valuable Pakistani plants were reported for in-vitro anti-E. coli activities. Mostly methanolic extracts of medicinal plants were used in different studies, which have shown comparatively higher inhibitory activities against E. coli than n-hexane and aqueous extracts. It has been found that increasing concentration (mg/ml) of methanolic extract can significantly increase (p < 0.01) anti-E. coli activities. Not all medicinal plants are extracted in solvents others than above, which should also be tested against E. coli. Moreover, medicinal plant species must be fully explored phytochemically, which may lead to the development of new drugs. PMID:25135359

  12. RATIONALIZED AND COMPLEMENTARY FINDINGS OF SILYMARIN (MILK THISTLE) IN PAKISTANI HEALTHY VOLUNTEERS.

    PubMed

    Ashraf, Muhammad; Abid, Farah; Riffat, Sualeha; Bashir, Sajid; Iqbal, Javed; Sarfraz, Muhammad; Afzal, Attia; Zaheer, Muhammad

    2015-01-01

    The aim of the work was to examine the influence of gender on pharmacokinetics of silymarin; a basic constituent of medicinal herb "milk thistle" (Silybum marianum). The presented work is the extension of published work of Usman et al. (16). The comparative parallel design pharmacokinetic study was conducted in Pakistani healthy volunteers (male and female) receiving a single 200 mg oral dose of silymarin. Sixteen subjects (8 males and 8 females) were enrolled and completed the 12 h study. Blood screening was done on HPLC and the pharmacokinetic parameters were calculated by APO, 3.2 Ver. software using non-compartmental and two compartment model approaches. A significant difference (p < 0.05) was observed in almost all calculated pharmacokinetic parameters of silymarin in male and female. Clinically, the silymarin has been underestimated in the previous study. Gender based clinical investigations should be directed in the future on other flavono-lignans of 'milk thistle' as well.

  13. Diagnostic Yield of Chromosomal Microarray Analysis in a Cohort of Patients with Autism Spectrum Disorders from a Highly Consanguineous Population.

    PubMed

    Al-Mamari, Watfa; Al-Saegh, Abeer; Al-Kindy, Adila; Bruwer, Zandre; Al-Murshedi, Fathiya; Al-Thihli, Khalid

    2015-08-01

    Autism Spectrum Disorders are a complicated group of disorders characterized with heterogeneous genetic etiologies. The genetic investigations for this group of disorders have expanded considerably over the past decade. In our study we designed a tired approach and studied the diagnostic yield of chromosomal microarray analysis on patients referred to the Genetic and Developmental Medicine clinic in Sultan Qaboos University in Oman for autism spectrum disorders in a highly consanguineous population. Copy number variants were seen in 27% of our studied cohort of patients and it was strongly associated with dysmorphic features and congenital anomalies. PMID:25703031

  14. Public stigma associated with mental illnesses in Pakistani university students: a cross sectional survey

    PubMed Central

    Zubair, Muhammad; Ghulam, Hamzah; Wajih Ullah, Muhammad; Zubair Tariq, Muhammad

    2014-01-01

    Background. The objectives of the study were to explore the knowledge and attitudes of Pakistani university students toward mental illnesses. People with mental illnesses are challenged not only by their symptoms but also by the prejudices associated with their illness. Acknowledging the stigma of mental illness should be the first essential step toward devising an appropriate treatment plan. Methods. A cross-sectional survey was conducted at the University of Punjab, Lahore, CMH Lahore Medical and Dental College, Lahore, and University of Sargodha, Sub-campus Lahore, from February to May 2014. The self-administered questionnaire consisted of three sections: demographics, general knowledge of psychiatric illnesses, and Community Attitudes towards Mental Illnesses (CAMI) Scale. The questionnaire was distributed to 650 participants enrolled in different disciplines (Social Sciences, Medicine and Formal Sciences). Results. Response rate was 81% (527/650 respondents). Mean age was 20.98 years. Most of the students (331, 62.8%) had an urban background and studied Social Sciences (238, 45.2%). Four hundred and eighteen respondents (79.3%) considered religion very important and most respondents considered psychiatrists (334, 63.4%) and spiritual leaders (72, 13.7%) to be best able to treat mental illnesses. One hundred and sixty nine respondents (32.1%) considered black magic to be a cause of mental illness. Only 215 (41%) respondents had ever read an article on mental illnesses. Multiple regression analysis revealed study discipline, exposure, perceived causes of mental illnesses and superstitions to be significantly associated with attitudes towards mental illnesses (p < .05). Conclusion. Although low awareness and exposure were found in this sample of Pakistani university students, their attitude towards mental illnesses was generally positive. Most respondents gave supernatural explanations for mental illnesses but only a few believed that spiritual leaders can play a

  15. Characterization of High-Value Bioactives in Some Selected Varieties of Pakistani Rice (Oryza sativa L.)

    PubMed Central

    Zubair, Muhammad; Anwar, Farooq; Ashraf, Muhammad; Uddin, Md. Kamal

    2012-01-01

    The present study reports the composition and variation of fatty acids, sterols, tocopherols and γ-oryzanol among selected varieties namely Basmati Super, Basmati 515, Basmati 198, Basmati 385, Basmati 2000, Basmati 370, Basmati Pak, KSK-139, KS-282 and Irri-6 of Pakistani rice (Oryza sativa L). Oil content extracted with n-hexane from different varieties of brown rice seed (unpolished rice) ranged from 1.92% to 2.72%. Total fatty acid contents among rice varieties tested varied between 18240 and 25840 mg/kg brown rice seed. The rice tested mainly contained oleic (6841–10952 mg/kg) linoleic (5453–7874 mg/kg) and palmitic acid (3613–5489 mg/kg). The amounts of total phytosterols (GC and GC-MS analysis), with main contribution from β-sitosterol (445–656 mg/kg), campesterol (116–242 mg/kg), Δ5-avenasterol (89–178 mg/kg) and stigmasterol (75–180 mg/kg) were established to be 739.4 to 1330.4 mg/kg rice seed. The content of α-, γ- and δ-tocopherols as analyzed by HPLC varied from 39.0–76.1, 21.6–28.1 and 6.5–16.5 mg/kg rice seed, respectively. The amounts of different γ-oryzanol components (HPLC data), identified as cycloartenyl ferulate, 24-methylene cycloartanyl ferulate, campesteryl ferulate and β-sitosteryl ferulate, were in the range of 65.5–103.6, 140.2–183.1, 29.8–45.5 and 8.6–10.4 mg/kg rice seed, respectively. Overall, the concentration of these bioactives was higher in the Basmati rice cultivars showing their functional food superiority. In conclusion, the tested varieties of Pakistani rice, especially the Basmati cultivars, can provide best ingredients for functional foods. PMID:22605998

  16. Prediction values for the ventilatory capacity in male West Pakistani workers in the United Kingdom

    PubMed Central

    Malik, M. A.; Moss, E.; Lee, W. R.

    1972-01-01

    The ventilatory functions (forced vital capacity, forced expiratory volume in one second, and peak expiratory flow rate) of West Pakistani immigrants working near Manchester were measured. There were 198 `normal' healthy adult workers aged 25 to 60 years and 129 workers aged 16 to 24 years. The subjects were considered `normal' if they did not admit to persistent cough and phlegm. The regression equations on age and height for the two groups are presented together with the corresponding nomograms for the adult group. Ventilatory function reached its maximum between the ages of 25 and 30 years; smokers and dust-exposed subjects did not differ significantly from non-smokers and non-dust-exposed subjects (P>0·1). This was probably due to their relatively light smoking habits and the short duration of dust exposure. The effects of age, in workers over the age of 25 years, and the predominant effects of height on the FVC, FEV1·0, and PEFR are similar to those found in other studies. The ventilatory capacity of the subjects was found to be somewhat lower than that of Caucasians, about equal to that of Negroes living in America, and higher than that of Indians of Asian origin living in Guyana or of Bantu Negroes in South Africa. The predicted FEV1·0/FVC% in the West Pakistani subjects is a little higher than any calculated from the results of other authors, but its regression on age is consistent with the findings of other studies and, therefore, can be used in clinical practice to assess the pulmonary conductance. PMID:5083729

  17. Public stigma associated with mental illnesses in Pakistani university students: a cross sectional survey.

    PubMed

    Waqas, Ahmed; Zubair, Muhammad; Ghulam, Hamzah; Wajih Ullah, Muhammad; Zubair Tariq, Muhammad

    2014-01-01

    Background. The objectives of the study were to explore the knowledge and attitudes of Pakistani university students toward mental illnesses. People with mental illnesses are challenged not only by their symptoms but also by the prejudices associated with their illness. Acknowledging the stigma of mental illness should be the first essential step toward devising an appropriate treatment plan. Methods. A cross-sectional survey was conducted at the University of Punjab, Lahore, CMH Lahore Medical and Dental College, Lahore, and University of Sargodha, Sub-campus Lahore, from February to May 2014. The self-administered questionnaire consisted of three sections: demographics, general knowledge of psychiatric illnesses, and Community Attitudes towards Mental Illnesses (CAMI) Scale. The questionnaire was distributed to 650 participants enrolled in different disciplines (Social Sciences, Medicine and Formal Sciences). Results. Response rate was 81% (527/650 respondents). Mean age was 20.98 years. Most of the students (331, 62.8%) had an urban background and studied Social Sciences (238, 45.2%). Four hundred and eighteen respondents (79.3%) considered religion very important and most respondents considered psychiatrists (334, 63.4%) and spiritual leaders (72, 13.7%) to be best able to treat mental illnesses. One hundred and sixty nine respondents (32.1%) considered black magic to be a cause of mental illness. Only 215 (41%) respondents had ever read an article on mental illnesses. Multiple regression analysis revealed study discipline, exposure, perceived causes of mental illnesses and superstitions to be significantly associated with attitudes towards mental illnesses (p < .05). Conclusion. Although low awareness and exposure were found in this sample of Pakistani university students, their attitude towards mental illnesses was generally positive. Most respondents gave supernatural explanations for mental illnesses but only a few believed that spiritual leaders can play a

  18. Urbanization and the global malaria recession

    PubMed Central

    2013-01-01

    Background The past century has seen a significant contraction in the global extent of malaria transmission, resulting in over 50 countries being declared malaria free, and many regions of currently endemic countries eliminating the disease. Moreover, substantial reductions in transmission have been seen since 1900 in those areas that remain endemic today. Recent work showed that this malaria recession was unlikely to have been driven by climatic factors, and that control measures likely played a significant role. It has long been considered, however, that economic development, and particularly urbanization, has also been a causal factor. The urbanization process results in profound socio-economic and landscape changes that reduce malaria transmission, but the magnitude and extent of these effects on global endemicity reductions are poorly understood. Methods Global data at subnational spatial resolution on changes in malaria transmission intensity and urbanization trends over the past century were combined to examine the relationships seen over a range of spatial and temporal scales. Results/Conclusions A consistent pattern of increased urbanization coincident with decreasing malaria transmission and elimination over the past century was found. Whilst it remains challenging to untangle whether this increased urbanization resulted in decreased transmission, or that malaria reductions promoted development, the results point to a close relationship between the two, irrespective of national wealth. The continuing rapid urbanization in malaria-endemic regions suggests that such malaria declines are likely to continue, particularly catalyzed by increasing levels of direct malaria control. PMID:23594701

  19. CONSANGUINITY AND INBREEDING COEFFICIENT IN TRIBAL PASHTUNS INHABITING THE TURBULENT AND WAR-AFFECTED TERRITORY OF BAJAUR AGENCY, NORTH-WEST PAKISTAN.

    PubMed

    Ahmad, Bashir; Rehman, Atta Ur; Malik, Sajid

    2016-01-01

    The north-western populations of Pakistan in the Federally Administered Tribal Areas (FATA) adjoining the Pakistan-Afghanistan border are an amalgamation of native and migrated Pashtun tribes. These tribal populations are in transition due to war conditions and geo-political turmoil on both sides of the border since the Soviet invasion in 1979. Bio-demographic and epidemiological data for these tribes are scarce. A prospective cross-sectional sample of 967 males was selected from a representative Pashtun population of Bajaur Agency, and information obtained on bio-demographic variables and marital union types. Analysis of these data revealed that consanguinity was 22.34% and the inbreeding coefficient F was calculated to be 0.0134. The inbreeding coefficient was observed to be higher in subjects who were illiterate, had unskilled jobs and who belonged to younger age categories, extended families and the Tarkalani tribe. Further analyses with respect to temporal variables like subject's age, year of marriage and age at marriage revealed that after a transition in marital union types in the early 80s, there has been a declining trend in the rate of consanguineous unions. Further, consanguineous unions in the parental generation were only 5%, but parental marriage types were predictors of subjects' marital union types. The data further establish that, contrary to a general notion about a high consanguinity rate in Pakistan, consanguineous unions are not common in Bajaur Agency and first cousin marriage is not the preferred type. Furthermore, this research shows that there is a great regional variation in the pattern of consanguinity in Pakistan that needs to be documented in order to draw a more comprehensive picture of the inbreeding coefficient in the country.

  20. New method for calculating a mathematical expression for streamflow recession

    USGS Publications Warehouse

    Rutledge, Albert T.

    1991-01-01

    An empirical method has been devised to calculate the master recession curve, which is a mathematical expression for streamflow recession during times of negligible direct runoff. The method is based on the assumption that the storage-delay factor, which is the time per log cycle of streamflow recession, varies linearly with the logarithm of streamflow. The resulting master recession curve can be nonlinear. The method can be executed by a computer program that reads a data file of daily mean streamflow, then allows the user to select several near-linear segments of streamflow recession. The storage-delay factor for each segment is one of the coefficients of the equation that results from linear least-squares regression. Using results for each recession segment, a mathematical expression of the storage-delay factor as a function of the log of streamflow is determined by linear least-squares regression. The master recession curve, which is a second-order polynomial expression for time as a function of log of streamflow, is then derived using the coefficients of this function.

  1. Recessions, Job Loss, and Mortality Among Older US Adults

    PubMed Central

    Beckfield, Jason

    2014-01-01

    Objectives. We analyzed how recessions and job loss jointly shape mortality risks among older US adults. Methods. We used data for 50 states from the Health and Retirement Study and selected individuals who were employed at ages 45 to 66 years during 1992 to 2011. We assessed whether job loss affects mortality risks, whether recessions moderate the effect of job loss on mortality, and whether individuals who do and do not experience job loss are differentially affected by recessions. Results. Compared with individuals not experiencing job loss, mortality risks among individuals losing their job in a recession were strongly elevated (hazard ratio = 1.6; 95% confidence interval = 1.1, 2.3). Job loss during normal times or booms is not associated with mortality. For employed workers, we found a reduction in mortality risks if local labor market conditions were depressed, but this result was not consistent across different model specifications. Conclusions. Recessions increase mortality risks among older US adults who experience job loss. Health professionals and policymakers should target resources to this group during recessions. Future research should clarify which health conditions are affected by job loss during recessions and whether access to health care following job loss moderates this relation. PMID:25211731

  2. A general geomorphological recession flow model for river basins

    NASA Astrophysics Data System (ADS)

    Biswal, Basudev; Nagesh Kumar, D.

    2013-08-01

    Recession flows in a basin are controlled by the temporal evolution of its active drainage network (ADN). The geomorphological recession flow model (GRFM) assumes that both the rate of flow generation per unit ADN length (q) and the speed at which ADN heads move downstream (c) remain constant during a recession event. Thereby, it connects the power law exponent of -dQ/dt versus Q (discharge at the outlet at time t) curve, α, with the structure of the drainage network, a fixed entity. In this study, we first reformulate the GRFM for Horton-Strahler networks and show that the geomorphic α (αg) is equal to D/>(D-1>), where D is the fractal dimension of the drainage network. We then propose a more general recession flow model by expressing both q and c as functions of Horton-Strahler stream order. We show that it is possible to have α =α g for a recession event even when q and c do not remain constant. The modified GRFM suggests that α is controlled by the spatial distribution of subsurface storage within the basin. By analyzing streamflow data from 39 U.S. Geological Survey basins, we show that α is having a power law relationship with recession curve peak, which indicates that the spatial distribution of subsurface storage varies across recession events.

  3. A mutation in SLC22A4 encoding an organic cation transporter expressed in the cochlea strial endothelium causes human recessive non-syndromic hearing loss DFNB60.

    PubMed

    Ben Said, Mariem; Grati, M'hamed; Ishimoto, Takahiro; Zou, Bing; Chakchouk, Imen; Ma, Qi; Yao, Qi; Hammami, Bouthaina; Yan, Denise; Mittal, Rahul; Nakamichi, Noritaka; Ghorbel, Abdelmonem; Neng, Lingling; Tekin, Mustafa; Shi, Xiao Rui; Kato, Yukio; Masmoudi, Saber; Lu, Zhongmin; Hmani, Mounira; Liu, Xuezhong

    2016-05-01

    The high prevalence/incidence of hearing loss (HL) in humans makes it the most common sensory defect. The majority of the cases are of genetic origin. Non-syndromic hereditary HL is extremely heterogeneous. Genetic approaches have been instrumental in deciphering genes that are crucial for auditory function. In this study, we first used NADf chip to exclude the implication of known North-African mutations in HL in a large consanguineous Tunisian family (FT13) affected by autosomal recessive non-syndromic HL (ARNSHL). We then performed genome-wide linkage analysis and assigned the deafness gene locus to ch:5q23.2-31.1, corresponding to the DFNB60 ARNSHL locus. Moreover, we performed whole exome sequencing on FT13 patient DNA and uncovered amino acid substitution p.Cys113Tyr in SLC22A4, a transporter of organic cations, cosegregating with HL in FT13 and therefore the cause of ARNSHL DFNB60. We also screened a cohort of small Tunisian HL families and uncovered an additional deaf proband of consanguineous parents that is homozygous for p.Cys113Tyr carried by the same microsatellite marker haplotype as in FT13, indicating that this mutation is ancestral. Using immunofluorescence, we found that Slc22a4 is expressed in stria vascularis (SV) endothelial cells of rodent cochlea and targets their apical plasma membrane. We also found Slc22a4 transcripts in our RNA-seq library from purified primary culture of mouse SV endothelial cells. Interestingly, p.Cys113Tyr mutation affects the trafficking of the transporter and severely alters ergothioneine uptake. We conclude that SLC22A4 is an organic cation transporter of the SV endothelium that is essential for hearing, and its mutation causes DFNB60 form of HL. PMID:27023905

  4. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    PubMed

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity).

  5. Awareness of folic acid for prevention of neural tube defects in a community with high prevalence of consanguineous marriages.

    PubMed

    Jaber, Lutfi; Karim, Igbaria A; Jawdat, Abu Moch; Fausi, Mawasi; Merlob, Paul

    2004-01-01

    Neural tube defects (NTDs) are severe congenital malformations and can be fatal. Intake of 0.4 mg folic in the periconceptional period reduces the risk of NTD by 50-70%. Consanguinity in the Arab population in Israel is a prevalent custom. The aim of this study was to assess the level of awareness regarding folic acid and its effect in the prevention of NTD among Arab Israeli women of childbearing age. We conducted a cross-sectional study. Of the 653 women (18-45 years) who were randomly selected for interview while visiting their family physician or well-baby clinic, 624 women completed the questionnaire. Fifty-three percent (n = 333) of the respondents had heard of folic acid; 14% (n = 89) were familiar with the protective effect of NTD and 3% (n = 18) had taken folic acid in the first months of pregnancy whereas none of them had used it in the preconception period. Highly educated women, women with one or two children, paramedics, and women of high socioeconomic status were more knowledgeable about the protective effects of folic acid (P < 0.001). Age and religion had no significant effect. An urgent need exists to improve the awareness of this population to the protective effect of folic acid. Daily supplementation and fertification of food with folic acid should be considered as the best way to improve the balance of folic acid in women of childbearing age of this special population (high prevalence of consanguinity). PMID:15050876

  6. An ABCD1 Mutation (c.253dupC) Caused Diverse Phenotypes of Adrenoleukodystrophy in an Iranian Consanguineous Pedigree

    PubMed Central

    Mehrpour, Masoud; Gohari, Faeze; Dizaji, Majid Zaki; Ahani, Ali; Malicdan, May Christine V.; Behnam, Babak

    2016-01-01

    Objectives Current study was the first to report a consanguineous Iranian pedigree with ABCD1 mutation. Methods Targeted molecular analysis was initially performed in three affected individuals in one family suspected to have X-ALD due to chronic progressive spasticity. Upon confirmation of genetic diagnosis, further neurologic and genetic evaluation of all family members was done. Results A mutation in ABCD1 was identified in 35 affected individuals (out 96 pedigree members). The c. 253dup, in exon 1, leads to a frame shift and a premature stop codon at amino acid position 194 (p.Arg85Profs*110). Surprisingly, affected individuals in our cohort show some variability in phenotype, including childhood cerebral ALD, adrenomyeloneuropathy, and addison-only disease phenotypes, expanding the phenotype of X-ALD with p.Arg85Profs*110. Conclusion This report characterizes the clinical spectrum of an expanded Iranian pedigree with X-ALD due to an ABCD1 mutation. Given a high frequency of carriers in this region, we expect the prevalence of X-ALD to be higher, underscoring the importance of genetic counseling through reliable identification of heterozygous as well as homozygote females in consanguineous communities. PMID:27489563

  7. Oculocutaneous albinism and consanguineous marriage among Spanish Gitanos or Calé--a study of 83 cases.

    PubMed

    Gamella, Juan F; Carrasco-Muñoz, Elisa Martín; Núñez Negrillo, Ana María

    2013-09-01

    This paper studies 83 cases of oculocutaneous albinism (OCA) in family networks of Gitanos in southeastern Spain, and analyzes their sustained inbreeding patterns and complex genealogical relationships. It is based in the family and genealogy reconstitution of the Gitano population of 22 contiguous localities using ethnographic and historical demography methods. The study found a prevalence of OCA among Gitanos in the area of about 1: 1,200. Most of the cases belong to three extended kin networks in which consanguineous marriages have been common for generations. In these networks there are other cases of visual and auditive congenital anomalies, and other birth defects such as brachydactily, polydactily, neurological defects, Potter Sequence, etc. In 61 OCA cases it was possible to trace inbreeding links with a depth of three to nine generations. For these cases the estimated alpha (average of the inbreeding coefficient, F) is 0.0222. Relationships between the parents of people affected are of three types: close, as between first or second cousins; distant, as between third or fourth cousins, and non-existent, as in mixed marriages. In most cases, however, persons with albinism are linked by multiple consanguineous links. Albinism seems to be a visible example of a high prevalence of birth defects in this minority, associated with founder effects, sustained inbreeding and high fertility rates. These conditions derive from Gitano's marriage preferences and pronatalist strategies. In turn, these strategies have to be related to the exclusion, persecution and segregation that Spanish Gypsies have suffered for centuries.

  8. Consanguinity and founder effect for Gaucher disease mutation G377S in a population from Tabuleiro do Norte, Northeastern Brazil.

    PubMed

    Chaves, R G; Pereira, L da Veiga; de Araújo, F T; Rozenberg, R; Carvalho, M D F; Coelho, J C; Michelin-Tirelli, K; Chaves, M de Freitas; Cavalcanti, G B

    2015-10-01

    Gaucher's disease (GD) is caused by a β-glucocerebrosidase deficiency, leading to the accumulation of glucocerebroside in the reticuloendothelial system. The prevalence of GD in Tabuleiro do Norte (TN) (1:4000) is the highest in Brazil. The purpose of this study was to present evidence of consanguinity and founder effect for the G377S mutation (c.1246G>A) among GD patients in TN based on enzyme, molecular and genealogical studies. Between March 2009 and December 2010, 131 subjects at risk for GD (GC in dried blood ≤2.19 nmol/h/ml) and 5 confirmed GD patients from the same community were submitted for molecular analysis to characterize the genetic profile of the population. Based on the enzymatic and molecular analysis, the subjects were classified into three categories: affected (n = 5), carrier (n = 20) and non-carrier (n = 111). All carriers were (G377S/wt). Affected subjects were homozygous (G377S/G377S). The identification of a single mutation in carriers and homozygotes from different generations, the history of the community and the genealogy study suggest that the high prevalence of GD in this population may be due to a combination of consanguinity and founder effect for the G377S mutation. PMID:25287185

  9. Surgical management of gingival recession: A clinical update

    PubMed Central

    Alghamdi, Hamdan; Babay, Nadir; Sukumaran, Anil

    2009-01-01

    Gingival recession is defined as the apical migration of the junctional epithelium with exposure of root surfaces. It is a common condition seen in both dentally aware populations and those with limited access to dental care. The etiology of the condition is multifactorial but is commonly associated with underlying alveolar morphology, tooth brushing, mechanical trauma and periodontal disease. Given the high rate of gingival recession defects among the general population, it is imperative that dental practitioners have an understanding of the etiology, complications and the management of the condition. The following review describes the surgical techniques to treat gingival recession. PMID:23960465

  10. Economic recession and headache-related hospital admissions.

    PubMed

    Chinta, Ravi; Rao, M B; Narendran, Vivek; Malla, Ganesh; Joshi, Hem

    2013-01-01

    Incidence of headaches across different regions and its relationship to unemployment rates in the United States before and during an economic recession was evaluated. Years 2008 and 2009 were determined as recessionary period. Headache-related admissions, particularly the uncomplicated headaches, increased significantly during recession. Proportion of women with headaches has increased and the age group of 25-54 years was the most affected during the recession. The hospital charges have increased even though the average length and charge of stay decreased. These findings are consistent with our understanding of effects of stress and unemployment on psychological and physical health.

  11. PREFACE: 3rd Italian-Pakistani Workshop on Relativistic Astrophysics (IPWRA2011)

    NASA Astrophysics Data System (ADS)

    De Paolis, Francesco; Siddiqui, Azad A.

    2012-03-01

    The Third Italian-Pakistani Workshop on Relativistic Astrophysics was held at the Rectorate of the University of Salento in Lecce on June 20-22, 2011. It follows the first two editions of this Workshop held at the Department of Physics of the University of Salento on 20-22 June 2007 and at ICRA (International Center for Relativistic Astrophysics) in Pescara on 8-10 July 2009. The Proceedings of the first two editions of this Workshop have been published in two special issues of Nuovo Cimento B [1] and General Relativity and Gravitation [2], respectively. The workshop series, whose aim is that of discussing the different aspects (both theoretical and observational) of Relativistic Astrophysics, follows the signature, in 2006, of an agreement between the University of Salento, Italy and the National University of Sciences and Technology (NUST), Pakistan, and aims at promoting scientific and academic cooperation between the parties. The organizing committee of this Workshop has decided to dedicate the present workshop's edition to the celebration of the 65th birthday of the founder of this series of meetings, Prof. Asghar Qadir, one of the greatest Pakistani scientists of any time and a renowned world expert in the theory of general relativity. Many of the Workshop's participants have either been students or collaborators of Asghar Qadir, or both. In Pakistan the words Relativity and Asghar Qadir are synonymous. It would not be entirely wrong to say that anybody who has anything to do with relativity in Pakistan is either his student or a student of one of his students. Asghar Qadir has inspired generations of researchers and teachers, and continues to be a source of inspiration for hard work and dedication. He is a mentor of Pakistani scientists and the equivalent in Pakistan of what John Archibald Wheeler has been in the US. Qadir and Wheeler An autographed picture of John Archibald Wheeler with a young Asghar Qadir Asghar had the rare privilege of being introduced

  12. Molecular mechanisms of autosomal recessive hypercholesterolemia.

    PubMed

    Wilund, Kenneth R; Yi, Ming; Campagna, Filomena; Arca, Marcello; Zuliani, Giovanni; Fellin, Renato; Ho, Yiu-Kee; Garcia, J Victor; Hobbs, Helen H; Cohen, Jonathan C

    2002-11-15

    Mutations in the phosphotyrosine-binding domain protein ARH cause autosomal recessive hypercholesterolemia (ARH), an inherited form of hypercholesterolemia due to a tissue-specific defect in the removal of low density lipoproteins (LDL) from the circulation. LDL uptake by the LDL receptor (LDLR) is markedly reduced in the liver but is normal or only moderately impaired in cultured fibroblasts of ARH patients. To define the molecular mechanism underlying ARH we examined ARH mRNA and protein in fibroblasts and lymphocytes from six probands with different ARH mutations. None of the probands had detectable full-length ARH protein in fibroblasts or lymphoblasts. Five probands were homozygous for mutations that introduced premature termination codons. No relationship was apparent between the site of the mutation in ARH and the amount of mRNA. The only mutation identified in the remaining proband was a SINE VNTR Alu (SVA) retroposon insertion in intron 1, which was associated with no detectable ARH mRNA. (125)I-LDL degradation was normal in ARH fibroblasts, as previously reported. In contrast, LDLR function was markedly reduced in ARH lymphoblasts, despite a 2-fold increase in LDL cell surface binding in these cells. These data indicate that all ARH mutations characterized to date preclude the synthesis of full-length ARH and that ARH is required for normal LDLR function in lymphocytes and hepatocytes, but not in fibroblasts. Residual LDLR function in cells that do not require ARH may explain why ARH patients have lower plasma LDL levels than do patients with homozygous familial hypercholesterolemia who have no functional LDLRs. PMID:12417523

  13. Frontal headache induced by osteoma of frontal recess.

    PubMed

    Kim, Kyung Soo

    2013-01-01

    We reported a case of osteoma involving the frontal recess, which presented as frontal headache and reviewed literatures. Also, this case highlights that sinunasal osteomas can cause pain by local mass effects, referred pain, or prostaglandin E2-mediated mechanisms.

  14. Chemical-mechanical polishing of recessed microelectromechanical devices

    DOEpatents

    Barron, Carole C.; Hetherington, Dale L.; Montague, Stephen

    1999-01-01

    A method is disclosed for micromachining recessed layers (e.g. sacrificial layers) of a microelectromechanical system (MEMS) device formed in a cavity etched into a semiconductor substrate. The method uses chemical-mechanical polishing (CMP) with a resilient polishing pad to locally planarize one or more of the recessed layers within the substrate cavity. Such local planarization using the method of the present invention is advantageous for improving the patterning of subsequently deposited layers, for eliminating mechanical interferences between functional elements (e.g. linkages) of the MEMS device, and for eliminating the formation of stringers. After the local planarization of one or more of the recessed layers, another CMP step can be provided for globally planarizing the semiconductor substrate to form a recessed MEMS device which can be integrated with electronic circuitry (e.g. CMOS, BiCMOS or bipolar circuitry) formed on the surface of the substrate.

  15. Chemical-mechanical polishing of recessed microelectromechanical devices

    DOEpatents

    Barron, C.C.; Hetherington, D.L.; Montague, S.

    1999-07-06

    A method is disclosed for micromachining recessed layers (e.g. sacrificial layers) of a microelectromechanical system (MEMS) device formed in a cavity etched into a semiconductor substrate. The method uses chemical-mechanical polishing (CMP) with a resilient polishing pad to locally planarize one or more of the recessed layers within the substrate cavity. Such local planarization using the method of the present invention is advantageous for improving the patterning of subsequently deposited layers, for eliminating mechanical interferences between functional elements (e.g. linkages) of the MEMS device, and for eliminating the formation of stringers. After the local planarization of one or more of the recessed layers, another CMP step can be provided for globally planarizing the semiconductor substrate to form a recessed MEMS device which can be integrated with electronic circuitry (e.g., CMOS, BiCMOS or bipolar circuitry) formed on the surface of the substrate. 23 figs.

  16. Recessed Downlights: A New Take on an Old Standby

    SciTech Connect

    Gordon, Kelly L.; McCullough, Jeffrey J.

    2004-01-02

    Recessed can downlights are a very popular form of lighting with many new homes containing 20 or more can lights. This trade magazine article describes PNNL's work with DOE's Emerging Technologies Program to promote energy-efficient recessed can downlights. PNNL manages the Recessed Can Downlights Project, which encourages manufacturers to produce energy-efficient recessed cans and tests them to verify that they have the following features: use pin-based CFL bulbs rated for 10,000 hours of life; use airtight housing to prevent air leakage into attics; are IC-rated for direct contact with insulation; have electronic ballasts for quiet, flicker-free operation; and have a min. light output of 900 initial lumens. Can lights that qualify are promoted through a DOE website. This is under DOE's Office of Energy Efficiency and Renewable Energy Building Technologies Program.

  17. Miniature paint-spray gun for recessed areas

    NASA Technical Reports Server (NTRS)

    Vanasse, M. A.

    1968-01-01

    Miniature spray gun regulates paints and other liquids to spray at close range, facilitating spraying of remote or recessed areas. Individual valves for regulating air pressure and paint maximizes atomization for low pressure spraying.

  18. 23. DETAIL OF TRELLIS BEAMS SHOWING RECESSED LIGHTING FIXTURES, WITH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    23. DETAIL OF TRELLIS BEAMS SHOWING RECESSED LIGHTING FIXTURES, WITH ONE BEAM CURVED TO FIT AROUND TRUNK OF FORMER TREE. - Fallingwater, State Route 381 (Stewart Township), Ohiopyle, Fayette County, PA

  19. Dropped-head in recessive oculopharyngeal muscular dystrophy.

    PubMed

    Garibaldi, Matteo; Pennisi, Elena Maria; Bruttini, Mirella; Bizzarri, Veronica; Bucci, Elisabetta; Morino, Stefania; Talerico, Caterina; Stoppacciaro, Antonella; Renieri, Alessandra; Antonini, Giovanni

    2015-11-01

    A 69-year-old woman presented a dropped head, caused by severe neck extensor weakness that had started two years before. She had also developed a mild degree of dysphagia, rhinolalia, eyelid ptosis and proximal limb weakness during the last months. EMG revealed myopathic changes. Muscle MRI detected fatty infiltration in the posterior neck muscles and tongue. Muscle biopsy revealed fiber size variations, sporadic rimmed vacuoles, small scattered angulated fibers and a patchy myofibrillar network. Genetic analysis revealed homozygous (GCN)11 expansions in the PABPN1 gene that were consistent with recessive oculopharyngeal muscular dystrophy (OPMD). There are a few reports of the recessive form, which has a later disease onset with milder symptoms and higher clinical variability than the typical dominantly inherited form. This patient, who is the first Italian and the eighth worldwide reported case of recessive OPMD, is also the first case of OPMD with dropped-head syndrome, which thus expands the clinical phenotype of recessive OPMD.

  20. Powered instrumentation in dissection of the frontal recess.

    PubMed

    Christmas, D A; Krouse, J H

    1996-06-01

    The use of powered instrumentation in functional endoscopic sinus surgery has become very popular due to its safety and thoroughness. An area which has been more problematic in the use of this technique has been the frontal recess, due to its anatomic location and associated risk of serious complications. We have done a number of powered dissections of the frontal recess as a surgical treatment of refractory frontal sinusitis, and find that it is extremely safe and effective. The ability of the powered devices to preserve normal mucosa allows an adequate surgical approach while significantly decreasing the postoperative risk of frontal recess stenosis and reocclusion. We feel that powered dissection of the frontal recess offers a significant advantage over standard techniques in this anatomic location.

  1. Gas insulated transmission line with insulators having field controlling recesses

    DOEpatents

    Cookson, Alan H.; Pederson, Bjorn O.

    1984-01-01

    A gas insulated transmission line having a novel insulator for supporting an inner conductor concentrically within an outer sheath. The insulator has a recess contiguous with the periphery of one of the outer and inner conductors. The recess is disposed to a depth equal to an optimum gap for the dielectric insulating fluid used for the high voltage insulation or alternately disposed to a large depth so as to reduce the field at the critical conductor/insulator interface.

  2. Production Recesses for Replaceable Cutting Inserts of Milling Tools

    NASA Astrophysics Data System (ADS)

    Kousal, Lukáš; Sadílek, Marek

    2014-12-01

    This article describes the production of recesses for replaceable cutting inserts of milling tools. The recess manufacture is exemplified on a D20 shanktype milling cutter with three replaceable cutting inserts. A new production technology and its operating cycle are demonstrated. A com-parison of the old and the new technologies shows the percentage saving of change cycles and used tools, including overall evaluation of the tech-nology.

  3. Experts offer differing views on the impact of a recession.

    PubMed

    Anderson, H J

    1990-12-01

    What are the risks of a prolonged recession for hospitals? Although health care would probably not be hurt as much as other industries by a lengthy downturn, financial experts are saying a continuation of the current soft economy would add to hospitals' already long list of financial woes. The coming recession "will exacerbate the problems for hospitals already facing fiscal stress," says Glenn Wagner, an investment banking consultant based in New York City. PMID:2242892

  4. Children's Physical Activity during Recess and Outside of School

    ERIC Educational Resources Information Center

    Beighle, Aaron; Morgan, Charles F.; Le Masurier, Guy; Pangrazi, Robert P.

    2006-01-01

    The purpose of this study was to examine children's physical activity during recess and outside of school. Third-, fourth-, and fifth-grade students (N = 270; 121 boys, age = 9.5 plus or minus 0.9 years; 150 girls, age = 9.6 plus or minus 0.9 years) wore sealed pedometers during a 15-minute recess period and outside of school for 4 consecutive…

  5. Remote Recession Sensing of Ablative Heat Shield Materials

    NASA Technical Reports Server (NTRS)

    Winter, Michael W.; Stackpoole, Margaret; Nawaz, Anuscheh; Gonzales, Gregory Lewis; Ho, Thanh

    2014-01-01

    Material recession and charring are two major processes determining the performance of ablative heat shield materials. Even in ground testing, the characterization of these two mechanisms relies on measurements of material thickness before and after testing, thus providing only information integrated over the test time. For recession measurements, optical methods such as imaging the sample surface during testing are under investigation but require high alignment and instrument effort, therefore being not established as a standard measurement method. For char depth measurements, the most common method so far consists in investigation of sectioned samples after testing or in the case of Stardust where core extractions were performed to determine char information. In flight, no reliable recession measurements are available, except total recession after recovering the heat shield on ground. Developments of mechanical recession sensors have been started but require substantial on board instrumentation adding mass and complexity. In this work, preliminary experiments to evaluate the feasibility of remote sensing of material recession and possibly char depth through optically observing the emission signatures of seeding materials in the post shock plasma is investigated. It is shown that this method can provide time resolved recession measurements without the necessity of accurate alignment procedures of the optical set-up and without any instrumentation on board of a spacecraft. Furthermore, recession data can be obtained without recovering flight hardware which would be a huge benefit for inexpensive heat shield material testing on board of small re-entry probes, e.g. on new micro-satellite re-entry probes as a possible future application of Cubesats or RBR

  6. A comparison of physical activity and sedentary behaviour in 9–11 year old British Pakistani and White British girls: a mixed methods study

    PubMed Central

    2014-01-01

    Background Previous studies suggest that British children of South Asian origin are less active and more sedentary than White British children. However, little is known about the behaviours underlying low activity levels, nor the familial contexts of active and sedentary behaviours in these groups. Our aim was to test hypotheses about differences between British Pakistani and White British girls using accelerometry and self-reports of key active and sedentary behaviours, and to obtain an understanding of factors affecting these behaviours using parental interviews. Methods Participants were 145 girls (70 White British and 75 British Pakistani) aged 9–11 years and parents of 19 of the girls. Accelerometry data were collected over 4 days and girls provided 24-hour physical activity interviews on 3 of these days. Multilevel linear regression models and generalised linear mixed models tested for ethnic differences in activity, sedentary time, and behaviours. Semi-structured interviews were conducted with parents. Results Compared to White British girls, British Pakistani girls accumulated 102 (95% CI 59, 145) fewer counts per minute and 14 minutes (95% CI 8, 20) less time in moderate to vigorous physical activity per day. British Pakistani girls spent more time (28 minutes per day, 95% CI 14, 42) sedentary. Fewer British Pakistani than White British girls reported participation in organised sports and exercise (OR 0.22 95% CI 0.08, 0.64) or in outdoor play (OR 0.42 95% CI 0.20, 0.91). Fewer British Pakistani girls travelled actively to school (OR 0.26 95% CI 0.10, 0.71). There was no significant difference in reported screen time (OR 0.88 95% CI 0.45, 1.73). Parental interviews suggested that structural constraints (e.g. busy family schedules) and parental concerns about safety were important influences on activity levels. Conclusions British Pakistani girls were less active than White British girls and were less likely to participate in key active behaviours

  7. Effects of a formal training programme on consanguineous marriages on high school students' knowledge and attitudes: an interventional study from Turkey.

    PubMed

    Kisioglu, Ahmet Nesimi; Ormeci, Ahmet Rifat; Uskun, Ersin; Ozturk, Mustafa; Ongel, Kurtulus

    2010-03-01

    Consanguineous marriage is traditionally common throughout the eastern Mediterranean region. Research has suggested that it is closely linked to the sociocultural and socioeconomical status of individuals, and education plays a critical role in decreasing the number of cases. This study aimed to determine the effects of a formal training programme on consanguineous marriages on the knowledge of, and attitudes towards, consanguineous marriage of high school students (n=804) in the Mediterranean region of Turkey. Seniors from three randomly selected public high schools participated in the pre-test and post-test design study. To determine the effects of the programme, students who received the training were compared with those who did not receive any formal training about the subject. After the post-tests were administered, data were collected and analysed using chi-squared and McNemar tests. The results showed significant differences in knowledge and attitudes among the students who had received the formal training programme and those who had not. In addition, the results indicated potential peer influence between the students who received training in consanguineous marriage and those who did not.

  8. Affinal and Consanguineal Kin as a Social Support for the Rural Elderly. Paper of the Journal Series of the North Carolina Agricultural Research Service, Raleigh, NC.

    ERIC Educational Resources Information Center

    Kivett, Vira R.

    Although the support network of elderly individuals has received increased attention recently, most research has focused on the parent child relationship without examining other levels of kin interrelations. To examine the help received by rural-transitional older adults from their consanguineous kin (adult children, grandchildren, siblings,…

  9. Recession curve analysis for groundwater levels: case study in Latvia

    NASA Astrophysics Data System (ADS)

    Gailuma, A.; VÄ«tola, I.; Abramenko, K.; Lauva, D.; Vircavs, V.; Veinbergs, A.; Dimanta, Z.

    2012-04-01

    Recession curve analysis is powerful and effective analysis technique in many research areas related with hydrogeology where observations have to be made, such as water filtration and absorption of moisture, irrigation and drainage, planning of hydroelectric power production and chemical leaching (elution of chemical substances) as well as in other areas. The analysis of the surface runoff hydrograph`s recession curves, which is performed to conceive the after-effects of interaction of precipitation and surface runoff, has approved in practice. The same method for analysis of hydrograph`s recession curves can be applied for the observations of the groundwater levels. There are manually prepared hydrograph for analysis of recession curves for observation wells (MG2, BG2 and AG1) in agricultural monitoring sites in Latvia. Within this study from the available monitoring data of groundwater levels were extracted data of declining periods, splitted by month. The drop-down curves were manually (by changing the date) moved together, until to find the best match, thereby obtaining monthly drop-down curves, representing each month separately. Monthly curves were combined and manually joined, for obtaining characterizing drop-down curves of the year for each well. Within the process of decreased recession curve analysis, from the initial curve was cut out upward areas, leaving only the drops of the curve, consequently, the curve is transformed more closely to the groundwater flow, trying to take out the impact of rain or drought periods from the curve. Respectively, the drop-down curve is part of the data, collected with hydrograph, where data with the discharge dominates, without considering impact of precipitation. Using the recession curve analysis theory, ready tool "A Visual Basic Spreadsheet Macro for Recession Curve Analysis" was used for selection of data and logarithmic functions matching (K. Posavec et.al., GROUND WATER 44, no. 5: 764-767, 2006), as well as

  10. The Effects of Different Recess Timing Regimens on Preschoolers' Classroom Attention

    ERIC Educational Resources Information Center

    Holmes, Robyn M.; Pellegrini, Anthony D.; Schmidt, Susan L.

    2006-01-01

    This study examined the effects of different recess timing regimens on preschoolers classroom attention. Using cognitive immaturity theory, we predicted that attention to a classroom task would be greater after a recess break. We also examined the extent to which different recess timing regimens related to post-recess attention. Participants were…

  11. Precarious Slopes? The Great Recession, Federal Stimulus, and New Jersey Schools. Working Paper #02-12

    ERIC Educational Resources Information Center

    Chakrabarti, Rajashri; Sutherland, Sarah

    2012-01-01

    While sparse literature exists investigating the impact of the Great Recession on various sectors of the economy, there is virtually no research that studies the effect of the Great Recession, or past recessions, on schools. This paper starts to fill the void. Studying school funding during the recession is of paramount importance because schools…

  12. Mutations in ALDH1A3 represent a frequent cause of microphthalmia/anophthalmia in consanguineous families.

    PubMed

    Abouzeid, Hana; Favez, Tatiana; Schmid, Angélique; Agosti, Céline; Youssef, Mohammed; Marzouk, Iman; El Shakankiry, Nihal; Bayoumi, Nader; Munier, Francis L; Schorderet, Daniel F

    2014-08-01

    Anophthalmia or microphthalmia (A/M), characterized by absent or small eye, can be unilateral or bilateral and represent developmental anomalies due to the mutations in several genes. Recently, mutations in aldehyde dehydrogenase family 1, member A3 (ALDH1A3) also known as retinaldehyde dehydrogenase 3, have been reported to cause A/M. Here, we screened a cohort of 75 patients with A/M and showed that mutations in ALDH1A3 occurred in six families. Based on this series, we estimate that mutations in ALDH1A3 represent a major cause of A/M in consanguineous families, and may be responsible for approximately 10% of the cases. Screening of this gene should be performed in a first line of investigation, together with SOX2.

  13. A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3

    PubMed Central

    Hassan, Muhammad Jawad; Santos, Regie Lyn P.; Rafiq, Muhammad Arshad; Chahrour, Maria H.; Pham, Thanh L.; Wajid, Muhammad; Hijab, Nadine; Wambangco, Michael; Lee, Kwanghyuk; Ansar, Muhammad; Yan, Kai; Ahmad, Wasim; Leal, Suzanne M.

    2010-01-01

    Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for ~75% of cases with a genetic etiology. A novel AR non-syndromic HI locus (DFNB47) was mapped to chromosome 2p25.1-p24.3, in two distantly related Pakistani kindreds. Genome scan and fine mapping were carried out using microsatellite markers. Multipoint linkage analysis resulted in a maximum LOD score of 4.7 at markers D2S1400 and D2S262. The three-unit support interval was bounded by D2S330 and D2S131. The region of homozygosity was found within the three-unit support interval and flanked by markers D2S2952 and D2S131, which corresponds to 13.2 cM according to the Rutgers combined linkage-physical map. This region contains 5.3 Mb according to the sequence-based physical map. Three candidate genes, KCNF1, ID2 and ATP6V1C2 were sequenced, and were found to be negative for functional sequence variants. PMID:16261342

  14. Management of the Spring Snowmelt Recession in Regulated Systems

    NASA Astrophysics Data System (ADS)

    Yarnell, S. M.; Lind, A.; Epke, G.; Viers, J. H.

    2013-12-01

    In unregulated rivers in the Sierra Nevada mountains of California, the spring snowmelt recession links high winter flows to low summer baseflow and is a consistent and predictable portion of the annual hydrograph. Consequently, it is an important resource to both riverine ecosystems and California's water supply. In regulated river systems where the spring snowmelt recession is often captured behind dams or diverted for hydropower, restoration of a more natural spring flow regime can provide distinct ecological benefits, such as breeding and migration cues for native species, increased habitat availability, and greater hydraulic habitat diversity. However, knowledge of how to create and manage an ecologically beneficial spring snowmelt recession in a regulated river system has been lacking. This study defined a methodology by which spring flow regimes can be modeled in regulated systems from the quantifiable characteristics of spring snowmelt recessions in unregulated rivers. Using fundamental flow components such as magnitude, timing, and rate of change, the spring snowmelt recession in eight unregulated rivers across the Sierra Nevada range was quantified to gain a better understanding of the predictability and variability across watersheds. The analysis found that unregulated Sierran systems behaved similarly with respect to seasonal patterns and flow recession shape (i.e., recession limb curvature), and thus flows could be modeled in a manner that mimics those predictable characteristics. Using this methodology that quantifies spring recession flows in terms of a daily percent decrease in flow, a series of flow recession scenarios were then created for application on a regulated Sierran river. Four scenarios, ranging from a slow natural recession to a short fast recession typically observed in regulated rivers following cessation of high flow spills, were evaluated within a 2D hydrodynamic model. The effects of the flows on suitable habitat for Foothill yellow

  15. Age-standardized Incidence Rates for Leukemia Associated with Consanguineous Marriages in 68 Countries, an Ecological Study.

    PubMed

    Saadat, Mostafa

    2015-01-01

    Consanguineous marriage that defines as a union between biologically related persons has a variety of known deleterious correlations with factors that affect public health within human populations. To investigate the association between the mean of inbreeding coefficient (α) and incidence of leukemia, the present ecological study on 68 countries was carried out. Statistical analysis showed that the age-standardized incidence rate of leukemia positively correlated with log10GNI per capita (r=0.699, df=66, P<0.001) and negatively correlated with log10α (r=-0.609, df=66, P<0.001). Controlling log10GNI per capita, a significant negative correlation between log10α and the age-standardized incidence rate of leukemia was observed (r=-0.392, df=65, P=0.001). The countries were stratified according to their annual GNI per capita, low and high-income countries with GNI per capita less than and more than 10,000$, respectively. Statistical analysis showed that in high-income countries, after controlling for log10GNI per capita, the correlation between the age-standardized incidence rate of leukemia and log10α was still significant (r=-0.600, df=36, P<0.001). It should be noted that there was no significant association between the age-standardized mortality rate due to leukemia and log10α (P>0.05). The present finding indicates that the rate of leukemia, age-standardized for incidence, is lower in countries with a high prevalence of consanguineous marriages.

  16. Clinical and descriptive genetic study of polydactyly: a Pakistani experience of 313 cases.

    PubMed

    Malik, S; Ullah, S; Afzal, M; Lal, K; Haque, S

    2014-05-01

    Polydactyly, a common hereditary condition with additional digits in hands and/or feet, is a very attractive model to appreciate clinical and genetic heterogeneity. In order to get an insight into its phenotypic manifestations, we ascertained a cohort of 313 independent families with polydactyly from Pakistan; 35% cases turned out to be familial while 65% were sporadic. In majority of the index cases, polydactyly was presented as an isolated digit defect. Preaxial polydactyly types were 48.24% and postaxial were 51.8%. Familial polydactylies mainly had bilateral and symmetrical presentations, whereas sporadic cases were mostly unilateral and less often symmetrical. In the 313 index subjects a total of 508 limbs with additional digits were recorded. Variable expression was evident as the involvement of upper limbs was more common than the lower, right hand than the left, and left foot than the right. The present cohort establishes interesting epidemiological attributes of polydactyly in the Pakistani population and highlights its extraordinary clinical heterogeneity. Molecular analyses of this cohort are anticipated to elucidate novel genetic factors involved in the origin of additional digits in the growing limb and may provide clues to the role of stochastic factors in the etiology of phenotypic variability in polydactyly.

  17. Perception of mental health in Pakistani nomads: An interpretative phenomenological analyses

    PubMed Central

    Choudhry, Fahad Riaz; Bokharey, Iram Zehra

    2013-01-01

    The study was conducted to explore the mental health issues of Pakistani nomads and to uncover their concept, ideation, and perception about mental health and illnesses. It was an exploratory study situated in the qualitative paradigm. The research strategy used was Interpretative Phenomenological Analysis (IPA), as the study was planned to explore the lived experiences of nomads regarding mental health and coping strategies and how they interpret those experiences. For data collection, focus group discussions (FGDs) were conducted. Seven participants were included in the FGDs, and two FGDs were conducted composed of both genders. The responses were recorded, and data were transcribed and analysed using IPA. Data verification procedures of peer review, which help to clarify researcher bias and rich thick description, were used. The major themes were lack of resources and myriad unfulfilled needs, specifically the basic needs (food, shelter, and drinking and bathing water). Moreover, a strong desire to fulfil the secondary needs of enjoyment and having luxuries was also reflected. A list of recommendations was forwarded for policy making of this marginalized community and to create awareness regarding mental health. PMID:24369779

  18. DNA damage in Pakistani pesticide-manufacturing workers assayed using the Comet assay.

    PubMed

    Bhalli, Javed A; Khan, Q M; Nasim, A

    2006-10-01

    The production and use of chemical pesticides has increased in recent years. Although the increased use of pesticides may benefit agriculture, they are also the potential source of environmental pollution, and exposure to pesticides can have negative consequences for human health. In the present study, we have assessed DNA damage in blood leukocytes from 29 Pakistani pesticide-factory workers and 35 controls of similar age and smoking history. The workers were exposed to various mixtures of organophosphates, carbamates, and pyrethroids. DNA damage was measured with the single cell gel electrophoresis (SCGE) assay or Comet assay, using the mean comet tail length (microm) as the DNA damage metric. Exposed workers had significantly longer comet tail lengths than the controls (mean +/- SD 19.98 +/- 2.87 vs. 7.38 +/- 1.48, P < 0.001). Of the possible confounding factors, smokers had significantly longer mean comet tail lengths than nonsmokers and exsmokers for both the workers (21.48 +/- 2.58 vs.18.37 +/- 2.28, P < 0.001) and the controls (8.86 +/- 0.56 vs. 6.79 +/- 1.31, P < 0.001), while age had a minimal effect on DNA damage (P > 0.05 and P < 0.05 for workers and controls, respectively). The results of this study indicate that occupational exposure to pesticides causes DNA damage. PMID:16917935

  19. Identification and functional characterization of natural human melanocortin 1 receptor mutant alleles in Pakistani population.

    PubMed

    Shahzad, Mohsin; Sires Campos, Julia; Tariq, Nabeela; Herraiz Serrano, Cecilia; Yousaf, Rizwan; Jiménez-Cervantes, Celia; Yousaf, Sairah; Waryah, Yar M; Dad, Haseeb A; Blue, Elizabeth M; Sobreira, Nara; López-Giráldez, Francesc; Kausar, Tasleem; Ali, Muhammad; Waryah, Ali M; Riazuddin, Saima; Shaikh, Rehan S; García-Borrón, José C; Ahmed, Zubair M

    2015-11-01

    Melanocortin 1 receptor (MC1R), a Gs protein-coupled receptor of the melanocyte's plasma membrane, is a major determinant of skin pigmentation and phototype. Upon activation by α-melanocyte stimulating hormone, MC1R triggers the cAMP cascade to stimulate eumelanogenesis. We used whole-exome sequencing to identify causative alleles in Pakistani families with skin and hair hypopigmentation. Six MC1R mutations segregated with the phenotype in seven families, including a p.Val174del in-frame deletion and a p.Tyr298* nonsense mutation, that were analyzed for function in heterologous HEK293 cells. p.Tyr298* MC1R showed no agonist-induced signaling to the cAMP or ERK pathways, nor detectable agonist binding. Conversely, signaling was comparable for p.Val174del and wild-type in HEK cells overexpressing the proteins, but binding analysis suggested impaired cell surface expression. Flow cytometry and confocal imaging studies revealed reduced plasma membrane expression of p.Val174del and p.Tyr298*. Therefore, p.Tyr298* was a total loss-of-function (LOF) allele, while p.Val174del displayed a partial LOF attribute.

  20. Association of interleukin-6 gene promoter polymorphism with coronary artery disease in Pakistani families.

    PubMed

    Satti, Humayoon Shafiq; Hussain, Sabir; Javed, Qamar

    2013-01-01

    Interleukin-6 (IL-6) is a well-known inflammatory cytokine and suggested to be involved in the development of coronary artery disease (CAD). IL-6 gene expression has been investigated with controversy in CAD patients. This study investigates the association of the IL-6 gene expression with CAD, the molecular basis for the regulation of interleukin-6 expression in a Pakistani population. Our data show that the serum IL-6 levels were increased in patients with CAD compared with healthy controls and that the IL-6 gene polymorphism at -174 was more prevalent in CAD cases. There was a statistically significant association between the IL-6 gene polymorphism and CAD, which may be associated with an increased risk for the disease. Moreover, circulating IL-6 and hs-CRP levels were significantly higher in patients with CC genotype (P < 0.0001 and P < 0.0001, resp.). In a binary logistic-regression model, an independent association was found between CAD and increased serum IL-6 and hs-CRP levels and -174G>C polymorphism. This is the first report on the IL-6 expression and the IL-6 gene polymorphism in patients with CAD from Pakistan, and hence it highlights a novel risk factor for the disease.

  1. Dietary patterns and their association with hypertension among Pakistani urban adults.

    PubMed

    Safdar, Nilofer F; Bertone-Johnson, Elizabeth R; Cordeiro, Lorraine; Jafar, Tazeen H; Cohen, Nancy L

    2015-01-01

    Hypertension is one of the most common chronic diseases affecting more than 25% of adults worldwide. In Pakistan, 33% of the adult population suffers from hypertension. Numerous epidemiological studies have demonstrated the critical role of dietary patterns in the causation, prevention and management of hypertension. There's a dearth of evidence from South Asia in this regard. The present study aimed to identify the association between dietary patterns and hypertension among 4304 low income urban adults who participated in the Control of Blood Pressure and Risk Attenuation (COBRA) study in Karachi, Pakistan. Dietary information was collected by a 33- item food frequency questionnaire and 3 unique dietary patterns namely; fat and sweet, fruit and vegetable, and seafood and yogurt patterns were derived using principal component factor analyses. We used univariate and multivariable logistic regression to examine the association between dietary patterns and hypertension. Men were more likely to have hypertension, while increase in age, and body mass index were also associated with hypertension (p<0.001). After adjusting for age, gender, education, marital status, body mass index, and tobacco use; the seafood and yogurt pattern was less likely (OR=0.78: 95% CI: 0.63, 0.98; p-value 0.03) to be associated with hypertension, whereas no significant associations were seen for other two dietary patterns. These findings suggest that certain dietary patterns may be associated with hypertension among Pakistani low income urban adults. PMID:26693757

  2. Iron status of the Pakistani population-current issues and strategies.

    PubMed

    Akhtar, Saeed; Ahmed, Anwaar; Ahmad, Asif; Ali, Zulfiqar; Riaz, Muhammad; Ismail, Tariq

    2013-01-01

    The present review aims to highlight the magnitude of iron status of Pakistani population and possible remedies to address iron deficiency among vulnerable groups. A computer-based search was carried out on "PubMed", "Google Search" and "Sciencedirect.com" to retrieve relevant scientific literature published in the last two decades. The search yielded 193 articles, of which 64 were culled and further screening was performed based on the type of vulnerable population groups, age, sex and pregnancy. A thorough review of current literature reveals that iron deficiency (ID) and iron deficiency anemia (IDA) widely persist in Pakistan and necessitate immediate remedial actions. Females of reproductive age and children under 5 years have been shown to be the most IDA affected population segment. Fortification of wheat flour has been suggested as the most viable approach aptly matching Pakistan's needs for combating IDA. The present review further stresses the need for global involvement to scale up efforts for mitigating ID and IDA to achieve Millennium Development Goals (MDGs) that are fundamentally based upon improving nutritional wellbeing of populations in developing economies by 2015.

  3. Psychological consequences of terrorist attacks: prevalence and predictors of mental health problems in Pakistani emergency responders.

    PubMed

    Razik, Saiqa; Ehring, Thomas; Emmelkamp, Paul M G

    2013-05-15

    Earlier research showing moderate to high prevalence rates of post-traumatic stress disorder (PTSD) and other mental health problems in emergency personnel has mostly been carried out in Western countries. Data from non-Western countries are largely lacking. The current study aimed to gather evidence on the prevalence of PTSD, anxiety, and depression in N=125 Pakistani emergency workers, most of whom (n=100; 80%) had been exposed to terrorist attacks. Fifteen percent of participants showed clinically relevant levels of PTSD, and 11-16% of participants reported heightened levels of anxiety or depression. Neither the experience of terrorist attacks per se nor the severity of the attack experienced was related to symptom severities. However, symptom levels of PTSD were related to a number of predictor variables, including subjective threat, peritraumatic dissociation, past traumas, rumination, and avoidant coping. Only a few variables were predictive of levels of anxiety and depression. In sum, a substantial subgroup of emergency workers experienced mental health problems, and prevalences were in the high range of those reported in earlier studies focusing on emergency personnel in Western countries.

  4. Iron status of the Pakistani population-current issues and strategies.

    PubMed

    Akhtar, Saeed; Ahmed, Anwaar; Ahmad, Asif; Ali, Zulfiqar; Riaz, Muhammad; Ismail, Tariq

    2013-01-01

    The present review aims to highlight the magnitude of iron status of Pakistani population and possible remedies to address iron deficiency among vulnerable groups. A computer-based search was carried out on "PubMed", "Google Search" and "Sciencedirect.com" to retrieve relevant scientific literature published in the last two decades. The search yielded 193 articles, of which 64 were culled and further screening was performed based on the type of vulnerable population groups, age, sex and pregnancy. A thorough review of current literature reveals that iron deficiency (ID) and iron deficiency anemia (IDA) widely persist in Pakistan and necessitate immediate remedial actions. Females of reproductive age and children under 5 years have been shown to be the most IDA affected population segment. Fortification of wheat flour has been suggested as the most viable approach aptly matching Pakistan's needs for combating IDA. The present review further stresses the need for global involvement to scale up efforts for mitigating ID and IDA to achieve Millennium Development Goals (MDGs) that are fundamentally based upon improving nutritional wellbeing of populations in developing economies by 2015. PMID:23945403

  5. Risk and reproductive decisions: British Pakistani couples’ responses to genetic counselling

    PubMed Central

    Shaw, Alison

    2011-01-01

    How far does ethnicity/culture/religion mediate couples’ responses to genetic risk? This paper examines the responses of 51 British Pakistani couples referred to a genetics clinic in southern England to counselling about recurrence risks for genetic problems in children. It is based on fieldwork conducted between 2000 and 2004 that combined participant observation of genetics consultations with interviews in respondents’ homes. Interviews were conducted with 62 adults in connection with these 51 cases, of which 32 were followed through two or more clinical consultations and 12 through more than one pregnancy. Risk responses were categorized as: taking the risk; postponing; exploring risk management or dismissing the risk as irrelevant to current circumstances. Responses were cross-referenced for associations with the severity of the condition, number of affected and unaffected children, availability of a prenatal test, age, gender, and migration history. I found that most couples were initially risk-takers who already had an unaffected child or children. Couples caring for living children with severe conditions were more likely to postpone. However, the risk responses of 15 couples changed over time, most towards and some away from risk management, reflecting changes in couples’ appreciation of the severity of the condition and their subsequent reproductive experiences. The study highlights the diversity and dynamism of responses within one ethnic group and challenges stereotypes about cultural and religious responses to genetic risk. PMID:21641705

  6. Chemical composition of particles from traditional burning of Pakistani wood species

    NASA Astrophysics Data System (ADS)

    Shahid, Imran; Kistler, Magdalena; Mukhtar, Azam; Ramirez-Santa Cruz, Carlos; Bauer, Heidi; Puxbaum, Hans

    2015-11-01

    Total particulate matter (TPM) emitted during burning of three types of Pakistani wood (eucalyptus camaldulensis, local name Safeeda; acacia nilotica, local name Kikar, Babul; dalbergia sissoo, Shisham, Tali) in a traditional brick stove were collected and analyzed for anhydrosugars, sugar alcohols, trace metals, soluble ions and carbonaceous species. This is a first study reporting anhydrosugars in wood smoke particles emitted during traditional burning of common wood types in Pakistan. Carbonaceous species showed the highest contribution to the particulate matter. Although the total carbon (TC) contribution was similar for all burnings (64.8-70.2%), the EC/OC ratio varied significantly, from 0.2 to 0.3 for Accacia and Dalbergia to 0.7-0.8 for Eucalyptus and Wood-mix. Among inorganic constituents potassium chloride and silicon were found at levels higher than 1%. The levoglucosan concentrations ranged from 3.0 to 6.6% (average 5.6%) with the highest value for Accacia and lowest value for the wood-mix. The high levoglucosan/mannosan ratios of 20-28 were typical for hardwood. The ratio between levoglucosan and galactosan varied stronger and was found to be around 13-20 for Accacia, Eucalyptus and Wood mix, and 43 for Dalbergia. The determined levoglucosan concentrations allowed assessing the conversion factor for calculation of biomass smoke contribution to ambient particulate matter levels in Pakistan.

  7. DNA damage in Pakistani pesticide-manufacturing workers assayed using the Comet assay.

    PubMed

    Bhalli, Javed A; Khan, Q M; Nasim, A

    2006-10-01

    The production and use of chemical pesticides has increased in recent years. Although the increased use of pesticides may benefit agriculture, they are also the potential source of environmental pollution, and exposure to pesticides can have negative consequences for human health. In the present study, we have assessed DNA damage in blood leukocytes from 29 Pakistani pesticide-factory workers and 35 controls of similar age and smoking history. The workers were exposed to various mixtures of organophosphates, carbamates, and pyrethroids. DNA damage was measured with the single cell gel electrophoresis (SCGE) assay or Comet assay, using the mean comet tail length (microm) as the DNA damage metric. Exposed workers had significantly longer comet tail lengths than the controls (mean +/- SD 19.98 +/- 2.87 vs. 7.38 +/- 1.48, P < 0.001). Of the possible confounding factors, smokers had significantly longer mean comet tail lengths than nonsmokers and exsmokers for both the workers (21.48 +/- 2.58 vs.18.37 +/- 2.28, P < 0.001) and the controls (8.86 +/- 0.56 vs. 6.79 +/- 1.31, P < 0.001), while age had a minimal effect on DNA damage (P > 0.05 and P < 0.05 for workers and controls, respectively). The results of this study indicate that occupational exposure to pesticides causes DNA damage.

  8. Polymorphism analysis of prion protein gene in 11 Pakistani goat breeds.

    PubMed

    Hassan, Mohammad Farooque; Khan, Sher Hayat; Babar, Masroor Ellahi; Yang, Lifeng; Ali, Tariq; Khan, Jamal Muhammad; Shah, Syed Zahid Ali; Zhou, Xiangmei; Hussain, Tanveer; Zhu, Ting; Hussain, Tariq; Zhao, Deming

    2016-07-01

    The association between caprine PrP gene polymorphisms and its susceptibility to scrapie has been investigated in current years. As the ORF of the PrP gene is extremely erratic in different breeds of goats, we studied the PrP gene polymorphisms in 80 goats which belong to 11 Pakistani indigenous goat breeds from all provinces of Pakistan. A total of 6 distinct polymorphic sites (one novel) with amino acid substitutions were identified in the PrP gene which includes 126 (A -> G), 304 (G -> T), 379 (A -> G), 414 (C -> T), 428 (A -> G) and 718 (C -> T). The locus c.428 was found highly polymorphic in all breeds as compare to other loci. On the basis of these PrP variants NJ phylogenetic tree was constructed through MEGA6.1 which showed that all goat breeds along with domestic sheep and Mauflon sheep appeared as in one clade and sharing its most recent common ancestors (MRCA) with deer species while Protein analysis has shown that these polymorphisms can lead to varied primary, secondary and tertiary structure of protein. Based on these polymorphic variants, genetic distance, multidimensional scaling plot and principal component analyses revealed the clear picture regarding greater number of substitutions in cattle PrP regions as compared to the small ruminant species. In particular these findings may pinpoint the fundamental control over the scrapie in Capra hircus on genetic basis. PMID:27388702

  9. Perception of mental health in Pakistani nomads: an interpretative phenomenological analyses.

    PubMed

    Choudhry, Fahad Riaz; Bokharey, Iram Zehra

    2013-01-01

    The study was conducted to explore the mental health issues of Pakistani nomads and to uncover their concept, ideation, and perception about mental health and illnesses. It was an exploratory study situated in the qualitative paradigm. The research strategy used was Interpretative Phenomenological Analysis (IPA), as the study was planned to explore the lived experiences of nomads regarding mental health and coping strategies and how they interpret those experiences. For data collection, focus group discussions (FGDs) were conducted. Seven participants were included in the FGDs, and two FGDs were conducted composed of both genders. The responses were recorded, and data were transcribed and analysed using IPA. Data verification procedures of peer review, which help to clarify researcher bias and rich thick description, were used. The major themes were lack of resources and myriad unfulfilled needs, specifically the basic needs (food, shelter, and drinking and bathing water). Moreover, a strong desire to fulfil the secondary needs of enjoyment and having luxuries was also reflected. A list of recommendations was forwarded for policy making of this marginalized community and to create awareness regarding mental health. PMID:24369779

  10. Perception of mental health in Pakistani nomads: an interpretative phenomenological analyses.

    PubMed

    Choudhry, Fahad Riaz; Bokharey, Iram Zehra

    2013-12-19

    The study was conducted to explore the mental health issues of Pakistani nomads and to uncover their concept, ideation, and perception about mental health and illnesses. It was an exploratory study situated in the qualitative paradigm. The research strategy used was Interpretative Phenomenological Analysis (IPA), as the study was planned to explore the lived experiences of nomads regarding mental health and coping strategies and how they interpret those experiences. For data collection, focus group discussions (FGDs) were conducted. Seven participants were included in the FGDs, and two FGDs were conducted composed of both genders. The responses were recorded, and data were transcribed and analysed using IPA. Data verification procedures of peer review, which help to clarify researcher bias and rich thick description, were used. The major themes were lack of resources and myriad unfulfilled needs, specifically the basic needs (food, shelter, and drinking and bathing water). Moreover, a strong desire to fulfil the secondary needs of enjoyment and having luxuries was also reflected. A list of recommendations was forwarded for policy making of this marginalized community and to create awareness regarding mental health.

  11. A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease.

    PubMed

    Mukarram, Osama; Akhtar, Naveed; Junaid, Ayesha; Mohyuddin, Aisha

    2016-07-01

    Aspirin is a key player in the management and prevention of stroke and myocardial infarction in patients with atherothrombosis. About 12% of Pakistanis suffering from coronary artery disease are resistant to aspirin's effects. Clinical, biochemical and genetic factors are known to be responsible for this phenomenon. We conducted this study to investigate whether previously studied polymorphisms in COX-1, GPIIIa, GPIa and P2RYI genes could be the cause of aspirin resistance in our population. Blood samples were collected from 29 aspirin non-responders and 60 ethnically matched responders. Aspirin response assay was performed on IMPACT-R and DNA prepared from blood using the phenol: chloroform method. Genotyping was carried out for four SNPS including COX-1 C50T (rs3842787), GPIIIA PIA1/A2 polymorphism (rs5918), GPIA C807T (rs1126643) and p2RY1 C893T (rs1065776). No statistically significant differences were observed in the allele or genotype frequencies between the aspirin non responders and responders indicating the possible involvement of different genetic determinants of aspirin resistance in our population. This study paves the way for further research into the field of aspirin resistance in Pakistan. PMID:27393450

  12. A study into the genetic basis of aspirin resistance in Pakistani patients with coronary artery disease.

    PubMed

    Mukarram, Osama; Akhtar, Naveed; Junaid, Ayesha; Mohyuddin, Aisha

    2016-07-01

    Aspirin is a key player in the management and prevention of stroke and myocardial infarction in patients with atherothrombosis. About 12% of Pakistanis suffering from coronary artery disease are resistant to aspirin's effects. Clinical, biochemical and genetic factors are known to be responsible for this phenomenon. We conducted this study to investigate whether previously studied polymorphisms in COX-1, GPIIIa, GPIa and P2RYI genes could be the cause of aspirin resistance in our population. Blood samples were collected from 29 aspirin non-responders and 60 ethnically matched responders. Aspirin response assay was performed on IMPACT-R and DNA prepared from blood using the phenol: chloroform method. Genotyping was carried out for four SNPS including COX-1 C50T (rs3842787), GPIIIA PIA1/A2 polymorphism (rs5918), GPIA C807T (rs1126643) and p2RY1 C893T (rs1065776). No statistically significant differences were observed in the allele or genotype frequencies between the aspirin non responders and responders indicating the possible involvement of different genetic determinants of aspirin resistance in our population. This study paves the way for further research into the field of aspirin resistance in Pakistan.

  13. Obstruction of adaptation in diploids by recessive, strongly deleterious alleles

    PubMed Central

    Assaf, Zoe June; Petrov, Dmitri A.; Blundell, Jamie R.

    2015-01-01

    Recessive deleterious mutations are common, causing many genetic disorders in humans and producing inbreeding depression in the majority of sexually reproducing diploids. The abundance of recessive deleterious mutations in natural populations suggests they are likely to be present on a chromosome when a new adaptive mutation occurs, yet the dynamics of recessive deleterious hitchhikers and their impact on adaptation remains poorly understood. Here we model how a recessive deleterious mutation impacts the fate of a genetically linked dominant beneficial mutation. The frequency trajectory of the adaptive mutation in this case is dramatically altered and results in what we have termed a “staggered sweep.” It is named for its three-phased trajectory: (i) Initially, the two linked mutations have a selective advantage while rare and will increase in frequency together, then (ii), at higher frequencies, the recessive hitchhiker is exposed to selection and can cause a balanced state via heterozygote advantage (the staggered phase), and (iii) finally, if recombination unlinks the two mutations, then the beneficial mutation can complete the sweep to fixation. Using both analytics and simulations, we show that strongly deleterious recessive mutations can substantially decrease the probability of fixation for nearby beneficial mutations, thus creating zones in the genome where adaptation is suppressed. These mutations can also significantly prolong the number of generations a beneficial mutation takes to sweep to fixation, and cause the genomic signature of selection to resemble that of soft or partial sweeps. We show that recessive deleterious variation could impact adaptation in humans and Drosophila. PMID:25941393

  14. Hypomorphic Mutations in PGAP2, Encoding a GPI-Anchor-Remodeling Protein, Cause Autosomal-Recessive Intellectual Disability

    PubMed Central

    Hansen, Lars; Tawamie, Hasan; Murakami, Yoshiko; Mang, Yuan; ur Rehman, Shoaib; Buchert, Rebecca; Schaffer, Stefanie; Muhammad, Safia; Bak, Mads; Nöthen, Markus M.; Bennett, Eric P.; Maeda, Yusuke; Aigner, Michael; Reis, André; Kinoshita, Taroh; Tommerup, Niels; Baig, Shahid Mahmood; Abou Jamra, Rami

    2013-01-01

    PGAP2 encodes a protein involved in remodeling the glycosylphosphatidylinositol (GPI) anchor in the Golgi apparatus. After synthesis in the endoplasmic reticulum (ER), GPI anchors are transferred to the proteins and are remodeled while transported through the Golgi to the cell membrane. Germline mutations in six genes (PIGA, PIGL, PIGM, PIGV, PIGN, and PIGO) in the ER-located part of the GPI-anchor-biosynthesis pathway have been reported, and all are associated with phenotypes extending from malformation and lethality to severe intellectual disability, epilepsy, minor dysmorphisms, and elevated alkaline phosphatase (ALP). We performed autozygosity mapping and ultra-deep sequencing followed by stringent filtering and identified two homozygous PGAP2 alterations, p.Tyr99Cys and p.Arg177Pro, in seven offspring with nonspecific autosomal-recessive intellectual disability from two consanguineous families. Rescue experiments with the altered proteins in PGAP2-deficient Chinese hamster ovary cell lines showed less expression of cell-surface GPI-anchored proteins DAF and CD59 than of the wild-type protein, substantiating the pathogenicity of the identified alterations. Furthermore, we observed a full rescue when we used strong promoters before the mutant cDNAs, suggesting a hypomorphic effect of the mutations. We report on alterations in the Golgi-located part of the GPI-anchor-biosynthesis pathway and extend the phenotypic spectrum of the GPI-anchor deficiencies to isolated intellectual disability with elevated ALP. GPI-anchor deficiencies can be interpreted within the concept of a disease family, and we propose that the severity of the phenotype is dependent on the location of the altered protein in the biosynthesis chain. PMID:23561846

  15. Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature.

    PubMed

    Abou Jamra, Rami; Philippe, Orianne; Raas-Rothschild, Annick; Eck, Sebastian H; Graf, Elisabeth; Buchert, Rebecca; Borck, Guntram; Ekici, Arif; Brockschmidt, Felix F; Nöthen, Markus M; Munnich, Arnold; Strom, Tim M; Reis, Andre; Colleaux, Laurence

    2011-06-10

    Intellectual disability inherited in an autosomal-recessive fashion represents an important fraction of severe cognitive-dysfunction disorders. Yet, the extreme heterogeneity of these conditions markedly hampers gene identification. Here, we report on eight affected individuals who were from three consanguineous families and presented with severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. Using a combination of autozygosity mapping and either Sanger sequencing of candidate genes or next-generation exome sequencing, we identified one mutation in each of three genes encoding adaptor protein complex 4 (AP4) subunits: a nonsense mutation in AP4S1 (NM_007077.3: c.124C>T, p.Arg42(∗)), a frameshift mutation in AP4B1 (NM_006594.2: c.487_488insTAT, p.Glu163_Ser739delinsVal), and a splice mutation in AP4E1 (NM_007347.3: c.542+1_542+4delGTAA, r.421_542del, p.Glu181Glyfs(∗)20). Adaptor protein complexes (AP1-4) are ubiquitously expressed, evolutionarily conserved heterotetrameric complexes that mediate different types of vesicle formation and the selection of cargo molecules for inclusion into these vesicles. Interestingly, two mutations affecting AP4M1 and AP4E1 have recently been found to cause cerebral palsy associated with severe intellectual disability. Combined with previous observations, these results support the hypothesis that AP4-complex-mediated trafficking plays a crucial role in brain development and functioning and demonstrate the existence of a clinically recognizable syndrome due to deficiency of the AP4 complex. PMID:21620353

  16. Alcohol and marijuana use while driving--an unexpected crash risk in Pakistani commercial drivers: a cross-sectional survey

    PubMed Central

    2012-01-01

    Background A significant proportion of road traffic crashes are attributable to alcohol and marijuana use while driving globally. Sale and use of both substances is illegal in Pakistan and is not considered a threat for road traffic injuries. However literature hints that this may not be the case. We did this study to assess usage of alcohol and marijuana in Pakistani commercial drivers. Methods A sample of 857 commercial bus and truck drivers was interviewed in October 2008 at the largest commercial vehicle station in Rawalpindi and Islamabad, Pakistan. Time location cluster sampling was used to select the subjects and a structured questionnaire was used to assess the basic demographic profile, substance abuse habits of the drivers while on the road, and reasons for usage of illicit substances while driving were recorded. Self reported information was collected after obtaining informed consent. Chi square and fisher exact tests were used to assess differences between groups and logistic regression was used to identify significant associations between driver characteristics and alcohol and marijuana use. Results Almost 10% of truck drivers use alcohol while driving on Pakistani roads. Marijuana use is almost 30% in some groups. Statistically different patterns of usage are seen between population subgroups based on age, ethnicity, education, and marital status. Regression analysis shows association of alcohol and marijuana use with road rage and error behaviours, and also with an increased risk of being involved in road crashes. The reported reasons for using alcohol or marijuana show a general lack of awareness of the hazardous nature of this practice among the commercial driver population. Conclusion Alcohol and marijuana use is highly prevalent in Pakistani commercial drivers. The issue needs to be recognized by concerned authorities and methods such as random breath tests and sobriety check points need to be employed for proper law enforcement. PMID:22369479

  17. The Great Recession and the risk for child maltreatment.

    PubMed

    Brooks-Gunn, Jeanne; Schneider, William; Waldfogel, Jane

    2013-10-01

    This study draws on the Fragile Families and Child Wellbeing Study (N=2,032), a birth cohort study of families with children from 20 U.S. cities. Interviews occurred between August 2007, and February 2010, when the children were approximately 9 years old. Macro-economic indicators of the Great Recession such as the Consumer Sentiment Index and unemployment and home foreclosure rates were matched to the data to estimate the links between different measures of the Great Recession and high frequency maternal spanking. We find that the large decline in consumer confidence during the Great Recession, as measured by the Consumer Sentiment Index, was associated with worse parenting behavior. In particular, lower levels of consumer confidence were associated with increased levels of high frequency spanking, a parenting behavior that is associated with greater likelihood of being contacted by child protective services. PMID:24045057

  18. Inferior oblique recession in thyroid-related orbitopathy.

    PubMed

    Salchow, Daniel J

    2015-06-01

    Thyroid-related orbitopathy is a form of orbital inflammation associated with thyroid dysfunction, developing in many patients with Graves disease. Fibrosis of the inferior rectus muscle can lead to restricted elevation and vertical ocular misalignment, which may be improved by recessing this muscle. In some patients, vertical misalignment persists after surgical weakening of one or more vertical rectus muscles. In this case series, unilateral inferior oblique recession as a secondary procedure after inferior rectus recession reduced hypertropia in primary gaze from 9(Δ) ± 3(Δ) to 1.3(Δ) ± 1.5(Δ) (mean ± standard deviation) and largest hypertropia in side gaze from 18.3 ± 2.1(Δ) to 3.3(Δ) ± 1.5(Δ). Postoperatively, all 3 patients were diplopia free in primary and downgaze. PMID:26059675

  19. Coastal cliff recession: the use of probabilistic prediction methods

    NASA Astrophysics Data System (ADS)

    Lee, E. M.; Hall, J. W.; Meadowcroft, I. C.

    2001-10-01

    A range of probabilistic methods is introduced for predicting coastal cliff recession, which provide a means of demonstrating the potential variability in such predictions. They form the basis for risk-based land-use planning, cliff management and engineering decision-making. Examples of probabilistic models are presented for a number of different cliff settings: the simulation of recession on eroding cliffs; the use of historical records and statistical experiments to model the behaviour of cliffs affected by rare, episodic landslide events; the adaptation of an event tree approach to assess the probability of failure of protected cliffs, taking into account the residual life of the existing defences; and the evaluation of the probability of landslide reactivation in areas of pre-existing landslide systems. These methods are based on a geomorphological assessment of the episodic nature of the recession process, together with historical records.

  20. The Great Recession and the Risk for Child Maltreatment

    PubMed Central

    Brooks-Gunn, Jeanne; Schneider, William; Waldfogel, Jane

    2013-01-01

    This study draws on the Fragile Families and Child Wellbeing Study (N = 2,032), a birth cohort study of families with children from 20 U.S. cities. Interviews occurred between August 2007, and February 2010, when the children were approximately 9 years old. Macro-economic indicators of the Great Recession such as the Consumer Sentiment Index and unemployment and home foreclosure rates were matched to the data to estimate the links between different measures of the Great Recession and high frequency maternal spanking. We find that the large decline in consumer confidence during the Great Recession, as measured by the Consumer Sentiment Index, was associated with worse parenting behavior. In particular, lower levels of consumer confidence were associated with increased levels of high frequency spanking, a parenting behavior that is associated with greater likelihood of being contacted by child protective services. PMID:24045057