Science.gov

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. Nonsense mutation in MERTK causes autosomal recessive retinitis pigmentosa in a consanguineous Pakistani family

    PubMed Central

    Shahzadi, Amber; Riazuddin, S Amer; Ali, Shahbaz; Li, David; Khan, Shaheen N; Husnain, Tayyab; Akram, Javed; Sieving, Paul A; Hejtmancik, J Fielding; Riazuddin, Sheikh

    2012-01-01

    Background Retinitis pigmentosa (RP) is one of the most common ophthalmic disorders affecting one in approximately 5000 people worldwide. A nuclear family was recruited from the Punjab province of Pakistan to study the genetic basis of autosomal recessive RP. Methods All affected individuals underwent a thorough ophthalmic examination and the disease was characterised based upon results for fundus photographs and electroretinogram recordings. Genomic DNA was extracted from peripheral leucocytes. Exclusion studies were performed with short tandem repeat (STR) markers flanking reported autosomal recessive RP loci. Haplotypes were constructed and results were statistically evaluated. Results The results of exclusion analyses suggested that family PKRP173 was linked to chromosome 2q harbouring mer tyrosine kinase protooncogene (MERTK), a gene previously associated with autosomal recessive RP. Additional STR markers refined the critical interval and placed it in a 13.4 cM (17 Mb) region flanked by D2S293 proximally and D2S347 distally. Significant logarithm of odds (LOD) scores of 3.2, 3.25 and 3.18 at θ=0 were obtained with markers D2S1896, D2S2269 and D2S160. Sequencing of the coding exons of MERTK identified a mutation, c.718G→T in exon 4, which results in a premature termination of p.E240X that segregates with the disease phenotype in the family. Conclusion Our results strongly suggest that the nonsense mutation in MERTK, leading to premature termination of the protein, is responsible for RP phenotype in the affected individuals of the Pakistani family. PMID:20538656

  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. PMID:24951542

  5. Mutations in GRM6 identified in consanguineous Pakistani families with congenital stationary night blindness

    PubMed Central

    Naeem, Muhammad Asif; Gottsch, Alexander D. H.; Ullah, Inayat; Khan, Shaheen N.; Husnain, Tayyab; Butt, Nadeem H.; Qazi, Zaheeruddin A.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2015-01-01

    Purpose This study was undertaken to investigate the causal mutations responsible for autosomal recessive congenital stationary night blindness (CSNB) in consanguineous Pakistani families. Methods Two consanguineous families with multiple individuals manifesting symptoms of stationary night blindness were recruited. Affected individuals underwent a detailed ophthalmological examination, including fundus examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion analyses were completed by genotyping closely spaced microsatellite markers, and two-point logarithm of odds (LOD) scores were calculated. All coding exons, along with the exon–intron boundaries of GRM6, were sequenced bidirectionally. Results According to the medical history available to us, affected individuals in both families had experienced night blindness from the early years of their lives. Fundus photographs of affected individuals in both the families appeared normal, with no signs of attenuated arteries or bone spicule pigmentation. The scotopic electroretinogram (ERG) response were absent in all of the affected individuals, while the photopic measurements show reduced b-waves. During exclusion analyses, both families localized to a region on chromosome 5q that harbors GRM6, a gene previously associated with autosomal recessive CSNB. Bidirectional sequencing of GRM6 identified homozygous single base pair changes, specifically c.1336C>T (p.R446X) and c.2267G>A (p.G756D) in families PKRP170 and PKRP172, respectively. Conclusions We identified a novel nonsense and a previously reported missense mutation in GRM6 that were responsible for autosomal recessive CSNB in patients of Pakistani decent. PMID:26628857

  6. Consanguinity related prenatal and postnatal mortality of the populations of seven Pakistani Punjab cities.

    PubMed Central

    Shami, S A; Schmitt, L H; Bittles, A H

    1989-01-01

    A retrospective study was conducted on prenatal and postnatal mortality among the populations of seven cities in the Pakistani province of Punjab. Consanguineous marriages were strongly favoured and the coefficients of inbreeding (F) for the present generation in each locality ranged from 0.0236 to 0.0286. There was a highly significant relationship between the degree of inbreeding and mortality, with most consanguinity related deaths reported in the neonatal, infantile, and childhood periods. The findings strongly suggest that consanguinity may play a major role in the high rates of postnatal mortality observed in Pakistani communities now resident in the United Kingdom. PMID:2716036

  7. Splice-site mutations identified in PDE6A responsible for retinitis pigmentosa in consanguineous Pakistani families

    PubMed Central

    Khan, Shahid Y.; Ali, Shahbaz; Naeem, Muhammad Asif; Khan, Shaheen N.; Husnain, Tayyab; Butt, Nadeem H.; Qazi, Zaheeruddin A.; Akram, Javed; Riazuddin, Sheikh; Ayyagari, Radha; Hejtmancik, J. Fielding

    2015-01-01

    Purpose This study was conducted to localize and identify causal mutations associated with autosomal recessive retinitis pigmentosa (RP) in consanguineous familial cases of Pakistani origin. Methods Ophthalmic examinations that included funduscopy and electroretinography (ERG) were performed to confirm the affectation status. Blood samples were collected from all participating individuals, and genomic DNA was extracted. A genome-wide scan was performed, and two-point logarithm of odds (LOD) scores were calculated. Sanger sequencing was performed to identify the causative variants. Subsequently, we performed whole exome sequencing to rule out the possibility of a second causal variant within the linkage interval. Sequence conservation was performed with alignment analyses of PDE6A orthologs, and in silico splicing analysis was completed with Human Splicing Finder version 2.4.1. Results A large multigenerational consanguineous family diagnosed with early-onset RP was ascertained. An ophthalmic clinical examination consisting of fundus photography and electroretinography confirmed the diagnosis of RP. A genome-wide scan was performed, and suggestive two-point LOD scores were observed with markers on chromosome 5q. Haplotype analyses identified the region; however, the region did not segregate with the disease phenotype in the family. Subsequently, we performed a second genome-wide scan that excluded the entire genome except the chromosome 5q region harboring PDE6A. Next-generation whole exome sequencing identified a splice acceptor site mutation in intron 16: c.2028–1G>A, which was completely conserved in PDE6A orthologs and was absent in ethnically matched 350 control chromosomes, the 1000 Genomes database, and the NHLBI Exome Sequencing Project. Subsequently, we investigated our entire cohort of RP familial cases and identified a second family who harbored a splice acceptor site mutation in intron 10: c.1408–2A>G. In silico analysis suggested that these

  8. 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

  9. Mutations in WDR62 gene in Pakistani families with autosomal recessive primary microcephaly

    PubMed Central

    2011-01-01

    Background Autosomal recessive primary microcephaly is a disorder of neurogenic mitosis that causes reduction in brain size. It is a rare heterogeneous condition with seven causative genes reported to date. Mutations in WD repeat protein 62 are associated with autosomal recessive primary microcephaly with cortical malformations. This study was initiated to screen WDR62 mutations in four consanguineous Pakistani families with autosomal recessive primary microcephaly. Methods As part of a large study to detect the genetic basis of primary microcephaly in Pakistan, homozygosity mapping and DNA sequencing was used to explore the genetic basis of autosomal recessive primary microcephaly in four families. Results Four out of 100 families recruited in the study revealed linkage to the MCPH2 locus on chromosome 19, which harbor WDR62 gene. DNA sequencing in these MCPH2 linked families result in the identification of a novel nonsense mutation (p.Q648X) and three previously known mutations. Conclusion Our data indicate that WDR62 mutations cause about 4% of autosomal recessive primary microcephaly in Pakistan. PMID:21961505

  10. In silico analysis of SIGMAR1 variant (rs4879809) segregating in a consanguineous Pakistani family showing amyotrophic lateral sclerosis without frontotemporal lobar dementia.

    PubMed

    Ullah, Muhammad Ikram; Ahmad, Arsalan; Raza, Syed Irfan; Amar, Ali; Ali, Amjad; Bhatti, Attya; John, Peter; Mohyuddin, Aisha; Ahmad, Wasim; Hassan, Muhammad Jawad

    2015-10-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting upper motor neurons in the brain and lower motor neurons in the brain stem and spinal cord, resulting in fatal paralysis. It has been found to be associated with frontotemporal lobar degeneration (FTLD). In the present study, we have described homozygosity mapping and gene sequencing in a consanguineous autosomal recessive Pakistani family showing non-juvenile ALS without signs of FTLD. Gene mapping was carried out in all recruited family members using microsatellite markers, and linkage was established with sigma non-opioid intracellular receptor 1 (SIGMAR1) gene at chromosome 9p13.2. Gene sequencing of SIGMAR1 revealed a novel 3'-UTR nucleotide variation c.672*31A>G (rs4879809) segregating with disease in this family. The C9ORF72 repeat region in intron 1, previously implicated in a related phenotype, was excluded through linkage, and further confirmation of exclusion was obtained by amplifying intron 1 of C9ORF72 with multiple primers in affected individuals and controls. In silico analysis was carried out to explore the possible role of 3'-UTR variant of SIGMAR1 in ALS. The Regulatory RNA motif and Element Finder program revealed disturbance in miRNA (hsa-miR-1205) binding site due to this variation. ESEFinder analysis showed new SRSF1 and SRSF1-IgM-BRCA1 binding sites with significant scores due to this variation. Our results indicate that the 3'-UTR SIGMAR1 variant c.672*31A>G may have a role in the pathogenesis of ALS in this family. PMID:26205306

  11. 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

  12. Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci.

    PubMed

    Najmabadi, Hossein; Motazacker, Mohammad Mahdi; Garshasbi, Masoud; Kahrizi, Kimia; Tzschach, Andreas; Chen, Wei; Behjati, Farkhondeh; Hadavi, Valeh; Nieh, Sahar Esmaeeli; Abedini, Seyedeh Sedigheh; Vazifehmand, Reza; Firouzabadi, Saghar Ghasemi; Jamali, Payman; Falah, Masoumeh; Seifati, Seyed Morteza; Grüters, Annette; Lenzner, Steffen; Jensen, Lars R; Rüschendorf, Franz; Kuss, Andreas W; Ropers, H Hilger

    2007-03-01

    Autosomal recessive gene defects are arguably the most important, but least studied genetic causes of severe cognitive dysfunction. Homozygosity mapping in 78 consanguineous Iranian families with nonsyndromic autosomal recessive mental retardation (NS-ARMR) has enabled us to determine the chromosomal localization of at least 8 novel gene loci for this condition. Our data suggest that in the Iranian population NS-ARMR is very heterogeneous, and they argue against the existence of frequent gene defects that account for more than a few percent of the cases. PMID:17120046

  13. Novel and recurrent AID mutations underlie prevalent autosomal recessive form of HIGM in consanguineous patients.

    PubMed

    Ouadani, Hanen; Ben-Mustapha, Imen; Ben-ali, Meriem; Ben-khemis, Leila; Larguèche, Beya; Boussoffara, Raoudha; Maalej, Sonia; Fetni, Ilhem; Hassayoun, Saida; Mahfoudh, Abdelmajid; Mellouli, Fethi; Yalaoui, Sadok; Masmoudi, Hatem; Bejaoui, Mohamed; Barbouche, Mohamed-Ridha

    2016-01-01

    Immunoglobulin class switch recombination deficiencies (Ig-CSR-D) are characterized by normal or elevated serum IgM level and absence of IgG, IgA, and IgE. Most reported cases are due to X-linked CD40L deficiency. Activation-induced cytidine deaminase deficiency is the most frequent autosomal recessive form, whereas CD40 deficiency is more rare. Herein, we present the first North African study on hyper IgM (HIGM) syndrome including 16 Tunisian patients. Phenotypic and genetic studies allowed us to determine their molecular basis. Three CD40LG mutations have been identified including two novels (c.348_351dup and c.782_*2del) and one already reported mutation (g.6182G>A). No mutation has been found in another patient despite the lack of CD40L expression. Interestingly, three AICDA mutations have been identified in 11 patients. Two mutations were novel (c.91T>C and c.389A>C found in one and five patients respectively), and one previously reported splicing mutation (c.156+1T>G) was found in five patients. Only one CD40-deficient patient, bearing a novel mutation (c.109T>G), has been identified. Thus, unlike previous reports, AID deficiency is the most frequent underlying molecular basis (68%) of Ig-CSR-D in Tunisian patients. This finding and the presence of specific recurrent mutations are probably due to the critical role played by inbreeding in North African populations. PMID:26545377

  14. STIL mutation causes autosomal recessive microcephalic lobar holoprosencephaly.

    PubMed

    Kakar, Naseebullah; Ahmad, Jamil; Morris-Rosendahl, Deborah J; Altmüller, Janine; Friedrich, Katrin; Barbi, Gotthold; Nürnberg, Peter; Kubisch, Christian; Dobyns, William B; Borck, Guntram

    2015-01-01

    Holoprosencephaly is a clinically and genetically heterogeneous midline brain malformation associated with neurologic manifestations including developmental delay, intellectual disability and seizures. Although mutations in the sonic hedgehog gene SHH and more than 10 other genes are known to cause holoprosencephaly, many patients remain without a molecular diagnosis. Here we show that a homozygous truncating mutation of STIL not only causes severe autosomal recessive microcephaly, but also lobar holoprosencephaly in an extended consanguineous Pakistani family. STIL mutations have previously been linked to centrosomal defects in primary microcephaly at the MCPH7 locus. Our results thus expand the clinical phenotypes associated with biallellic STIL mutations to include holoprosencephaly. PMID:25218063

  15. 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

  16. Consanguinity and mental retardation.

    PubMed

    Madhavan, T; Narayan, J

    1991-04-01

    Consanguinity among parents as a cause of mental retardation in their children is debatable. The present study was conducted to find out the effect of consanguinity on mental retardation where the causative factor is not established. A total of 517 mentally retarded persons and their families were studied out of which 160 were born of consanguineous marriage and 357 were of non-consanguineous marriage. The results indicated that, when there is a history of mental retardation in the family and if the parents are consanguineously married, the risk of mental retardation in the offspring is significantly high (chi 2 = 11.52; P less than 0.001). Among the consanguineously married families, the blood relationship of uncle-niece seems to have the highest risk of affecting the offsprings. The implications are discussed in detail. PMID:2072392

  17. A novel CHSY1 gene mutation underlies Temtamy preaxial brachydactyly syndrome in a Pakistani family.

    PubMed

    Sher, Gulab; Naeem, Muhammad

    2014-01-01

    Temtamy preaxial brachydactyly syndrome (TPBS) is an autosomal recessive rare disorder characterized by hyperphalangism of digits, facial dysmorphism, dental anomalies, sensorineural hearing loss, delayed motor and mental development, and growth retardation. Loss of function mutations have been recently reported in the CHSY1 gene to cause the TPBS. Here, we report a novel missense mutation (c.1897 G > A) in the CHSY1 gene in two TPBS patients from a consanguineous Pakistani family. The mutation predicted substitution of a highly conserved aspartate amino acid residue to asparagine at position 633 in the protein (D633N). Polyphen analysis supported the pathogenicity of D36N mutation. Our finding extends the body of recent evidence that supports the role of CHSY1 as a potential mediator of BMP signaling. PMID:24269551

  18. 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.

  19. 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

  20. Examining the family-centred approach to genetic testing and counselling among UK Pakistanis: a community perspective.

    PubMed

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

    2013-01-01

    WHO advice suggests a family-centred approach for managing the elevated risk of recessively inherited disorders in consanguineous communities, whilst emerging policy recommends community engagement as an integral component of genetic service development. This paper explores the feasibility of the family-centred approach in the UK Pakistani origin community. The study took place within a context of debate in the media, professional and lay circles about cousin marriage causing disability in children. Using qualitative methods, a total of six single-sex focus group discussions (n = 50) were conducted in three UK cities with a high settlement of people of Pakistani origin. Tape-recorded transcripts were analysed using framework analysis. Kinship networks within Pakistani origin communities are being sustained and marriage between close blood relatives continues to take place alongside other marriage options. Study participants were critical of what was perceived as a prevalent notion that cousin marriage causes disability in children. They were willing to discuss cousin marriage and disability, share genetic information and engage with genetic issues. A desire for accurate information and a public informed about genetic issues was articulated whilst ineffective communication of genetic risk information undermined professionals in their support role. This study suggests a community that is embracing change, one in which kinship networks are still active and genetic information exchange is taking place. At the community level, these are conditions supportive of the family-centred approach to genetic testing and counselling. PMID:23086468

  1. 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.

  2. 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

  3. A novel homozygous ISPD gene mutation causing phenotype variability in a consanguineous family.

    PubMed

    Baranello, Giovanni; Saredi, Simona; Sansanelli, Serena; Savadori, Paolo; Canioni, Eleonora; Chiapparini, Luisa; Balestri, Paolo; Malandrini, Alessandro; Arnoldi, Maria Teresa; Pantaleoni, Chiara; Morandi, Lucia; Mora, Marina

    2015-01-01

    Within the group of muscular dystrophies, dystroglycanopathies represent an important subgroup of recessively inherited disorders. Their severity varies from the relatively mild forms of adult-onset limb-girdle muscular dystrophy (LGMD), to the severe congenital muscular dystrophies (CMD) with cerebral and ocular involvement. We describe 2 consanguineous children of Pakistani origin, carrying a new homozygous missense mutation c.367G>A (p.Gly123Arg) in the ISPD gene. Mutations in this gene have been recently reported as a common cause of congenital and limb-girdle muscular dystrophy. Patient 1 is an 8-year-old female with an intermediate phenotype between CMD and early LGMD; patient 2 is a 20-month-old male and second cousin of patient 1, showing a CMD phenotype. Cognitive development, brain MRI, eye examination, electrocardiogram and echocardiogram were normal in both patients. To our knowledge, this is the first report on the co-occurrence of both a CMD/early LGMD intermediate phenotype and a CMD within the same family carrying a homozygous ISPD mutation. PMID:25444434

  4. Homozygous sequence variants in the FKBP10 gene underlie osteogenesis imperfecta in consanguineous families.

    PubMed

    Umair, Muhammad; Hassan, Annum; Jan, Abid; Ahmad, Farooq; Imran, Muhammad; Samman, Muhammad I; Basit, Sulman; Ahmad, Wasim

    2016-03-01

    Osteogenesis imperfecta (OI, MIM 610968) is a genetically and clinically heterogeneous disorder characterized by bone fragility. It is one of the rare forms of skeletal deformity caused by sequence variants in at least 14 different genes, including FKBP10 (MIM 607063) encoding protein FKBP65. Here we present three consanguineous families of Pakistani origin segregating OI in an autosomal-recessive pattern. Genotyping using either single-nucleotide polymorphism markers by Affymetrix GeneChip Human Mapping 250K Nsp array or polymorphic microsatellite markers revealed a homozygous region, containing a candidate gene FKBP10, among affected members on chromosome 17q21.2. Sequencing the FKBP10 gene revealed a homozygous novel nonsense variant (c.1490G>A, p.Trp497*) in the family A and two previously reported variants, including a missense (c.344G>A, p.Arg115Gln), in the family B and duplication of a nucleotide C (c.831dupC, p.Gly278ArgfsX295) in the family C. Our findings further extend the body of evidence that supports the importance of FKBP10 gene in the development of skeletal system. PMID:26538303

  5. Effects of parental consanguinity on mortality and reproductive function.

    PubMed

    Lindelius, R

    1980-01-01

    A study of consanguinity effects on mortality and fertility was performed. The original series consisted of families selected on the basis of the birth of at least one child with a congenital, monohybrid, autosomal recessive disease. Biologically related families were compared with unrelated ones, the latter group being used as a natural control group. The results are discussed. PMID:7358407

  6. A missense mutation (p.G274R) in gene ASPA causes Canavan disease in a Pakistani family.

    PubMed

    Hussain, Rashida; Daud, Shakeela; Kakar, Naseebullah; Ahmad, Adeel; Baloch, Abdul Hameed; Tareen, Abdul Malik; Kakar, Muhammad Azam; Ahmad, Jamil

    2012-05-01

    Canavan disease (OMIM 271900) is an autosomal recessive lethal neurodegenerative disorder characterized by spongy degeneration of the brain. A highly consanguineous Pakistani family with Canavan disease was enrolled on the basis of diagnosis. All the affected individuals have mental retardation, megalocephaly and degradation of motor skills, poor head control, partial vision loss, weakness of the muscles and raised urinary concentration of N-acetyl aspartic acid in the urine. Blood samples were collected from affected as well as normal siblings and processed for DNA purification. Linkage analysis was performed by typing three short tandem repeat markers D17S1583 (7.19 cM), D17S1828 (10.02 cM) and D17S919 (14.69 cM) for an already-reported gene/locus ASPA at chromosome 17p13.2 causing Canavan disease. During linkage analysis, all the affected individuals were homozygous for short tandem repeat markers while the normal siblings were heterozygous showing co-segregation of the disease. Gene ASPA (NM_000049) was undertaken to sequence for mutation analysis. As a result of sequence analysis, we found missense substitution 740A→G (p.G274R) in exon 6 of gene ASPA. To our knowledge, this is the first report about Canavan disease on a Pakistani family. PMID:22219087

  7. 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

  8. 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

  9. Effect of parental consanguinity on anthropometric measurements among the Sheikh Sunni Muslim boys of Delhi.

    PubMed

    Krishan, G

    1986-05-01

    The study of consanguineous marriage is an efficient way to elucidate the genetic structure of human populations. Such matings give an opportunity for recessive genes to manifest themselves by becoming homozygous. The present attempt examines the effects of parental consanguinity on various anthropometric measurements among the Sheikh Sunni Muslim boys of old Delhi between the ages of 11 and 16 years. A slight inbreeding depression has been observed for all eight anthropometric measurements, i.e., stature, span, sitting height, head length, head circumference, chest girth, and calf circumference. The results support earlier studies in regard to the effect of consanguinity on anthropometric measurements. PMID:3728657

  10. Recessive TBC1D24 Mutations Are Frequent in Moroccan Non-Syndromic Hearing Loss Pedigrees

    PubMed Central

    Bakhchane, Amina; Charif, Majida; Salime, Sara; Boulouiz, Redouane; Nahili, Halima; Roky, Rachida

    2015-01-01

    Mutations in the TBC1D24 gene are responsible for four neurological presentations: infantile epileptic encephalopathy, infantile myoclonic epilepsy, DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation and seizures) and NSHL (non-syndromic hearing loss). For the latter, two recessive (DFNB86) and one dominant (DFNA65) mutations have so far been identified in consanguineous Pakistani and European/Chinese families, respectively. Here we report the results of a genetic study performed on a large Moroccan cohort of deaf patients that identified three families with compound heterozygote mutations in TBC1D24. Four novel mutations were identified, among which, one c.641G>A (p.Arg214His) was present in the three families, and has a frequency of 2% in control Moroccan population with normal hearing, suggesting that it acts as an hypomorphic variant leading to restricted deafness when combined with another recessive severe mutation. Altogether, our results show that mutations in TBC1D24 gene are a frequent cause (>2%) of NSHL in Morocco, and that due to its possible compound heterozygote recessive transmission, this gene should be further considered and screened in other deaf cohorts. PMID:26371875

  11. 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

  12. 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

  13. 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

  14. Deficient T Cell Receptor Excision Circles (TRECs) in autosomal recessive hyper IgE syndrome caused by DOCK8 mutation: implications for pathogenesis and potential detection by newborn screening.

    PubMed

    Dasouki, Majed; Okonkwo, Kingsley C; Ray, Abhishek; Folmsbeel, Caspian K; Gozales, Diana; Keles, Sevgi; Puck, Jennifer M; Chatila, Talal

    2011-11-01

    Loss of function of DOCK8 is the major cause of autosomal recessive hyper IgE syndrome, a primary immunodeficiency with adaptive and innate immune dysfunction. Patients affected with ARHIES have atopic dermatitis and recurrent, potentially life-threatening viral and bacterial infections. Three consanguineous Pakistani siblings presented with severe atopic dermatitis and superinfection. Direct sequencing of DOCK8 in all three affected siblings demonstrated homozygosity for a deleterious, novel exon 14 frame shift mutation. Current newborn screening for severe combined immunodeficiency syndrome (SCID) and related T cell disorders relies on the quantitation of T Cell Receptor Excision Cells (TRECs) in dried blood spots (DBS). Significantly, both older affected siblings had undetectable TRECs, and TREC copy number was reduced in the youngest sibling. These findings suggest that AR-HIES may be detected by TREC newborn screening, and this diagnosis should be considered in the evaluation of newborns with abnormal TRECs who do not have typical SCID. PMID:21763205

  15. 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

  16. Mutations in the Beta Propeller WDR72 Cause Autosomal-Recessive Hypomaturation Amelogenesis Imperfecta

    PubMed Central

    El-Sayed, Walid; Parry, David A.; Shore, Roger C.; Ahmed, Mushtaq; Jafri, Hussain; Rashid, Yasmin; Al-Bahlani, Suhaila; Al Harasi, Sharifa; Kirkham, Jennifer; Inglehearn, Chris F.; Mighell, Alan J.

    2009-01-01

    Healthy dental enamel is the hardest and most highly mineralized human tissue. Though acellular, nonvital, and without capacity for turnover or repair, it can nevertheless last a lifetime. Amelogenesis imperfecta (AI) is a collective term for failure of normal enamel development, covering diverse clinical phenotypes that typically show Mendelian inheritance patterns. One subset, known as hypomaturation AI, is characterised by near-normal volumes of organic enamel matrix but with weak, creamy-brown opaque enamel that fails prematurely after tooth eruption. Mutations in genes critical to enamel matrix formation have been documented, but current understanding of other key events in enamel biomineralization is limited. We investigated autosomal-recessive hypomaturation AI in a consanguineous Pakistani family. A whole-genome SNP autozygosity screen identified a locus on chromosome 15q21.3. Sequencing candidate genes revealed a point mutation in the poorly characterized WDR72 gene. Screening of WDR72 in a panel of nine additional hypomaturation AI families revealed the same mutation in a second, apparently unrelated, Pakistani family and two further nonsense mutations in Omani families. Immunohistochemistry confirmed intracellular localization in maturation-stage ameloblasts. WDR72 function is unknown, but as a putative β propeller is expected to be a scaffold for protein-protein interactions. The nearest homolog, WDR7, is involved in vesicle mobilization and Ca2+-dependent exocytosis at synapses. Vesicle trafficking is important in maturation-stage ameloblasts with respect to secretion into immature enamel and removal of cleaved enamel matrix proteins via endocytosis. This raises the intriguing possibility that WDR72 is critical to ameloblast vesicle turnover during enamel maturation. PMID:19853237

  17. Consanguinity among the Saudi Arabian population.

    PubMed Central

    el-Hazmi, M A; al-Swailem, A R; Warsy, A S; al-Swailem, A M; Sulaimani, R; al-Meshari, A A

    1995-01-01

    This study was conducted on 3212 Saudi families to investigate the prevalence of consanguineous marriages. The families were interviewed and the information on the relationship between the husband and wife was obtained. The overall rate of consanguinity shows that 57.7% of the families screened were consanguineous. The most frequent were first cousin marriages (28.4%) followed by distant relative marriages (15.2%) and second cousin marriages (14.6%). The families were grouped according to the province of their origin and the consanguinity rates were calculated accordingly. There were slight differences in the consanguinity rates in the five provinces, which ranged from 52.1% to 67.7%. In each province first cousin marriages were the most frequently encountered pattern, ranging from 17.9% to 40.9%. The inbreeding coefficient (F) was calculated for each province and ranged from 0.020 to 0.030. Within each province, there were several significant differences among the populations in the different areas. The highest rate of consanguinity was 80.6% in Samtah and the lowest rate was around 34% in Abha in the South Western province. These results place Saudi Arabia among the countries of the world with a high rate of consanguinity. The possible consequences of increased consanguinity are presented and discussed. PMID:7473654

  18. Frequent detection of parental consanguinity in children with developmental disorders by a combined CGH and SNP microarray

    PubMed Central

    2013-01-01

    Background Genomic microarrays have been used as the first-tier cytogenetic diagnostic test for patients with developmental delay/intellectual disability, autism spectrum disorders and/or multiple congenital anomalies. The use of SNP arrays has revealed regions of homozygosity in the genome which can lead to identification of uniparental disomy and parental consanguinity in addition to copy number variations. Consanguinity is associated with an increased risk of birth defects and autosomal recessive disorders. However, the frequency of parental consanguinity in children with developmental disabilities is unknown, and consanguineous couples may not be identified during doctor’s visit or genetic counseling without microarray. Results We studied 607 proband pediatric patients referred for developmental disorders using a 4 × 180 K array containing both CGH and SNP probes. Using 720, 360, 180, and 90 Mb as the expected sizes of homozygosity for an estimated coefficient of inbreeding (F) 1/4, 1/8, 1/16, 1/32, parental consanguinity was detected in 21cases (3.46%). Conclusion Parental consanguinity is not uncommon in children with developmental problems in our study population, and can be identified by use of a combined CGH and SNP chromosome microarray. Identification of parental consanguinity in such cases can be important for further diagnostic testing. PMID:24053112

  19. 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

  20. 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

  1. 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

  2. Single Nucleotide Polymorphism (SNP) Arrays and Unexpected Consanguinity: Considerations for Clinicians When Returning Results to Families

    PubMed Central

    Delgado, Fernanda; Tabor, Holly K.; Chow, Penny M.; Conta, Jessie H.; Feldman, Kenneth W.; Tsuchiya, Karen D.; Beck, Anita E.

    2014-01-01

    Purpose The broad use of SNP microarrays has increased identification of unexpected consanguinity. Therefore, guidelines to address reporting of consanguinity have been published for clinical laboratories. Because no such guidelines exist for clinicians, we describe a case and present recommendations for clinicians to disclose unexpected consanguinity to families. Methods In a boy with multiple endocrine abnormalities and structural birth defects, SNP array analysis revealed ~23% autosomal homozygosity suggestive of a 1st-degree parental relationship. We assembled an interdisciplinary healthcare team, planned the most appropriate way to discuss results of the SNP array with the adult mother including the possibility of multiple autosomal recessive disorders in her child, and finally met with her as a team. Results From these discussions, we developed four major considerations for clinicians returning results of unexpected consanguinity, all guided by the child’s best interests: 1) ethical and legal obligations for reporting possible abuse, 2) preservation of the clinical relationship, 3) attention to justice and psychosocial challenges, and 4) utilization of the SNP array results to guide further testing. Conclusion As SNP arrays become a common clinical diagnostic tool, clinicians can use this framework to return results of unexpected consanguinity to families in a supportive and productive manner. PMID:25232848

  3. 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

  4. 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.

  5. Mutations in patients with osteogenesis imperfecta from consanguineous Indian families.

    PubMed

    Stephen, Joshi; Girisha, Katta Mohan; Dalal, Ashwin; Shukla, Anju; Shah, Hitesh; Srivastava, Priyanka; Kornak, Uwe; Phadke, Shubha R

    2015-01-01

    Osteogenesis imperfecta (OI) is a spectrum of genetic disorders with decreased bone density and bone fragility. Most of the cases of OI are inherited in autosomal dominant fashion with mutations in COL1A1 or COL1A2 genes. Over last few years, twelve genes for autosomal recessive OI have been identified. In this study we have evaluated seven patients with OI from consanguineous Indian families. Homozygosity mapping using SNP microarray was done and selected candidate genes were sequenced. Candidate genes were identified in four out of seven patients studied. Four mutations, namely; a homozygous non-sense (p.Q178*) and a deletion (p.F277del) mutations in SERPINF1 gene, a missense mutation (p.M101K) in PPIB gene and a nonsense mutation (p.E45*) in CRTAP gene were identified. In three patients for whom the regions of homozygosity did not reveal any known autosomal recessive OI genes, exome sequencing was performed and we identified a known missense mutation (p.G1012S) in COL1A2 gene in one of the patients. As WNT1 gene was not properly covered in exome sequencing in one patient, the gene was sequenced and a homozygous in-frame deletion of four amino acids (p.Phe176_Leu179del) was identified. In one of the three cases the exome sequencing did not reveal a mutation in any known OI genes, suggesting the possibility of mutations in an unidentified gene. The phenotypes of all the cases are described. This work proves the power of homozygosity mapping followed by candidate gene sequencing approach for clinical application in consanguineous families. PMID:25450603

  6. Homozygosity mapping reveals mutations of GRXCR1 as a cause of autosomal-recessive nonsyndromic hearing impairment.

    PubMed

    Schraders, Margit; Lee, Kwanghyuk; Oostrik, Jaap; Huygen, Patrick L M; Ali, Ghazanfar; Hoefsloot, Lies H; Veltman, Joris A; Cremers, Frans P M; Basit, Sulman; Ansar, Muhammad; Cremers, Cor W R J; Kunst, Henricus P M; Ahmad, Wasim; Admiraal, Ronald J C; Leal, Suzanne M; Kremer, Hannie

    2010-02-12

    We identified overlapping homozygous regions within the DFNB25 locus in two Dutch and ten Pakistani families with sensorineural autosomal-recessive nonsyndromic hearing impairment (arNSHI). Only one of the families, W98-053, was not consanguineous, and its sibship pointed toward a reduced critical region of 0.9 Mb. This region contained the GRXCR1 gene, and the orthologous mouse gene was described to be mutated in the pirouette (pi) mutant with resulting hearing loss and circling behavior. Sequence analysis of the GRXCR1 gene in hearing-impaired family members revealed splice-site mutations in two Dutch families and a missense and nonsense mutation, respectively, in two Pakistani families. The splice-site mutations are predicted to cause frameshifts and premature stop codons. In family W98-053, this could be confirmed by cDNA analysis. GRXCR1 is predicted to contain a GRX-like domain. GRX domains are involved in reversible S-glutathionylation of proteins and thereby in the modulation of activity and/or localization of these proteins. The missense mutation is located in this domain, whereas the nonsense and splice-site mutations may result in complete or partial absence of the GRX-like domain or of the complete protein. Hearing loss in patients with GRXCR1 mutations is congenital and is moderate to profound. Progression of the hearing loss was observed in family W98-053. Vestibular dysfunction was observed in some but not all affected individuals. Quantitative analysis of GRXCR1 transcripts in fetal and adult human tissues revealed a preferential expression of the gene in fetal cochlea, which may explain the nonsyndromic nature of the hearing impairment. PMID:20137778

  7. 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

  8. Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum

    PubMed Central

    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

  9. 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

  10. 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

  11. Autosomal recessive osteopetrosis in Arab children.

    PubMed

    Abdel-Al, Y K; Shabani, I S; Lubani, M M; al-Ghawabi, M A; Ibrahim, M D; al-Mohtaseb, S; Duodin, K I

    1994-01-01

    Nineteen Arab children including six boys and 13 girls in ten sibships were diagnosed as having osteopetrosis over a 5-year period in various hospitals in Kuwait. Eighteen patients had an isolated autosomal recessive form and one had autosomal recessive osteopetrosis associated with renal tubular acidosis. The mean age of diagnosis was 24 months. Parental consanguinity was high amongst them (68%). Anaemia, hepatosplenomegaly, failure to thrive, recurrent infections and neurological manifestations were common. Associated congenital abnormalities were found in 26%. Deafness, hydrocephalus and dental caries were relatively less common. A high mortality (37%) owing to infection was noted. The medical management and recommendations for patient care are discussed briefly. PMID:7516136

  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. 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. PMID:12346200

  14. 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

  15. 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

  16. Azygoesophageal recess.

    PubMed

    Ravenel, James G; Erasmus, Jeremy J

    2002-07-01

    Knowledge of the normal radiologic appearance and manifestations of disease in the azygoesophageal recess can facilitate the detection and diagnosis of intrathoracic disease. The azygoesophageal recess is located lateral or posterior to the esophagus and anterior to the spine. It extends from the anterior turn of the azygous vein to the aortic hiatus. The configuration of the azygoesophageal recess is normally a smooth arc convex to the left. Because the right lung extends into the recess, pathology in this region can often be detected radiographically and typically manifests as increased opacity and/or as a contour abnormality. In adults, convexity directed to the right and immediately below the level of the azygous vein on a frontal radiograph is abnormal and requires further evaluation. PMID:12082374

  17. Consanguinity and hereditary hearing loss in Qatar.

    PubMed

    Girotto, Giorgia; Mezzavilla, Massimo; Abdulhadi, Khalid; Vuckovic, Dragana; Vozzi, Diego; Khalifa Alkowari, Moza; Gasparini, Paolo; Badii, Ramin

    2014-01-01

    Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins. Thus, there is a higher risk for most inherited diseases including hereditary hearing loss (HHL). In particular, a hearing loss prevalence of 5.2% has been reported in Qatar, with parental consanguinity being more common among affected individuals as compared with unaffected ones. Our recent molecular results confirm a high homogeneity and level of inbreeding in Qatari HHL patients. Among all HHL genes, GJB2, the major player worldwide, accounts for a minor proportion of cases and at least 3 additional genes have been found to be mutated in Qatari patients. Interestingly, one gene, BDP1, has been described to cause HHL only in this country. These results point towards an unexpected level of genetic heterogeneity despite the high level of inbreeding. This review provides an up-to-date picture of HHL in Qatar and of the impact of consanguinity on this disease. PMID:25060281

  18. 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.

  19. Epidemiology, major risk factors and genetic predisposition for breast cancer in the Pakistani population.

    PubMed

    Shaukat, Uzma; Ismail, Muhammad; Mehmood, Nasir

    2013-01-01

    Occurrence of breast cancer is related to genetic as well as cultural, environmental and life-style factors. Variations in diversity of these factors among different ethnic groups and geographical areas emphasize the immense need for studies in all racial-ethnic populations. The incidence of breast cancer in Pakistan is highest in Asians after Jews in Israel and 2.5 times higher than that in neighboring countries like Iran and India, accounting for 34.6% of female cancers. The Pakistani population is deficient in information regarding breast cancer etiology and epidemiology, but efforts done so far had suggested consanguinity as a major risk factor for frequent mutations leading to breast cancer and has also shed light on genetic origins in different ethnic groups within Pakistan. World-wide research efforts on different ethnicities have enhanced our understanding of genetic predisposition to breast cancer but despite these discoveries, 75% of the familial risk of breast cancer remains unexplained, highlighting the fact that the majority of breast cancer susceptibility genes remain unidentified. For this purpose Pakistani population provides a strong genetic pool to elucidate the genetic etiology of breast cancer because of cousin marriages. In this review, we describe the known breast cancer predisposition factors found in the local Pakistani population and the epidemiological research work done to emphasize the importance of exploring factors/variants contributing to breast cance, in order to prevent, cure and decrease its incidence in our country. PMID:24289553

  20. Sex-linked recessive

    MedlinePlus

    Inheritance - sex-linked recessive; Genetics - sex-linked recessive; X-linked recessive ... X-linked recessive diseases usually occur in males. Males have only one X chromosome. A single recessive ...

  1. Chromosome abnormality rate among Iranian patients with idiopathic mental retardation from consanguineous marriages

    PubMed Central

    Behjati, Farkhondeh; Ghasemi Firouzabadi, Saghar; Kahrizi, Kimia; Kariminejad, Roxana; Bagherizadeh, Iman; Ansari, Javad; Fallah, Masoumeh; Mojtahedi, Forough; Darvish, Hossein; Bahrami Monajemi, Gholamreza; Abedini, S. Sedigheh; Jamali, Payman; Mojahedi, Faezeh; Zadeh-Vakili, Azita; Najmabadi, Hossein

    2011-01-01

    Introduction Mental retardation (MR) has heterogeneous aetiology mostly with genetic causes. Chromosomal aberrations are one of the most common causes of MR. Reports on chromosome abnormality rate among consanguineous families are sparse. In order to identify the chromosome abnormality rate in idiopathic mental retardation from consanguineous marriages, a total of 322 Iranian families with positive family history for MR were investigated in the Genetics Research Center. Material and methods In the majority of families (92%) at least two sibs were affected with MR and none had specific chromosomal syndromes such as Down syndrome. Standard cytogenetic techniques using high resolution GTG banding were carried out on all the patients. Results The overall chromosome abnormality rate contributing to mental retardation was 1.24% (4 cases), which comprised 46,XY,der(18)t(4;18)(q31.1;q23)mat; 45,XY,-21,-22,+der(22)t(21;22)(q21.1;q13.33)mat; 46,XY,rec(2)dup(2p)inv(2)(p25.1q37.3)pat, and 46,XY,der(11)t(10;11)(q25.2;q25)pat. Conclusions Although the most likely genetic cause of mental retardation in patients with consanguineous parents is autosomal recessive, the fact that 1.24% of our patients had chromosomal abnormalities emphasizes the importance of cytogenetic investigation as the first laboratory genetic tests for all MR patients. To our knowledge, this is the first report on the rate of chromosome abnormality among patients with idiopathic mental retardation from consanguineous marriages. PMID:22291774

  2. Analysis of CYP7B1 in non-consanguineous cases of hereditary spastic paraplegia.

    PubMed

    Schüle, Rebecca; Brandt, Elisabeth; Karle, Kathrin N; Tsaousidou, Maria; Klebe, Stephan; Klimpe, Sven; Auer-Grumbach, Michaela; Crosby, Andrew H; Hübner, Christian A; Schöls, Ludger; Deufel, Thomas; Beetz, Christian

    2009-04-01

    Hereditary spastic paraplegia (HSP) is a neurodegenerative condition defined clinically by lower limb spasticity and weakness. Homozygous mutations in CYP7B1 have been identified in several consanguineous families that represented HSP type 5 (SPG5), one of the many genetic forms of the disease. We used direct sequencing and multiplex ligation-dependent probe amplification to screen for CYP7B1 alterations in apparently sporadic HSP patients (n = 12) as well as index patients from non-consanguineous families with recessive (n = 8) and dominant (n = 8) transmission of HSP. One sporadic patient showing HSP as well as optic atrophy carried a homozygous nonsense mutation. Compound heterozygosity was observed in a recessive family with a clinically pure phenotype. A heterozygous missense change segregated in a small dominant family. We also found a significant association of a known coding polymorphism with cerebellar signs complicating a primary HSP phenotype. Our findings suggest CYP7B1 alterations to represent a rather frequent cause of HSP that should be considered in patients with various clinical presentations. PMID:18855023

  3. 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…

  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. PMID:17851452

  5. Mutations in the Alpha 1,2-Mannosidase Gene, MAN1B1, Cause Autosomal-Recessive Intellectual Disability

    PubMed Central

    Rafiq, Muhammad Arshad; Kuss, Andreas W.; Puettmann, Lucia; Noor, Abdul; Ramiah, Annapoorani; Ali, Ghazanfar; Hu, Hao; Kerio, Nadir Ali; Xiang, Yong; Garshasbi, Masoud; Khan, Muzammil Ahmad; Ishak, Gisele E.; Weksberg, Rosanna; Ullmann, Reinhard; Tzschach, Andreas; Kahrizi, Kimia; Mahmood, Khalid; Naeem, Farooq; Ayub, Muhammad; Moremen, Kelley W.; Vincent, John B.; Ropers, Hans Hilger; Ansar, Muhammad; Najmabadi, Hossein

    2011-01-01

    We have used genome-wide genotyping to identify an overlapping homozygosity-by-descent locus on chromosome 9q34.3 (MRT15) in four consanguineous families affected by nonsyndromic autosomal-recessive intellectual disability (NS-ARID) and one in which the patients show additional clinical features. Four of the families are from Pakistan, and one is from Iran. Using a combination of next-generation sequencing and Sanger sequencing, we have identified mutations in the gene MAN1B1, encoding a mannosyl oligosaccharide, alpha 1,2-mannosidase. In one Pakistani family, MR43, a homozygous nonsense mutation (RefSeq number NM_016219.3: c.1418G>A [p.Trp473∗]), segregated with intellectual disability and additional dysmorphic features. We also identified the missense mutation c. 1189G>A (p.Glu397Lys; RefSeq number NM_016219.3), which segregates with NS-ARID in three families who come from the same village and probably have shared inheritance. In the Iranian family, the missense mutation c.1000C>T (p.Arg334Cys; RefSeq number NM_016219.3) also segregates with NS-ARID. Both missense mutations are at amino acid residues that are conserved across the animal kingdom, and they either reduce kcat by ∼1300-fold or disrupt stable protein expression in mammalian cells. MAN1B1 is one of the few NS-ARID genes with an elevated mutation frequency in patients with NS-ARID from different populations. PMID:21763484

  6. Gastrocnemius recession.

    PubMed

    Anderson, John G; Bohay, Donald R; Eller, Erik B; Witt, Bryan L

    2014-12-01

    The Grand Rapids Arch Collapse classifications create a novel system for categorizing and correlating numerous common foot and ankle conditions related to a falling arch. The algorithm for treating these conditions is exceptionally replicable and has excellent outcomes. Gastrocnemius equinus diagnosis plays a crucial role in the pathology of arch collapse. A contracture of the gastrocnemius muscle is increasingly recognized as the cause of several foot and ankle conditions. The authors have expanded their indications for gastrocnemius recession to include arch pain without radiographic abnormality, calcaneus apophysitis, plantar fasciitis/fibromas, Achilles tendonosis, early-onset diabetic Charcot arthropathy, and neuropathic forefoot ulcers. PMID:25456721

  7. Consanguineous marriages in the province of Antalya, Turkey.

    PubMed

    Alper, O M; Erengin, H; Manguoğlu, A E; Bilgen, T; Cetin, Z; Dedeoğlu, N; Lüleci, G

    2004-01-01

    To assess the trends in the frequency and the medical effects of consanguinity in the south coast of Turkish population using local and national data in the last 11 years. This cross-sectional study was carried out in Manavgat province, which is a major tourism center on the Mediterranean coast of Turkey. The authors studied consanguineous marriages in rural and urban population in the Mediterranean coast, Manavgat province, Turkey, via a 1500 random survey sample of married couples. There has been a significant increase in the incidence of consanguineous marriages in rural areas (40.7%) since 1989 in the southern population of Turkey. The results showed that the most frequent type of marriage was between the first cousins. It is found that there is no statistically significant difference between the consanguineous and non-consanguineous marriages in the different age groups. The results were discussed on the basis of educational status, reasons for having consanguineous marriages and the general medical effects as well as with the relation of congenital malformations. The custom of consanguineous unions in the Mediterranean population of Turkey is still extremely high, and preventive measures should be done to decrease its frequency and associated complications. PMID:15183745

  8. 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

  9. Deletion mutation in BSCL2 gene underlies congenital generalized lipodystrophy in a Pakistani family

    PubMed Central

    2013-01-01

    Background Congenital generalized lipodystrophy (CGL) also known as Berardinelli-Seip Congenital Lipodystrophy (BSCL) is a genetically heterogeneous disorder characterized by loss of adipose tissues, Acanthosis nigricans, diabetes mellitus, muscular hypertrophy, hepatomegaly and hypertriglyceridemia. There are four subclinical phenotypes of CGL (CGL1-4) and mutations in four genes AGPAT2, BSCL2, CAV1 and PTRF have been assigned to each type. Methods The study included clinical and molecular investigations of CGL disease in a consanguineous Pakistani family. For mutation screening all the coding exons including splice junctions of AGPAT2, BSCL2, CAV1 and PTRF genes were PCR amplified and sequenced directly using an automated DNA sequencer ABI3730. Results Sequence analysis revealed a single base pair deletion mutation (c.636delC; p.Tyr213ThrfsX20) in exon 5 of BSCL2 gene causing a frame shift and premature termination codon. Conclusion Mutation identified here in BSCL2 gene causing congenital generalized lipodystrophy is the first report in Pakistani population. The patients exhibited characteristic features of generalized lipodystrophy, Acanthosis nigricans, diabetes mellitus and hypertrophic cardiomyopathy. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1913913076864247. PMID:23659685

  10. Whole exome sequencing unravels disease-causing genes in consanguineous families in Qatar.

    PubMed

    Fahiminiya, S; Almuriekhi, M; Nawaz, Z; Staffa, A; Lepage, P; Ali, R; Hashim, L; Schwartzentruber, J; Abu Khadija, K; Zaineddin, S; Gamal, H; Majewski, J; Ben-Omran, T

    2014-08-01

    Whole exome sequencing (WES) has greatly facilitated the identification of causal mutations for diverse human genetic disorders. We applied WES as a molecular diagnostic tool to identify disease-causing genes in consanguineous families in Qatar. Seventeen consanguineous families with diverse disorders were recruited. Initial mutation screening of known genes related to the clinical diagnoses did not reveal the causative mutations. Using WES approach, we identified the definitive disease-causing mutations in four families: (i) a novel nonsense homozygous (c.1034C>G) in PHKG2 causing glycogen storage disease type 9C (GSD9C) in a male with initial diagnosis of GSD3; (ii) a novel homozygous 1-bp deletion (c.915del) in NSUN2 in a male proband with Noonan-like syndrome; (iii) a homozygous SNV (c.1598C>G) in exon 11 of IDUA causing Hurler syndrome in a female proband with unknown clinical diagnosis; (iv) a de novo known splicing mutation (c.1645+1G>A) in PHEX in a female proband with initial diagnosis of autosomal recessive hypophosphatemic rickets. Applying WES as a diagnostic tool led to the unambiguous identification of disease-causing mutations in phenotypically complex disorders or correction of the initial clinical diagnosis in ˜25% of our cases. PMID:24102521

  11. 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

  12. 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

  13. The Perils of SNP Microarray Testing: Uncovering Unexpected Consanguinity

    PubMed Central

    Tarini, Beth A.; Konczal, Laura; Goldenberg, Aaron J.; Goldman, Edward B.; McCandless, Shawn E.

    2013-01-01

    Background While single nucleotide polymorphism (SNP) chromosomal microarrays identify areas of small genetic deletions/duplications, they can also reveal regions of homozygosity indicative of consanguinity. As more non-geneticists order SNP microarrays, they must prepare for the potential ethical, legal and social issues that result from revelation of unanticipated consanguinity. Patient An infant with multiple congenital anomalies underwent SNP microarray testing. Results The results of the SNP microarray revealed several large regions of homozygosity that indicated identity by descent most consistent with a second or third degree relative mating (e.g., uncle/ niece, half brother/sister, first cousins). Mother was not aware of the test's potential to reveal consanguinity. When informed of the test results, she reluctantly admitted to being raped by her half-brother around the time of conception. Conclusions During the pre-testing consent process, providers should inform parents that SNP microarray testing could reveal consanguinity. Providers must also understand the psychological implications, as well as the legal and moral obligations, that accompany SNP microarray results that indicate consanguinity. PMID:23827427

  14. Consanguinity and susceptibility to infectious diseases in humans

    PubMed Central

    Lyons, Emily J.; Frodsham, Angela J.; Zhang, Lyna; Hill, Adrian V.S.; Amos, William

    2009-01-01

    Studies of animal populations suggest that low genetic heterozygosity is an important risk factor for infection by a diverse range of pathogens, but relatively little research has looked to see whether similar patterns exist in humans. We have used microsatellite genome screen data for tuberculosis (TB), hepatitis and leprosy to test the hypothesis that inbreeding depression increases risk of infection. Our results indicate that inbred individuals are more common among our infected cases for TB and hepatitis, but only in populations where consanguineous marriages are common. No effect was found either for leprosy, which is thought to be oligogenic, or for hepatitis in Italy where consanguineous marriages are rare. Our results suggest that consanguinity is an important risk factor in susceptibility to infectious diseases in humans. PMID:19324620

  15. 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. PMID:22246887

  16. 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…

  17. 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…

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

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

    PubMed

    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

  4. 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

  5. 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.

  6. 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…

  7. Novel mutations in WWOX, RARS2, and C10orf2 genes in consanguineous Arab families with intellectual disability.

    PubMed

    Alkhateeb, Asem M; Aburahma, Samah K; Habbab, Wesal; Thompson, I Richard

    2016-08-01

    Intellectual disability is a heterogeneous disease with many genes and mutations influencing the phenotype. Consanguineous families constitute a rich resource for the identification of rare variants causing autosomal recessive disease, due to the effects of inbreeding. Here, we examine three consanguineous Arab families, recruited in a quest to identify novel genes/mutations. All the families had multiple offspring with non-specific intellectual disability. We identified homozygosity (autozygosity) intervals in those families through SNP genotyping and whole exome sequencing, with variants filtered using Ingenuity Variant Analysis (IVA) software. The families showed heterogeneity and novel mutations in three different genes known to be associated with intellectual disability. These mutations were not found in 514 ethnically matched control chromosomes. p.G410C in WWOX, p.H530Y in RARS2, and p.I69F in C10orf2 are novel changes that affect protein function and could give new insights into the development and function of the central nervous system. PMID:27121845

  8. [Gingival recessions and orthodontics].

    PubMed

    Renkema, A M; Padmos, J A D; de Quincey, G de

    2015-11-01

    Gingival recessions represent the most visible periodontal disease. The prevalence of gingival recessions is high. The root surface is literally exposed to negative influences such as erosion, abrasion, discoloration and decay. Moreover, gingival recessions can affect the quality of life by increased thermal sensitivity and reduced dento-gingival aesthetics. The aetiology of gingival recessions is complex and considered to be multifactorial. In order to prevent the development of gingival recessions during and after orthodontic treatment, several factors should be taken into account, among which maintenance of optimal oral hygiene and respect for the 'biological envelope' are decisive. Once gingival recessions have developed, orthodontic therapy can play a positive role in their treatment. PMID:26569002

  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. Consanguinity Associated With Increased Risk for Bipolar I Disorder in Egypt

    PubMed Central

    Mansour, Hader; Klei, Lambertus; Wood, Joel; Talkowski, Michael; Chowdari, Kodavali; Fathi, Warda; Eissa, Ahmed; Yassin, Amal; Salah, Hala; Tobar, Salwa; El-Boraie, Hala; Gaafar, Hanan; Elassy, Mai; Ibrahim, Nahed E.; El-Bahaei, Wafaa; Elsayed, Mohamed; Shahda, Mohamed; Sheshtawy, Eman El; El-Boraie, Osama; El-Chennawi, Farha; Devlin, Bernie; Nimgaonkar, Vishwajit L.

    2016-01-01

    We aimed to contrast rates of consanguinity among patients with bipolar I disorder (BP1) and controls in a population with customary consanguineous marriages (i.e., marriage between related individuals). Consanguinity increases risk for numerous monogenic and polygenic diseases. Whether the risk for BP1 increases with consanguinity has not been investigated systematically. Two independent studies were conducted in Egypt: (1) Case–control study 93 patients with BP1, 90 screened adult control individuals, and available parents. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms (“DNA-based” rate); and from family history data (“self report”); (2) Epidemiological survey: total of 1,584 individuals were screened, from whom self-reported consanguinity data were obtained for identified BP1 cases (n=35) and 150 randomly selected, unaffected control individuals. DNA-based consanguinity rates showed significant case–control control differences (P=0.0039). Self-reported consanguinity rates were also elevated among BP1 patients in both samples (Study #1 OR=2.66, 95% confidence intervals, CI: 1.34, 5.29; Study #2: OR=4.64, 95% CI: 2.01, 10.34). In conclusion, two independent, systematic studies indicate increased consanguinity among Egyptian BP1 patients in the Nile delta region. Self-reported estimates of consanguinity are bolstered by DNA-based estimates, and both show significant case–control differences for BP1. PMID:19152378

  11. HACE1 deficiency causes an autosomal recessive neurodevelopmental syndrome

    PubMed Central

    Hollstein, Ronja; Parry, David A; Nalbach, Lisa; Logan, Clare V; Strom, Tim M; Hartill, Verity L; Carr, Ian M; Korenke, Georg C; Uppal, Sandeep; Ahmed, Mushtaq; Wieland, Thomas; Markham, Alexander F; Bennett, Christopher P; Gillessen-Kaesbach, Gabriele; Sheridan, Eamonn G; Kaiser, Frank J; Bonthron, David T

    2015-01-01

    Background The genetic aetiology of neurodevelopmental defects is extremely diverse, and the lack of distinctive phenotypic features means that genetic criteria are often required for accurate diagnostic classification. We aimed to identify the causative genetic lesions in two families in which eight affected individuals displayed variable learning disability, spasticity and abnormal gait. Methods Autosomal recessive inheritance was suggested by consanguinity in one family and by sibling recurrences with normal parents in the second. Autozygosity mapping and exome sequencing, respectively, were used to identify the causative gene. Results In both families, biallelic loss-of-function mutations in HACE1 were identified. HACE1 is an E3 ubiquitin ligase that regulates the activity of cellular GTPases, including Rac1 and members of the Rab family. In the consanguineous family, a homozygous mutation p.R219* predicted a truncated protein entirely lacking its catalytic domain. In the other family, compound heterozygosity for nonsense mutation p.R748* and a 20-nt insertion interrupting the catalytic homologous to the E6-AP carboxyl terminus (HECT) domain was present; western blot analysis of patient cells revealed an absence of detectable HACE1 protein. Conclusion HACE1 mutations underlie a new autosomal recessive neurodevelopmental disorder. Previous studies have implicated HACE1 as a tumour suppressor gene; however, since cancer predisposition was not observed either in homozygous or heterozygous mutation carriers, this concept may require re-evaluation. PMID:26424145

  12. A clinical variant in SCN1A inherited from a mosaic father cosegregates with a novel variant to cause Dravet syndrome in a consanguineous family.

    PubMed

    Tuncer, Feyza N; Gormez, Zeliha; Calik, Mustafa; Altiokka Uzun, Gunes; Sagiroglu, Mahmut S; Yuceturk, Betul; Yuksel, Bayram; Baykan, Betul; Bebek, Nerses; Iscan, Akin; Ugur Iseri, Sibel A; Ozbek, Ugur

    2015-07-01

    A consanguineous family from Turkey having two children with intellectual disability exhibiting myoclonic, febrile and other generalized seizures was recruited to identify the genetic origin of these phenotypes. A combined approach of SNP genotyping and exome sequencing was employed both to screen genes associated with Dravet syndrome and to detect homozygous variants. Analysis of exome data was extended further to identify compound heterozygosity. Herein, we report identification of two paternally inherited genetic variants in SCN1A (rs121917918; p.R101Q and p.I1576T), one of which was previously implicated in Dravet syndrome. Interestingly, the previously reported clinical variant (rs121917918; p.R101Q) displayed mosaicism in the blood and saliva of the father. The study supported the genetic diagnosis of affected children as Dravet syndrome possibly due to the combined effect of one clinically associated (rs121917918; p.R101Q) and one novel (p.I1576T) variants in SCN1A gene. This finding is important given that heterozygous variants may be overlooked in standard exome scans of consanguineous families. Thus, we are presenting an interesting example, where the inheritance of the condition may be misinterpreted as recessive and identical by descent due to consanguinity and mosaicism in one of the parents. PMID:25986186

  13. 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…

  14. 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)…

  15. 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…

  16. 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…

  17. Recess Makes Kids Smarter

    ERIC Educational Resources Information Center

    Adams, Caralee

    2011-01-01

    Recess has been scaled back or cut altogether in a number of schools around the country. The trend can be traced back to the late eighties and was accelerated under No Child Left Behind. Districts under pressure to show academic progress began to squeeze as much instruction into the day as possible. Others eliminated recess because of concerns…

  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. Effect of consanguinity on Argentinean Angus beef DNA traceability.

    PubMed

    Baldo, A; Rogberg-Muñoz, A; Prando, A; Mello Cesar, A S; Lirón, J P; Sorarrain, N; Ramelli, P; Posik, D M; Pofcher, E; Ripoli, M V; Beretta, E; Peral-García, P; Vaca, R; Mariani, P; Giovambattista, G

    2010-08-01

    Since the 1990s several authors have envisaged the use of DNA to certify meat origin. Two major parameters must be assessed before a DNA based traceability protocol can be implemented in the food chain: (i) the information content of a DNA marker set in a specific livestock breed or group of breeds; (ii) the minimum number of DNA markers needed to obtain a statistically acceptable match probability. The objective of the present work was to establish the effect of different levels of inbreeding in the matching efficiency, and the minimum number of microsatellite markers needed, in a DNA based meat traceability program, starting from an 11-microsatellite marker panel. Samples were obtained from beef production farms in South America, where animals are typically bred under pasture-based extensive conditions. Three groups of animals with different consanguinity rates were sampled. Exclusion power (Q) was higher than 0.999998 and match probability lower than 3.01E-08, for the whole set of markers within each group. Both values were affected by consanguinity. To reach a two mismatch criteria exclusion power (Q(2)) of 99.99, six markers were needed in unrelated animals whereas seven markers were needed in related animals. To reach Q(2)=99.9999, 8 and 10 microsatellite markers, respectively, were needed. In general, one or two more microsatellite markers were needed to identify consanguineous animals. This study proved the DNA marker set used to be suitable for the identification of the meat from all slaughtered animals in Argentina, per week, month, and year. PMID:20416796

  20. Suicidal ideation in Pakistani college students.

    PubMed

    Khokher, Sehar; Khan, Murad M

    2005-01-01

    Suicidal behavior includes ideation, attempts and completed suicides. Information on suicidal behavior from Pakistan, a conservative South Asian Islamic country, is lacking. To address the issue, a pilot study was carried out to assess the prevalence of suicidal ideation in Pakistani college students. Suicidal ideation was assessed on the basis of responses to four questions contained in the depression subscale of the General Health Questionnaire-28. Of the total 217 completed questionnaires, the overall rate of suicidal ideation was 31.4%. While there was no significant difference between genders, more females (33%) than males (29.2%) responded positively. Respondents belonging to single parent families and those living at home, compared to those using hostel facilities, reported higher rates. The reported rate in our sample is higher than similar studies conducted elsewhere. There is the need for more information in this important area of suicidal behavior, including studying such feelings in school going children as well as in a larger community sample. The findings of such studies can contribute to our understanding of the suicidal process in the Pakistani population and to address it at various levels. PMID:16276755

  1. Consanguinity profile in the Gaza Strip of Palestine: large-scale community-based study.

    PubMed

    Sirdah, Mahmoud M

    2014-02-01

    Consanguineous marriages which have been practiced throughout history continue to be practiced within different ethnic, religious and social groups to varying degrees with highest prevalences in North Africa, Middle East and central and south Asia. In the Gaza Strip of Palestine, little is known about the consanguinity profile, so the present large-scale study aims to explore the consanguinity profile of two generations using data from the β-thalassemia premarital screening program. Sociodemographic data analysis included 156,635 (141,200 males and 15,435 females) persons and their parents, representing 141,200 couples who were referred to the Thalassemia and Hemophilia Center for premarital testing. In addition, the consanguinity characteristics of parents of 217 transfusion-dependent β-thalassemic non-sibling patients were analyzed. Results revealed a significant decrease in the overall prevalence of consanguineous (first- and second-cousin) marriages between the previous (fathers') generation (45.2%) and the current (groom/bride) generation (39.9%). Among the five governorates of the Gaza Strip, records of Gaza Governorate revealed the lowest occurrence (36.9% current generation and 42.1% previous generation) of consanguineous marriages, as compared to all others. Consanguineous marriages are significantly higher in semi-urban areas (41.6%) than in urban areas (39.1%) in the current generation (previous generation, 46.4% vs 44.7%, respectively). Compound consanguinity (two generation) and a single level of consanguinity were seen in 20.7% and 43.7%, respectively, of the cases. The average age of those with first-cousin marriages is significantly lower (22.4±4.4 years) than those with second-cousin marriages (24.3±6.1 years) and the non-consanguineous (26.5±8.2 years). The rate of consanguineous marriages among never married people (42.2%) is significantly much higher than the rate of people with multiple marriages (18.1%). About 74.7% of the non

  2. Mutations in the lipase-H gene causing autosomal recessive hypotrichosis and woolly hair.

    PubMed

    Mehmood, Sabba; Jan, Abid; Muhammad, Dost; Ahmad, Farooq; Mir, Hina; Younus, Muhammad; Ali, Ghazanfar; Ayub, Muhammad; Ansar, Muhammad; Ahmad, Wasim

    2015-08-01

    Hypotrichosis is characterised by sparse scalp hair, sparse to absent eyebrows and eyelashes, or absence of hair from other parts of the body. In few cases, the condition is associated with tightly curled woolly scalp hair. The present study searched for disease-causing sequence variants in the genes in four Pakistani lineal consanguineous families exhibiting features of hypotrichosis or woolly hair. A haplotype analysis established links in all four families to the LIPH gene located on chromosome 3q27.2. Subsequently, sequencing LIPH identified a novel non-sense mutation (c.328C>T; p.Arg110*) in one and a previously reported 2-bp deletion mutation (c.659_660delTA, p.Ile220ArgfsX29) in three other families. PMID:24628704

  3. 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

  4. The frequency of consanguinity in Konya, Turkey, and its medical effects.

    PubMed

    Demirel, S; Kaplanoğlu, N; Acar, A; Bodur, S; Paydak, F

    1997-01-01

    This study was conducted in the town of Konya, Turkey, on 1120 randomly selected women to find out the overall rate of consanguineous marriages among couples. The frequency of consanguineous marriages was found to be 23.2%. It was found that 14.6% of this figure was first cousin marriages and the rest was 8.6%. Consanguineous marriages were higher among women born in villages compared to those born in provinces and the town center. Based on the findings, it was not too difficult to say: the higher the level of education of women, the lower the rate of consanguineous marriages. The number of children with an abnormality was high in consanguineous marriages, while the frequency of spontaneous abortion, still-birth and infant death remained the same. PMID:9457498

  5. HLA-DRB1, -DQA1 and -DQB1 alleles and haplotypes in first-generation Pakistani immigrants in Norway.

    PubMed

    Rønningen, K S; Yap, S E; Brandal, K; Stormyr, A; Lie, B A; Rasmussen, T; Stray-Pedersen, B; Akselsen, H E

    2012-04-01

    Human leucocyte antigen (HLA) polymorphisms among immigrants from Pakistan have not been well investigated. Immigration to Norway started in the late 1960s for working purposes. From 1975, immigration was mainly for marriages and family reunion. When recruiting couples for a birth cohort study, we ended up with 65.5% of the 374 parents genotyped being closely related. This was also reflected in that 21% of newborns were homozygotes for their DRB1-DQA1-DQB1 genotype. For being able to study HLA class II genes frequencies among unrelated individuals, we had to exclude 195 of the parents from data analysis. High-resolution typing for the DRB1 locus, low/intermediate for the DQA1 locus and resolution genotyping for the DQB1 locus were performed in all the 179 parents and their newborns from the Punjab province of Pakistan. We identified 25 DRB1, nine DQA1 and 14 DRB1 alleles in the 179 unrelated parents included in our analysis. The most frequent alleles were DRB1*03:01:01 (15.9%) and DRB1*07:01:01 (15.9%), DQA1*01:03 (22.1%) and DQB1*02:01:01 (26.0%). Forty-one haplotypes were identified, including DRB1*13:02:01-DQA1*01:02-DQB1*06:03:01, not earlier reported. Supported by the few earlier reports on Pakistani groups living in Pakistan, it appears that alleles found among those living in Norway are of Indo-European or mixed ethnic origin. This study provides the first comprehensive report of HLA class II alleles and haplotypes in Norwegian Pakistani immigrants. When the unrelated parents were compared with all parents genotyped, there were, however, no significant differences in allele frequencies, confirming that consanguineous marriages are usual in Pakistan. PMID:22171671

  6. 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

  7. 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.

  8. 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.

  9. Pentalogy of Cantrell: report of a case with consanguineous parents.

    PubMed

    Pachajoa, Harry; Barragán, Arelis; Potes, Angela; Torres, Javier; Isaza, Carolina

    2010-01-01

    Pentalogy of Cantrell is a syndrome evidencing five anomalies: a midline, upper abdominal wall abnormality; lower sternal defect; anterior diaphragmatic defect; diaphragmatic pericardial defect, and congenital abnormalities of the heart. Its prevalence is one in every 65,000 live births and a survival rate that is low if the fall the five defects are present or the gravity of the cardiac anomalies. It may be diagnosed during the first trimester obstetric ultrasound. For postnatal care, emission-computed tomography and magnetic resonance imaging is recommended for a clear definition of the extent of the defect and to design a course of corrective surgery. Herein, a case of pentology of Cantrell is reported for a child offspring of consanguineous parents. PMID:21713350

  10. A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family.

    PubMed Central

    Bujakowska, Kinga; Mohand-Saïd, Saddek; Tronche, Sophie; Lancelot, Marie-Elise; Antonio, Aline; Germain, Aurore; Lonjou, Christine; Carpentier, Wassila; Sahel, José-Alain; Bhattacharya, Shomi; Zeitz, Christina

    2011-01-01

    Purpose To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition. Methods A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog–drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71). Subsequently, genome-wide homozygosity mapping was performed in DNA samples from available family members using a 700K single nucleotide polymorphism (SNP) microarray. Candidate genes present in the significantly large homozygous regions were screened for mutations using Sanger sequencing. Results The largest homozygous region (~11 Mb) in the affected family members was mapped to chromosome 9, which harbors deafness, autosomal recessive 31 (DFNB31; a gene previously associated with Usher syndrome). Mutation analysis of DFNB31 in the index patient identified a novel one-base-pair deletion (c.737delC), which is predicted to lead to a truncated protein (p.Pro246HisfsX13) and co-segregated with the disease in the family. Ophthalmic examination of the index patient and the affected siblings showed severe rod-cone dystrophy. Pure tone audiometry revealed a moderate hearing loss in the index patient, whereas the affected siblings were reported with more profound and early onset hearing impairment. Conclusions We report a novel truncating mutation in DFNB31 associated with severe rod-cone dystrophy and varying degrees of hearing impairment in a consanguineous family of Portuguese origin. This is the second report of DFNB31 implication in Usher type 2. PMID:21738389

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

    PubMed Central

    Teebi, A S

    1994-01-01

    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. PMID:8014972

  12. Association among Education Level, Occupation Status, and Consanguinity in Tunisia and Croatia

    PubMed Central

    Kerkeni, Emna; Monastiri, Kamel; Saket, Besma; Rudan, Diana; Zgaga, Lina; Ben Cheikh, Hassen

    2006-01-01

    Aim To investigate the association between education level, occupation status (a proxy for socio-economic status), and consanguinity in 2 large data sets from Tunisia and Croatia countries with different attitudes toward consanguinity. Methods The sample of 1016 students, attending 5 university institutions in Monastir, Tunisia, were interviewed about the educational level and occupation status of their parents and the degree of parental relatedness. In Croatia, a sample of 1001 examinees from 9 isolated island populations was interviewed about their own educational level, occupation status, and consanguinity. Results Prevalence of consanguinity (offspring of second cousins or closer) among 1016 Tunisian students was 20.1%, and 9.3% among 1001 Croatian isolates. In Tunisia, the association between consanguinity and both parental degree of education and parental occupation status was highly significant in women (P<0.001), but not significant in men. In Croatia, no statistically significant associations were noted, although there was a consistent trend of increased prevalence of consanguinity with lower education level or occupation status in both genders, but more pronounced in women. Conclusion Association between education level, socio-economic status, and consanguinity needs to be taken into account in inbreeding studies in human populations. The relationship may be specific for each studied population and highly dependent on the cultural context. It is generally more pronounced among women in most settings. PMID:16912991

  13. 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. PMID:8359962

  14. 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. PMID:3686072

  15. Clinical and pathological features of an autosomal recessive neuropathy.

    PubMed

    Bouldin, T W; Riley, E; Hall, C D; Swift, M

    1980-06-01

    Two siblings are described, ages 49 and 45 years, having a distinct hereditary motor and sensory neuropathy (HMSN) with severe peroneal nerve involvement. The neuropathic symptoms began in childhood. Both patients have sensorineural deafness. The proband was found to have a cardiac conduction abnormality in the absence of known ischemic heart disease. Electrodiagnostic studies were consistent with a demyelinating peripheral neuropathy. The presence of parental consanguinity and absence of affected individuals in succeeding or preceding generations suggested that the sensorimotor neuropathy in this family is inherited in an autosomal recessive manner. The sural nerve of the proband had significant loss of myelinated fibers and demyelination but few regenerating myelinated fibers and no onion-bulbs. The pathological findings, while nonspecific, are not characteristic of the hypertrophic, neuronal or intermediate types of HMSN. PMID:6247456

  16. Diencephalic-mesencephalic junction dysplasia: a novel recessive brain malformation.

    PubMed

    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

    2012-08-01

    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 axial sections. Additional imaging features included variable degrees of supratentorial ventricular dilatation and hypoplasia to complete agenesis of the corpus callosum. Diffusion tensor imaging showed diffuse hypomyelination and lack of an identifiable corticospinal tract. All patients displayed severe cognitive impairment, post-natal progressive microcephaly, axial hypotonia, spastic quadriparesis and seizures. Autistic features were noted in older cases. Talipes equinovarus, non-obstructive cardiomyopathy and persistent hyperplastic primary vitreous were additional findings in two families. One of the patients required shunting for hydrocephalus; however, this yielded no change in ventricular size suggestive of dysplasia rather than obstruction. We propose the term 'diencephalic-mesencephalic junction dysplasia' to characterize this autosomal recessive malformation. PMID:22822038

  17. 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

  18. Exploring Identity in Muslim Moroccan and Pakistani Immigrant Women.

    PubMed

    Giuliani, Cristina; Tagliabue, Semira

    2015-02-01

    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. 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…

  20. Educational Finance in Recession.

    ERIC Educational Resources Information Center

    Lewin, Keith

    1986-01-01

    Discusses two interacting sources limiting educational expenditures in developing nations in light of the impact of the global economic recession: (1) factors affecting overall levels of public expenditures and (2) factors affecting educational priority in the national budget. Offers requirements for an effective response to these challenges. (TRS)

  1. 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)

  2. A 5-year survey of biopsy proven kidney diseases in Lebanon: significant variation in prevalence of primary glomerular diseases by age, population structure and consanguinity

    PubMed Central

    Karnib, Hussein H.; Gharavi, Ali G.; Aftimos, Georges; Mahfoud, Ziyad; Saad, Reem; Gemayel, Elias; Masri, Badiaa; Assaad, Shafika; Badr, Kamal F.; Ziyadeh, Fuad N.

    2010-01-01

    Background. Differences in epidemiology of kidney disease across the Middle East may arise from variations in indication for biopsy, environmental exposure and socio-economic status. The Lebanese population is composed of different ethnicities, with distinct ancestry and religion, enabling comparison of their effect on the prevalence of kidney disease within a confined geographic setting and uniform practices. Here we report 5 years’ detailed epidemiology of renal diseases, based on histological diagnosis, in a sample from three large pathology centres in Lebanon. Methods. Records of renal biopsies analysed at the American University of Beirut Medical Center, Hotel Dieu de France Hospital and the Institut National de Pathologie from January 2003 till December 2007 were retrospectively examined. We recorded the following data for each patient: age, gender, indication for renal biopsy and histopathological diagnosis. Religious affiliation and parents’ consanguinity were recorded when feasible. Results. The mean age at renal biopsy was 36.76 ± 20 years (range 1–84). The most common diagnosis was mesangioproliferative glomerulonephritis (GN; 20%), followed by focal segmental glomerulosclerosis (13.2%). While there were no differences in age, gender or indications for biopsy among different religious affiliations, mesangioproliferative GN was significantly more frequent among Muslims (P = 0.039) and offspring of consanguineous unions (P = 0.036). On the other hand, focal segmental glomerulosclerosis was most prevalent in Christians (P < 0.001). Conclusions. Variation in the distribution of diagnoses between Muslim and Christian groups likely reflects differences in population structure and ancestry. In particular, the increased prevalence of mesangioproliferative GN among offspring of consanguineous unions in Muslims suggests a recessive genetic component to this disease which may be identified via homozygosity mapping. These findings have important

  3. Nutritional composition of Pakistani wheat varieties.

    PubMed

    Ikhtiar, Khan; Alam, Zeb

    2007-08-01

    Pakistani wheat varieties are grown over a wide agro-climatic range and as such are anticipated to exhibit yield and quality differences. It is therefore necessary to investigate the nutritional status of wheat varieties in terms of biochemical and physiochemical characteristics available for food and nutritional purposes in Pakistan. The result shows that wheat grains of different varieties contain a net protein level of 9.15%-10.27%, 2.15%-2.55% total fats, 1.72%-1.85% dietary fibers, 77.65x10(-6)-84.25x10(-6) of potassium and 7.70x10(-6)-35.90x10(-6) of sodium ions concentration, 0.24x10(-6)-0.84x10(-6) of phosphorus, 1.44%-2.10% ash, 31.108-43.602 g of thousand grain mass (TGM) and 8.38%-9.67% moisture contents. This study is significant in providing an opportunity to explore the available wheat varieties and to further improve their nutritional excellence and also essential for setting nutritional regulations for domestic and export purposes. PMID:17657856

  4. 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

  5. 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

  6. 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. PMID:26995144

  7. Consanguinity and recurrence risk of stillbirth and infant death.

    PubMed Central

    Stoltenberg, C; Magnus, P; Skrondal, A; Lie, R T

    1999-01-01

    OBJECTIVES: The aim of this study was to estimate the recurrence risk for stillbirth and infant death and compare results for offspring of first-cousin parents with results for offspring of unrelated parents. METHODS: The study population consisted of all single births with a previous sibling born in Norway between 1967 and 1994. Altogether, 629,888 births were to unrelated parents, and 3466 births were to parents who were first cousins. The risk of stillbirth and infant death was estimated for subsequent siblings contingent on parental consanguinity and survival of the previous sibling. RESULTS: For unrelated parents, the risk of early death (stillbirth plus infant death) for the subsequent sibling was 17 of 1000 if the previous child survived and 67 of 1000 if the previous child died before 1 year of age. For parents who were first cousins, the risk of early death for the subsequent sibling was 29 of 1000 if the previous child survived and 116 of 1000 if the previous child died. CONCLUSIONS: The risk of recurrence of stillbirth and infant death is higher for offspring of first-cousin parents compared with offspring of unrelated parents. PMID:10191794

  8. Vici syndrome in siblings born to consanguineous parents.

    PubMed

    Tasdemir, Sener; Sahin, Ibrahim; Cayır, Atilla; Yuce, Ihsan; Ceylaner, Serdar; Tatar, Abdulgani

    2016-01-01

    Vici syndrome (OMIM 242840) is a rare syndrome and since its initial description by Vici et al. [1988], only 29 cases have been reported. We describe two brothers from healthy consanguineous Turkish parents with psychomotor delay, congenital bilateral cataracts, high palate, long philtrum, micrognathia, fair hair, and skin. They both had general hypotonia and elevated muscle enzymes. Magnetic resonance imaging (MRI) of the brain confirmed agenesis of corpus callosum in both patients. Secundum type atrial septal defect (in Patient 1) and mild mitral, tricuspid, and pulmonary insufficiency (in Patient 2) were detected by echocardiographic examination. Immunological studies were normal, as were chromosome karyotype analyses (46, XY). Both children had bilateral cutaneous syndactyly between second and third toes and also bilateral sensorineural hearing loss. Patient 1 had poor feeding and regurgitation necessitating a feeding tube; mild laryngomalacia was subsequently detected by bronchoscopy. Mutation analysis in patient 2 showed a homozygous p.R2483* (c.7447C > T) mutation in EPG5 gene. We report a summary of the clinical findings in our patients and 29 cases from the literature. PMID:26395118

  9. A Brazilian family with Brown-Vialetto-van Laere syndrome with autosomal recessive inheritance.

    PubMed

    Malheiros, José Augusto; Camargos, Sarah Teixeira; Oliveira, José Teotonio de; Cardoso, Francisco E C

    2007-03-01

    We report the first Brazilian family with Brown-Vialetto-van Laere syndrome. The presence of consanguineous marriages and illness affecting three sisters and one niece support an autosomal recessive transmission. The age at onset of the illness ranged from 12 to 20 years old. The time interval between hearing loss and involvement of other cranial nerves varied from 3 to 12 years. MRI demonstrated bulbar atrophy and also high intensity signal at T2 weighted and fluid attenuated inversion recovery (FLAIR) sequences. PMID:17420823

  10. 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

  11. Van Maldergem syndrome: further characterisation and evidence for neuronal migration abnormalities and autosomal recessive inheritance

    PubMed Central

    Mansour, Sahar; Swinkels, Marielle; Terhal, Paulien A; Wilson, Louise C; Rich, Philip; Van Maldergem, Lionel; Zwijnenburg, Petra JG; Hall, Christine M; Robertson, Stephen P; Newbury-Ecob, Ruth

    2012-01-01

    We present six patients from five unrelated families with a condition originally described by Van Maldergem et al and provide follow-up studies of the original patient. The phenotype comprises a distinctive facial appearance that includes blepharophimosis, maxillary hypoplasia, telecanthus, microtia and atresia of the external auditory meatus, intellectual disability, digital contractures and skeletal anomalies together with subependymal and subcortical neuronal heterotopia. Affected patients typically have neonatal hypotonia, chronic feeding difficulties and respiratory problems. In our cohort, we have observed one instance of sibling recurrence and parental consanguinity in three of the families, indicating that autosomal recessive inheritance is likely. PMID:22473091

  12. Autosomal recessive hereditary motor and sensory neuropathy with mental retardation, optic atrophy and pyramidal signs.

    PubMed Central

    MacDermot, K D; Walker, R W

    1987-01-01

    A syndrome is described, consisting of severe neurogenic distal wasting, generalised muscle weakness, absent ankle reflexes, pyramidal signs, mental retardation, optic atrophy and retinal colloid bodies. A sural nerve biopsy from one case showed loss of nerve fibres suggesting the diagnosis of hereditary motor and sensory neuropathy. Progression of the disorder was very slow, all patients still being able to walk more than 20 years after the onset. The persons affected with this syndrome were two brothers and their female cousin from a large Gujerati pedigree where consanguinity was high. Autosomal recessive inheritance is therefore suggested. Images PMID:3479531

  13. Comparison of Consanguinity between Parents of Hearing Impaired and Public School Children with Estimation of Risk.

    PubMed

    Sattar, M A; Sultana, M T

    2015-10-01

    Deafness is the hidden disability and the most common human sensory defects which lead to poor educational and employment prospects of childhood. Is there any association of consanguinity and hearing loss or are there any difference of association of consanguinity and hearing loss in specialized and public school children and how much risk is associated?--were the research questions of this study. Total 428 participants have been selected randomly. Hearing impaired were 186 participants and 242 participants were normal hearing school boy. This was a case control, analytical, hypotheses testing study. In normal public school children group, consanguinity was present in 2.5% parents. The rest were married with non relatives. In parents of hearing impaired children group, consanguinity was very high (17.2%). Pearson chi-square test and Odds ratio analysis was done. The value was less than 0.05 and ratio was 8.173. The 'p' value of Pearson chi-square test was less than 0.05. So, the test was highly significant at 95% confidence interval. Odds ratio showed that the risk of profound sensorineural hearing loss in the baby of parents of consanguineous marriages 8.173 times higher than that of non consanguineous marriages. PMID:26620013

  14. 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. PMID:25558065

  15. 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

  16. 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…

  17. Workplace Learning in Pakistani Schools: A Myth or Reality?

    ERIC Educational Resources Information Center

    Nawab, Ali

    2011-01-01

    Purpose: Literature on workplace learning emphasizes that learning should be continually generated and negotiated in the workplace. How does this concept unfold in the developing context? This paper aims at understanding teachers' workplace learning and the conditions which influence such learning in a private school of Pakistani context.…

  18. 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

  19. Autosomal recessive cerebellar ataxias

    PubMed Central

    Palau, Francesc; Espinós, Carmen

    2006-01-01

    Autosomal recessive cerebellar ataxias (ARCA) are a heterogeneous group of rare neurological disorders involving both central and peripheral nervous system, and in some case other systems and organs, and characterized by degeneration or abnormal development of cerebellum and spinal cord, autosomal recessive inheritance and, in most cases, early onset occurring before the age of 20 years. This group encompasses a large number of rare diseases, the most frequent in Caucasian population being Friedreich ataxia (estimated prevalence 2–4/100,000), ataxia-telangiectasia (1–2.5/100,000) and early onset cerebellar ataxia with retained tendon reflexes (1/100,000). Other forms ARCA are much less common. Based on clinicogenetic criteria, five main types ARCA can be distinguished: congenital ataxias (developmental disorder), ataxias associated with metabolic disorders, ataxias with a DNA repair defect, degenerative ataxias, and ataxia associated with other features. These diseases are due to mutations in specific genes, some of which have been identified, such as frataxin in Friedreich ataxia, α-tocopherol transfer protein in ataxia with vitamin E deficiency (AVED), aprataxin in ataxia with oculomotor apraxia (AOA1), and senataxin in ataxia with oculomotor apraxia (AOA2). Clinical diagnosis is confirmed by ancillary tests such as neuroimaging (magnetic resonance imaging, scanning), electrophysiological examination, and mutation analysis when the causative gene is identified. Correct clinical and genetic diagnosis is important for appropriate genetic counseling and prognosis and, in some instances, pharmacological treatment. Due to autosomal recessive inheritance, previous familial history of affected individuals is unlikely. For most ARCA there is no specific drug treatment except for coenzyme Q10 deficiency and abetalipoproteinemia. PMID:17112370

  20. 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

  1. Deep sequencing reveals 50 novel genes for recessive cognitive disorders.

    PubMed

    Najmabadi, Hossein; Hu, Hao; Garshasbi, Masoud; Zemojtel, Tomasz; Abedini, Seyedeh Sedigheh; Chen, Wei; Hosseini, Masoumeh; Behjati, Farkhondeh; Haas, Stefan; Jamali, Payman; Zecha, Agnes; Mohseni, Marzieh; Püttmann, Lucia; Vahid, Leyla Nouri; Jensen, Corinna; Moheb, Lia Abbasi; Bienek, Melanie; Larti, Farzaneh; Mueller, Ines; Weissmann, Robert; Darvish, Hossein; Wrogemann, Klaus; Hadavi, Valeh; Lipkowitz, Bettina; Esmaeeli-Nieh, Sahar; Wieczorek, Dagmar; Kariminejad, Roxana; Firouzabadi, Saghar Ghasemi; Cohen, Monika; Fattahi, Zohreh; Rost, Imma; Mojahedi, Faezeh; Hertzberg, Christoph; Dehghan, Atefeh; Rajab, Anna; Banavandi, Mohammad Javad Soltani; Hoffer, Julia; Falah, Masoumeh; Musante, Luciana; Kalscheuer, Vera; Ullmann, Reinhard; Kuss, Andreas Walter; Tzschach, Andreas; Kahrizi, Kimia; Ropers, H Hilger

    2011-10-01

    Common diseases are often complex because they are genetically heterogeneous, with many different genetic defects giving rise to clinically indistinguishable phenotypes. This has been amply documented for early-onset cognitive impairment, or intellectual disability, one of the most complex disorders known and a very important health care problem worldwide. More than 90 different gene defects have been identified for X-chromosome-linked intellectual disability alone, but research into the more frequent autosomal forms of intellectual disability is still in its infancy. To expedite the molecular elucidation of autosomal-recessive intellectual disability, we have now performed homozygosity mapping, exon enrichment and next-generation sequencing in 136 consanguineous families with autosomal-recessive intellectual disability from Iran and elsewhere. This study, the largest published so far, has revealed additional mutations in 23 genes previously implicated in intellectual disability or related neurological disorders, as well as single, probably disease-causing variants in 50 novel candidate genes. Proteins encoded by several of these genes interact directly with products of known intellectual disability genes, and many are involved in fundamental cellular processes such as transcription and translation, cell-cycle control, energy metabolism and fatty-acid synthesis, which seem to be pivotal for normal brain development and function. PMID:21937992

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

    PubMed Central

    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

  3. 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

  4. 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

  5. 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. PMID:26892044

  6. 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

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

    PubMed Central

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

    1997-01-01

    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. PMID:9429142

  8. 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

  9. 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.

  10. 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

  11. 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…

  12. 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. PMID:17941037

  13. 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

  14. Comparative study of combustion product emissions of Pakistani coal briquettes and traditional Pakistani domestic fuels

    SciTech Connect

    Wachter, E.A.; Gammage, R.B.; Haas, J.W. III; Wilson, D.L.; DePriest, J.C.; Wade, J.; Ahmad, N.; Sibtain, F.; Zahid Raza, M.

    1992-10-01

    A comparative emissions study was conducted on combustion products of various solid domestic cooking fuels; the objective was to compare relative levels of organic and inorganic toxic emissions from traditional Pakistani fuels (wood, wood charcoal, and dried animal dung) with manufactured low-rank coal briquettes (Lakhra and Sor- Range coals) under conditions simulating domestic cooking. A small combustion shed 12 m{sup 3} internal volume, air exchange rate 14 h{sup {minus}1} was used to simulate south Asian cooking rooms. 200-g charges of the various fuels were ignited in an Angethi stove located inside the shed, then combusted to completion; effluents from this combustion were monitored as a function of time. Measurements were made of respirable particulates, volatile and semi-volatile organics, CO, SO{sub 2}, and NO{sub x}. Overall it appears that emissions from coal briquettes containing combustion amendments (slaked lime, clay, and potassium nitrate oxidizer) are no greater than emissions from traditional fuels, and in some cases are significantly lower; generally, emissions are highest for all fuels in the early stages of combustion.

  15. Comparative study of combustion product emissions of Pakistani coal briquettes and traditional Pakistani domestic fuels

    SciTech Connect

    Wachter, E.A.; Gammage, R.B.; Haas, J.W. III; Wilson, D.L. ); DePriest, J.C.; Wade, J. ); Ahmad, N.; Sibtain, F.; Zahid Raza, M. )

    1992-10-01

    A comparative emissions study was conducted on combustion products of various solid domestic cooking fuels; the objective was to compare relative levels of organic and inorganic toxic emissions from traditional Pakistani fuels (wood, wood charcoal, and dried animal dung) with manufactured low-rank coal briquettes (Lakhra and Sor- Range coals) under conditions simulating domestic cooking. A small combustion shed 12 m[sup 3] internal volume, air exchange rate 14 h[sup [minus]1] was used to simulate south Asian cooking rooms. 200-g charges of the various fuels were ignited in an Angethi stove located inside the shed, then combusted to completion; effluents from this combustion were monitored as a function of time. Measurements were made of respirable particulates, volatile and semi-volatile organics, CO, SO[sub 2], and NO[sub x]. Overall it appears that emissions from coal briquettes containing combustion amendments (slaked lime, clay, and potassium nitrate oxidizer) are no greater than emissions from traditional fuels, and in some cases are significantly lower; generally, emissions are highest for all fuels in the early stages of combustion.

  16. Gingival Recession: Review and Strategies in Treatment of Recession

    PubMed Central

    Pradeep, Koppolu; Rajababu, Palaparthy; Satyanarayana, Durvasula; Sagar, Vidya

    2012-01-01

    One of the most common esthetic concerns associated with the periodontal tissues is gingival recession. Gingival recession is the exposure of root surfaces due to apical migration of the gingival tissue margins; gingival margin migrates apical to the cementoenamel junction. Although it rarely results in tooth loss, marginal tissue recession is associated with thermal and tactile sensitivity, esthetic complaints, and a tendency toward root caries. This paper reviews etiology, consequences, and the available surgical procedures for the coverage of exposed root surfaces, including three case reports. PMID:23082256

  17. 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

  18. 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

  19. [Etiology of gingival recessions].

    PubMed

    Kleber, B M; Schenk, H J

    1989-11-01

    About every third patient of our department suffers from gingival recessions (g. r.): 1980, 1985, 1986, 1987 altogether 1039 patients from 4022. People at the age of 20-25 years are mainly affected: 44.4% of these patients in the age-group of 20-25 years suffer from g. r., 28.3% of patients suffering from l.P.a. are 20-25 years old. Patients diseased with g. r. (N = 60) show functional disturbances (79% at the 1st bicuspid, 72% at the 2nd bicuspid) during their occlusion movements to a great extent. Patients afflected by g.r. (N = 20) show in comparison to healthy people a smaller diameter of the canin's apical basis both in upper and lower jaw, a smaller circumference of the alveolar crest as well as an upper canin-crown which is turned out from the teeth arcus in a more labial direction. Prevention of g. r. involves individual oral health education to protect the vestibular gingiva from chronic brushing-trauma, an early follow-up, and a functional adjustment. PMID:2638999

  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. 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

  3. 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…

  4. 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…

  5. 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…

  6. Routes Into Education and Employment for Young Pakistani and Bangladeshi Women in the UK. Working Paper.

    ERIC Educational Resources Information Center

    Dale, Angela; Shaheen, Nusrat; Kalra, Virinder; Fieldhouse, E.

    Routes into education and employment for young Pakistani and Bangladeshi women in Oldham, England, were examined. The data sources were as follows: group discussions with Pakistani and Bangladeshi young people at different stages in the educational system and at an early stage of labor market participation; interviews with public and voluntary…

  7. Homozygosity Mapping in Leber Congenital Amaurosis and Autosomal Recessive Retinitis Pigmentosa in South Indian Families

    PubMed Central

    Srilekha, Sundaramurthy; Arokiasamy, Tharigopala; Srikrupa, Natarajan N.; Umashankar, Vetrivel; Meenakshi, Swaminathan; Sen, Parveen; Kapur, Suman; Soumittra, Nagasamy

    2015-01-01

    Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP) are retinal degenerative diseases which cause severe retinal dystrophy affecting the photoreceptors. LCA is predominantly inherited as an autosomal recessive trait and contributes to 5% of all retinal dystrophies; whereas RP is inherited by all the Mendelian pattern of inheritance and both are leading causes of visual impairment in children and young adults. Homozygosity mapping is an efficient strategy for mapping both known and novel disease loci in recessive conditions, especially in a consanguineous mating, exploiting the fact that the regions adjacent to the disease locus will also be homozygous by descent in such inbred children. Here we have studied eleven consanguineous LCA and one autosomal recessive RP (arRP) south Indian families to know the prevalence of mutations in known genes and also to know the involvement of novel loci, if any. Complete ophthalmic examination was done for all the affected individuals including electroretinogram, fundus photograph, fundus autofluorescence, and optical coherence tomography. Homozygosity mapping using Affymetrix 250K HMA GeneChip on eleven LCA families followed by screening of candidate gene(s) in the homozygous block identified mutations in ten families; AIPL1 – 3 families, RPE65- 2 families, GUCY2D, CRB1, RDH12, IQCB1 and SPATA7 in one family each, respectively. Six of the ten (60%) mutations identified are novel. Homozygosity mapping using Affymetrix 10K HMA GeneChip on the arRP family identified a novel nonsense mutation in MERTK. The mutations segregated within the family and was absent in 200 control chromosomes screened. In one of the eleven LCA families, the causative gene/mutation was not identified but many homozygous blocks were noted indicating that a possible novel locus/gene might be involved. The genotype and phenotype features, especially the fundus changes for AIPL1, RPE65, CRB1, RDH12 genes were as reported earlier. PMID:26147992

  8. 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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24619944

  10. 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

  11. Missense Mutations in CRYAB Are Liable for Recessive Congenital Cataracts

    PubMed Central

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

    2015-01-01

    Purpose This study was initiated to identify causal mutations responsible for autosomal recessive congenital cataracts in consanguineous familial cases. Methods Affected individuals underwent a detailed ophthalmological and clinical examination, and slit-lamp photographs were ascertained for affected individuals who have not yet been operated for the removal of the cataractous lens. Blood samples were obtained, and genomic DNA was extracted from white blood cells. A genome-wide scan was completed with short tandem repeat (STR) markers, and the logarithm of odds (LOD) scores were calculated. Protein coding exons of CRYAB were sequenced, bi-directionally. Evolutionary conservation was investigated by aligning CRYAB orthologues, and the expression of Cryab in embryonic and postnatal mice lens was investigated with TaqMan probe. Results The clinical and ophthalmological examinations suggested that all affected individuals had nuclear cataracts. Genome-wide linkage analysis suggested a potential region on chromosome 11q23 harboring CRYAB. DNA sequencing identified a missense variation: c.34C>T (p.R12C) in CRYAB that segregated with the disease phenotype in the family. Subsequent interrogation of our entire cohort of familial cases identified a second familial case localized to chromosome 11q23 harboring a c.31C>T (p.R11C) mutation. In silico analyses suggested that the mutations identified in familial cases, p.R11C and p.R12C will not be tolerated by the three-dimensional structure of CRYAB. Real-time PCR analysis identified the expression of Cryab in mouse lens as early as embryonic day 15 (E15) that increased significantly until postnatal day 6 (P6) with steady level of expression thereafter. Conclusion Here, we report two novel missense mutations, p.R11C and p.R12C, in CRYAB associated with autosomal recessive congenital nuclear cataracts. PMID:26402864

  12. Counting Pakistanis in the Middle East: problems and policy implications.

    PubMed

    Stahl, C W; Farooq-i-azam

    1990-01-01

    "Using Pakistan as a case study, this article focuses on the difficulties of measuring both the outflow of workers over time and the stock abroad at any particular time. The various estimates of the number of Pakistanis in the Middle East are evaluated and an alternative estimate is provided based on hitherto unused data from two major surveys of returning workers. The alternative estimate differs substantially from the others, the difference being attributed principally to clandestine worker immigration. The concluding section discusses the policy implications of inaccurate information about the numbers of workers abroad and the likely effects of the current Persian Gulf crisis on Pakistan's economy." PMID:12283581

  13. Diencephalic–mesencephalic junction dysplasia: a novel recessive brain malformation

    PubMed Central

    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 axial sections. Additional imaging features included variable degrees of supratentorial ventricular dilatation and hypoplasia to complete agenesis of the corpus callosum. Diffusion tensor imaging showed diffuse hypomyelination and lack of an identifiable corticospinal tract. All patients displayed severe cognitive impairment, post-natal progressive microcephaly, axial hypotonia, spastic quadriparesis and seizures. Autistic features were noted in older cases. Talipes equinovarus, non-obstructive cardiomyopathy and persistent hyperplastic primary vitreous were additional findings in two families. One of the patients required shunting for hydrocephalus; however, this yielded no change in ventricular size suggestive of dysplasia rather than obstruction. We propose the term ‘diencephalic–mesencephalic junction dysplasia’ to characterize this autosomal recessive malformation. PMID:22822038

  14. Mutations in HPCA Cause Autosomal-Recessive Primary Isolated Dystonia

    PubMed Central

    Charlesworth, Gavin; Angelova, Plamena R.; Bartolomé-Robledo, Fernando; Ryten, Mina; Trabzuni, Daniah; Stamelou, Maria; Abramov, Andrey Y.; Bhatia, Kailash P.; Wood, Nicholas W.

    2015-01-01

    Reports of primary isolated dystonia inherited in an autosomal-recessive (AR) manner, often lumped together as “DYT2 dystonia,” have appeared in the scientific literature for several decades, but no genetic cause has been identified to date. Using a combination of homozygosity mapping and whole-exome sequencing in a consanguineous kindred affected by AR isolated dystonia, we identified homozygous mutations in HPCA, a gene encoding a neuronal calcium sensor protein found almost exclusively in the brain and at particularly high levels in the striatum, as the cause of disease in this family. Subsequently, compound-heterozygous mutations in HPCA were also identified in a second independent kindred affected by AR isolated dystonia. Functional studies suggest that hippocalcin might play a role in regulating voltage-dependent calcium channels. The identification of mutations in HPCA as a cause of AR primary isolated dystonia paves the way for further studies to assess whether “DYT2 dystonia” is a genetically homogeneous condition or not. PMID:25799108

  15. 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

  16. Institutional protocol to manage consanguinity detected by genetic testing in pregnancy in a minor.

    PubMed

    Chen, Laura P; Beck, Anita E; Tsuchiya, Karen D; Chow, Penny M; Mirzaa, Ghayda M; Wiester, Rebecca T; Feldman, Kenneth W

    2015-03-01

    Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. PMID:25687148

  17. Institutional Protocol to Manage Consanguinity Detected by Genetic Testing in Pregnancy in a Minor

    PubMed Central

    Chen, Laura P.; Beck, Anita E.; Tsuchiya, Karen D.; Chow, Penny M.; Mirzaa, Ghayda M.; Wiester, Rebecca T.

    2015-01-01

    Single-nucleotide polymorphism arrays and other types of genetic tests have the potential to detect first-degree consanguinity and uncover parental rape in cases of minor teenage pregnancy. We present 2 cases in which genetic testing identified parental rape of a minor teenager. In case 1, single-nucleotide polymorphism array in a patient with multiple developmental abnormalities demonstrated multiple long stretches of homozygosity, revealing parental rape of a teenage mother. In case 2, a vague maternal sexual assault history and diagnosis of Pompe disease by direct gene sequencing identified parental rape of a minor. Given the medical, legal, and ethical implications of such revelations, a protocol was developed at our institution to manage consanguinity identified via genetic testing. PMID:25687148

  18. 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

  19. 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.

  20. Ascorbic acid contents of Pakistani fruits and vegetables.

    PubMed

    Iqbal, M Perwaiz; Kazim, Syed Faraz; Mehboobali, Naseema

    2006-10-01

    Fresh fruits and vegetables are good sources of vitamin C which is known for its antioxidant and immune-enhancing effects. The objective of this study was to determine ascorbic acid (vitamin C) contents of regularly consumed fruits and vegetables available in Pakistani markets. Most commonly used fresh fruits and vegetables were homogenized in 5% trichloroacetic acid, and ascorbic acid contents in the extracts were determined using a spectrophotometric method. Banana, custard apple, orange, lemon, guava and papaya were found to be very rich in ascorbic acid. Among vegetables, capsicum (green sweet pepper), cauliflower, bittergourd, roundgourd, beetroot, spinach, cabbage and radish contained high concentrations of ascorbic acid. Chikoo, grapes, pear, apricot, peach, carrot, cucumber, lettuce and "kakri" were found to be poor sources of ascorbic acid. Several Pakistani fruits and vegetables (pear, melon, onion, sweet green pepper, spinach, cucumber) had ascorbic acid values similar to those reported by US Department of Agriculture in these fruits and vegetables in USA. However, wide differences in vitamin C contents were also observed in certain other fruits and vegetables from these two countries. This indicates that regional varieties of fruits and vegetables could vary in their ascorbic acid contents. Since subclinical deficiency of vitamin C appears to be quite common in developing countries like Pakistan, there is a need to develop awareness among masses to consume fresh fruits and vegetables with high contents of vitamin C. PMID:17105704

  1. 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. PMID:21153962

  2. Genetic polymorphisms in Pakistani women with polycystic ovary syndrome.

    PubMed

    Liaqat, Irfana; Jahan, Nusrat; Krikun, Graciela; Taylor, Hugh S

    2015-03-01

    Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility. Although the genetic basis of PCOS is not well understood, it is a common metabolic and endocrine disorder. This study investigates the possible genomic variants associated with PCOS in Pakistani women from the Punjab region. DNA samples from 96 patients with genetically unrelated PCOS and 96 controls were analyzed by direct sequencing to determine the polymorphisms of different loci on follicle-stimulating hormone receptor (fshr), follicle-stimulating hormone β (fshrβ), luteinizing hormone chorionic gonadotropin (lhcgr), luteinizing hormone β (lhβ), estrogen receptor α (esr1), and estrogen receptor β (esr2) genes. Significant associations were observed within the genotype frequencies, allele frequencies, and multi-single-nucleotide polymorphism (SNP) haplotype analysis of most polymorphisms studied. This study identified new SNPs at positions 605+52 Del/T in lhcgr genes occurring in this particular subpopulation. The strong r (2) value suggests that polymorphisms in the fshr and esr1 genes were in linkage disequilibrium. Our study provides evidence of statistically significant associations between susceptibility to PCOS in Pakistani women and the gene polymorphisms mentioned earlier. This suggests that the susceptible loci for PCOS lie within or very close to the chromosomal regions spanning these genes. PMID:25100445

  3. 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

  4. 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.

  5. 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

  6. Limb-girdle muscular dystrophy 2I: phenotypic variability within a large consanguineous Bedouin family associated with a novel FKRP mutation.

    PubMed

    Harel, Tamar; Goldberg, Yael; Shalev, Stavit A; Chervinski, Ilana; Ofir, Rivka; Birk, Ohad S

    2004-01-01

    Limb-girdle muscular dystrophies (LGMDs) represent a group of diseases characterized mainly by muscle wasting of the upper and lower limbs, with a wide range of clinical severity. The clinical heterogeneity is paralleled by molecular heterogeneity; each of the 10 forms of autosomal-recessive LGMD recognized to date is caused by mutations in a distinct gene. In a large consanguineous Bedouin tribe living in northern Israel, 15 individuals affected by LGMD demonstrate an autosomal recessive pattern of inheritance. A genome-wide screen followed by fine mapping in this family revealed linkage to a region on chromosome 19 harboring the fukutin-related protein gene (FKRP), with a maximal LOD score of 4.8 for D19S902. FKRP, encoding a putative glycosyltransferase, has been implicated in causing congenital muscular dystrophy 1C (MDC1C), and has recently been shown to be mutated in LGMD2I. We identified a novel missense mutation in exon 4 of the FKRP gene in all the patients studied. Although all affected individuals were homozygous for the same mutation, a marked phenotypic variability was apparent within the family. This finding may suggest a role of modifier genes and environmental factors in LGMD2I. Moreover, the demonstration that an identical, novel mutation in the FKRP gene can cause a muscle disease of either a congenital onset or of a later onset within a single family provides clinical support to the molecular evidence, suggesting that MDC1C and LGMD2I are overlapping ends of one and the same entity. PMID:14523375

  7. 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…

  8. 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)…

  9. 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

  10. 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

  11. The alkylglycerol monooxygenase (AGMO) gene previously involved in autism also causes a novel syndromic form of primary microcephaly in a consanguineous Saudi family.

    PubMed

    Alrayes, Nuha; Mohamoud, Hussein Sheikh Ali; Ahmed, Saleem; Almramhi, Mona Mohammad; Shuaib, Taghreed Mohammad; Wang, Jun; Al-Aama, Jumana Yousuf; Everett, Kate; Nasir, Jamal; Jelani, Musharraf

    2016-04-15

    Autosomal recessive primary microcephaly (MCPH) refers to a genetically heterogeneous group of neurodevelopmental disorders in which patients exhibit a marked decrease in occipitofrontal head circumference at birth and a variable degree of intellectual disability. To date, 18 genes have been reported for MCPH worldwide. We enrolled a consanguineous family from Saudi Arabia presenting with primary microcephaly, developmental delay, short stature and intellectual disability. Whole exome sequencing (WES) with 100× coverage was performed on two affected siblings after defining common regions of homozygosity through genome-wide single nucleotide polymorphism (SNP) microarray genotyping. WES data analysis, confirmed by subsequent Sanger sequence validation, identified a novel homozygous deletion mutation (c.967delA; p.Glu324Lysfs12*) in exon 10 of the alkylglycerol monooxygenase (AGMO) gene on chromosome 7p21.2. Population screening of 178 ethnically matched control chromosomes and consultation of the Exome Aggregation Consortium database, containing 60,706 individuals' exomes worldwide, confirmed that this mutation was not present outside the family. To the best of our knowledge, this is the first evidence of an AGMO mutation underlying primary microcephaly and intellectual disability in humans. Our findings further expand the genetic heterogeneity of MCPH in familial cases. PMID:27000257

  12. 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

  13. 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

  14. 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

  15. 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

  16. Chance for India to stop the Pakistani bomb

    SciTech Connect

    Spector, L.S.

    1987-11-01

    India would be far better off it, by adopting cautious restraints on its own nuclear activities, it could obtain firm limits on Pakistan's. Moreover, since the US has been long seeking such restraints from India, New Delhi might be able to strike a bargain under which the United States, in return for India's gesture, would withhold the sale of certain conventional weapon systems to Pakistan that India finds threatening. Thus India could improve its position on both the nuclear and conventional fronts. In November 1986, Brazil invited Argentine nuclear technicians to visit a key classified nuclear installation in Sao Paulo. This July, Argentina reciprocated by permitting Brazilian President Jose Sarney to visit its most sensitive nuclear facility. These events demonstrate that, with far-sighted statesmanship, regional nuclear rivalries need not be irreversible. Indo-Pakistani nuclear tensions could be greatly eased if Prime Minister Gandhi and President Zia seize the opportunity now at hand.

  17. 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.

  18. Geomorphological origin of recession curves

    NASA Astrophysics Data System (ADS)

    Biswal, Basudev; Marani, Marco

    2010-12-01

    We identify a previously undetected link between the river network morphology and key recession curves properties through a conceptual-physical model of the drainage process of the riparian unconfined aquifer. We show that the power-law exponent, α, 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. Using Digital Terrain Models and daily discharge observations from 67 US basins we find that geomorphologic α estimates match well the values obtained from recession curves analyses. Finally, we argue that the link between recession flows and network morphology points to an important role of low-flow discharges in shaping the channel network.

  19. 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

  20. 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

  1. Nonsense mutations in the hairless gene underlie APL in five families of Pakistani origin

    PubMed Central

    Kim, Hyunmi; Wajid, Muhammad; Kraemer, Liv; Shimomura, Yutaka; Christiano, Angela M.

    2012-01-01

    (1) Background Atrichia with papular lesions (APL) is a rare autosomal recessive form of inherited alopecia. Affected individuals present with a distinct pattern of total hair loss on the scalp, axilla and body shortly after birth and are essentially devoid of eyelashes and eyebrows. This form of hair loss is irreversible and the histology is consistent with an absence of mature hair follicles. In addition to total atrichia, APL patients also present with papules and follicular cysts filled with cornified material. Mutations in the Hairless (HR) gene have been shown to underlie APL. (2) Objective Here, we studied five unrelated large Pakistani families with clinical manifestations of APL. (3) Methods Based on previous reports of HR mutations in APL, we performed direct DNA sequencing analysis. (4) Results DNA sequencing of the HR gene in APL patients revealed three novel nonsense mutations in five unrelated families. All affected individuals were homozygous for a nonsense mutation due to C-to-T transitions at different positions in the amino acid sequence. Two families carry the mutation Q323X (CAG-TAG) in exon 3, two families harbor the mutation Q502X (CAG-TAG) in exon 6, and one family had a mutation at R940X (CGA-TGA) in exon 14. Haplotype analysis revealed that all affected individuals of both APL1 and APL16 families were homozygous for the same haplotype, and likewise, the mutation in families APL2 and APL19 was on the the same haplotype. (5) Conclusions We report three novel nonsense mutations in the HR gene in APL. Two of the newly identified mutations, Q323X and Q502X, were found to be shared between unrelated families and marker analysis confirmed an identical homozygous haplotype for APL1 and APL16, and for APL2 and APL19. These findings suggest that Q323X and Q502X did not arise independently, but instead appear to have been propagated in the population. Collectively, these findings contribute further evidence for the involvement of hairless mutations in

  2. In-silico analysis of putative HCV epitopes against Pakistani human leukocyte antigen background: An approach towards development of future vaccines for Pakistani population.

    PubMed

    Ashraf, Naeem Mahmood; Bilal, Muhammad; Mahmood, Malik Siddique; Hussain, Aadil; Mehboob, Muhammad Zubair

    2016-09-01

    Mounting burden of HCV-infected individuals and soaring cost of treatment is a serious source of unease for developing countries. Numbers of various approaches have been anticipated to develop a vaccine against HCV but the majority of them proved ineffective. Development of vaccine by considering geographical distribution of HCV genotypes and host genetics shows potential. In this research article, we have tried to predict most putative HCV epitopes which are efficiently restricted by most common HLA alleles in Pakistani population through different computational algorithms. Thirteen selected, experimentally identified epitopes sequences were used to derived consensus sequences in all genotypes of HCV. Obtained consensus sequences were used to predict their binding affinities with most prevalent HLA alleles in Pakistani population. Two Class-I epitopes from NS4B region, one from Class-I epitope from NS5A and one Class-II epitope from NS3 region showed effective binding and proved to be highly putative to boost immune response. A cocktail of these four have been checked for population coverage and they gave 75.53% for Pakistani Asian and 70.77% for Pakistani Mixed populations with no allergenic response. Computational algorithms are robust way to shortlist potential candidate epitopes for vaccine development but further, in vivo and in-vitro studies are required to confirm their immunogenic properties. PMID:27166094

  3. Tuberous sclerosis complex: neonatal deaths in three of four children of consanguineous, non-expressing parents.

    PubMed

    Ruggieri, M; Carbonara, C; Magro, G; Migone, N; Grasso, S; Tinè, A; Pavone, L; Gomez, M R

    1997-03-01

    We describe here four sibs, born to consanguineous, healthy, asymptomatic parents. Three of these infants had a rapidly fatal course in the neonatal period; death was attributed to congestive heart failure with radiographic evidence of cardiomegaly in all of them. Necropsy was done in only one of them and showed the typical findings of tuberous sclerosis complex (TSC) in the central nervous system (CNS), kidneys, heart, and liver. The fourth sib, currently 2 years old, also has typical signs of TSC, namely hypomelanotic skin macules and calcified subependymal nodules. Both parents and a living maternal grandmother had appropriate examination, which included skin inspection under Wood's lamp, dental examination, fundoscopy, echocardiography, abdominal and renal ultrasound, and head CT and MRI scans, and no signs of TSC were found in either parent or in the only living grandmother. By history alone there is no other relative with signs or symptoms suggestive of TSC. Linkage analysis and loss of heterozygosity (LOH) investigations on a variety of lesions obtained from postmortem and tissue or blood specimens from all available family members studied failed to identify a microdeletion in the chromosomal regions where TSC genes are located. It is very unusual that in a single TSC family there were three consecutive neonatal deaths, and very likely that all had cardiac rhabdomyomas. Moreover, to the best of our knowledge, there are no previous reports of TSC families with more than one affected sib, unusually severe manifestations of the disease, and completely normal, consanguineous parents. PMID:9132502

  4. The trauma of a recession.

    PubMed

    Murphy, S M; Kieran, I; Shaughnessy, M O

    2011-09-01

    Employment in construction in Ireland fell by 10% from nearly 282,000 in the second quarter of 2007 to 255,000 in the same period of 2008. Our study looks at the differences in soft tissue upper limb trauma dynamics of a pre- and post-recession Ireland. Construction accounted for 330 patients (27%) of all hand injuries in 2006, but only 18 (3%) in 2009. Our data shows a significant drop in hand injuries related to the construction industry, and more home/DIY cases and deliberate self-harm presenting in their stead. PMID:21431394

  5. TRAPPC9-related autosomal recessive intellectual disability: report of a new mutation and clinical phenotype.

    PubMed

    Marangi, Giuseppe; Leuzzi, Vincenzo; Manti, Filippo; Lattante, Serena; Orteschi, Daniela; Pecile, Vanna; Neri, Giovanni; Zollino, Marcella

    2013-02-01

    Intellectual disability (ID) with autosomal recessive (AR) inheritance is believed to be common; however, very little is known about causative genes and genotype-phenotype correlations. The broad genetic heterogeneity of AR-ID, and its usually nonsyndromic nature make it difficult to pool multiple pedigrees with the same underlying genetic defect to achieve consistent nosology. Nearly all autosomal genes responsible for recessive cognitive disorders have been identified in large consanguineous families from the Middle East, and nonsense mutations in TRAPPC9 have been reported in a total of 5. Although several recurrent phenotypic abnormalities are described in some of these patients, the associated phenotype is usually referred to as nonsyndromic. By means of single-nucleotide polymorphism-array first and then by exome sequencing, we identified a new pathogenic mutation in TRAPPC9 in two Italian sisters born to healthy and apparently nonconsanguineous parents. It consists of a homozygous splice site mutation causing exon skipping with frameshift and premature termination, as confirmed by mRNA sequencing. By detailed phenotypic analysis of our patients, and by critical literature review, we found that homozygous TRAPPC9 loss-of-function mutations cause a distinctive phenotype, characterized by peculiar facial appearance, obesity, hypotonia (all signs resembling a Prader-Willi-like phenotype), moderate-to-severe ID, and consistent brain abnormalities. PMID:22549410

  6. 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

  7. 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. PMID:27230853

  8. 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.

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

    PubMed Central

    Brune, W.; Weber, R. G.; Saul, B.; von Knebel Doeberitz, M.; Grond-Ginsbach, C.; Kellerman, K.; Meinck, H. M.; Becker, C. M.

    1996-01-01

    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(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 spd-ot), the loss of the GlyR alpha 1 subunit is effectively compensated in man. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:8651283

  10. Mutations in CERS3 cause autosomal recessive congenital ichthyosis in humans.

    PubMed

    Radner, Franz P W; Marrakchi, Slaheddine; Kirchmeier, Peter; Kim, Gwang-Jin; Ribierre, Florence; Kamoun, Bourane; Abid, Leila; Leipoldt, Michael; Turki, Hamida; Schempp, Werner; Heilig, Roland; Lathrop, Mark; Fischer, Judith

    2013-06-01

    Autosomal recessive congenital ichthyosis (ARCI) is a rare genetic disorder of the skin characterized by abnormal desquamation over the whole body. In this study we report four patients from three consanguineous Tunisian families with skin, eye, heart, and skeletal anomalies, who harbor a homozygous contiguous gene deletion syndrome on chromosome 15q26.3. Genome-wide SNP-genotyping revealed a homozygous region in all affected individuals, including the same microdeletion that partially affects two coding genes (ADAMTS17, CERS3) and abolishes a sequence for a long non-coding RNA (FLJ42289). Whereas mutations in ADAMTS17 have recently been identified in autosomal recessive Weill-Marchesani-like syndrome in humans and dogs presenting with ophthalmologic, cardiac, and skeletal abnormalities, no disease associations have been described for CERS3 (ceramide synthase 3) and FLJ42289 so far. However, analysis of additional patients with non-syndromic ARCI revealed a splice site mutation in CERS3 indicating that a defect in ceramide synthesis is causative for the present skin phenotype of our patients. Functional analysis of patient skin and in vitro differentiated keratinocytes demonstrated that mutations in CERS3 lead to a disturbed sphingolipid profile with reduced levels of epidermis-specific very long-chain ceramides that interferes with epidermal differentiation. Taken together, these data present a novel pathway involved in ARCI development and, moreover, provide the first evidence that CERS3 plays an essential role in human sphingolipid metabolism for the maintenance of epidermal lipid homeostasis. PMID:23754960

  11. 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…

  12. Rickets and Osteomalacia in the Glasgow Pakistani Community, 1961-71

    PubMed Central

    Ford, J. A.; Colhoun, E. M.; McIntosh, W. B.; Dunnigan, M. G.

    1972-01-01

    The prevalence of vitamin D deficiency was reassessed in April and May 1971, 10 years after the discovery of widespread late rickets and osteomalacia in the Glasgow Pakistani community. Evidence of vitamin D deficiency was found in 28 out of 115 adults and children examined (24%). Children at the age of puberty were most severely affected by rickets, whereas most infants and younger children in the survey were protected by vitamin D supplements. Mild biochemical osteomalacia was common in Pakistani women. A total of 21 Pakistani and Indian children with rickets were admitted to Glasgow hospitals during 1968-70. These comprised 10 children with infantile rickets and 11 with late rickets. Four of the latter group required osteotomy for severe rachitic deformity. Late rickets and osteomalacia in Pakistani and Indian immigrants are not primarily due to nutritional deficiency of vitamin D, though the high phytate content of their diet may be of aetiological importance. A combination of environmental, social, and endogenous factors, the relative importance of which is not at present clear, may also be involved. Advice on the prophylaxis of vitamin D deficiency should be given to all Pakistani and Indian communities in the United Kingdom. PMID:5031709

  13. 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

  14. Does Gingival Recession Require Surgical Treatment?

    PubMed

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

    2015-10-01

    Gingival recession represents a clinical condition in adults frequently encountered in the general dental practice. Clinicians often face dilemmas of whether or not to treat such a condition surgically. 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 the limited understanding of the factors that guide the treatment of gingival recession. Understanding the cause, prognosis, and treatment of gingival recession continues to offer many unanswered questions and challenges in periodontics as we strive to provide the best care possible for our patients. PMID:26427577

  15. Oligohydramnios in a pregnant Pakistani woman with Plasmodium vivax malaria

    PubMed Central

    2014-01-01

    In the Western world, the diagnosis and management of Plasmodium vivax malaria in pregnant women can be challenging, and the pathogenesis of adverse outcomes for both the mother and the foetus is still poorly known. The authors describe the case of a 29-year-old Pakistani woman at the 29th week of her second pregnancy, who was admitted to the Hospital following the abrupt onset of fever. At the time of admission, she had been living in Italy without travelling to any malaria-endemic areas for eight months. She was diagnosed with vivax malaria after a thin blood smear revealed the presence of plasmodial trophozoites and gametocytes and treated accordingly. Due to the onset of oligohydramnios, she underwent caesarian section at the 31st week of pregnancy with no further complications. Histological examination of the placenta showed no evidence of plasmodial infection, but was inconclusive. It is unclear whether oligohydramnios is a complication of pregnancy-related Plasmodium vivax malaria. Given the long latency of hypnozoites, every febrile pregnant patient with a previous stay in an endemic area should be screened for malaria with a thick and a thin blood smear. PMID:24758193

  16. 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

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

    PubMed

    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

    2015-07-01

    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

  18. 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

  19. The tumour suppressor gene WWOX is mutated in autosomal recessive cerebellar ataxia with epilepsy and mental retardation

    PubMed Central

    Mallaret, Martial; Synofzik, Matthis; Lee, Jaeho; Sagum, Cari A.; Mahajnah, Muhammad; Sharkia, Rajech; Drouot, Nathalie; Renaud, Mathilde; Klein, Fabrice A. C.; Anheim, Mathieu; Tranchant, Christine; Mignot, Cyril; Mandel, Jean-Louis; Bedford, Mark; Bauer, Peter; Salih, Mustafa A.; Schüle, Rebecca; Schöls, Ludger; Aldaz, C. Marcelo

    2014-01-01

    We previously localized a new form of recessive ataxia with generalized tonic-clonic epilepsy and mental retardation to a 19 Mb interval in 16q21-q23 by homozygosity mapping of a large consanguineous Saudi Arabian family. We now report the identification by whole exome sequencing of the missense mutation changing proline 47 into threonine in the first WW domain of the WW domain containing oxidoreductase gene, WWOX, located in the linkage interval. Proline 47 is a highly conserved residue that is part of the WW motif consensus sequence and is part of the hydrophobic core that stabilizes the WW fold. We demonstrate that proline 47 is a key amino acid essential for maintaining the WWOX protein fully functional, with its mutation into a threonine resulting in a loss of peptide interaction for the first WW domain. We also identified another highly conserved homozygous WWOX mutation changing glycine 372 to arginine in a second consanguineous family. The phenotype closely resembled the index family, presenting with generalized tonic-clonic epilepsy, mental retardation and ataxia, but also included prominent upper motor neuron disease. Moreover, we observed that the short-lived Wwox knock-out mouse display spontaneous and audiogenic seizures, a phenotype previously observed in the spontaneous Wwox mutant rat presenting with ataxia and epilepsy, indicating that homozygous WWOX mutations in different species causes cerebellar ataxia associated with epilepsy. PMID:24369382

  20. Only a Touch of the Flu? The Simultaneous Manifestation of Acute Necrotizing Encephalopathy in Two Consanguineous Patients

    PubMed Central

    Bloch, C.; Suter, B.; Fischmann, A.; Gensicke, H.; Rüegg, S.; Weisser, M.

    2015-01-01

    This case report describes the simultaneous manifestation of acute necrotizing encephalopathy in 2 consanguineous patients after infection with influenza B based on the autosomal dominant missense mutation of the RANBP2-gene. Differential diagnosis of acute encephalopathy, clinical and radiological clues, and treatment strategies are outlined. PMID:26110162

  1. Rare CFTR mutation 1525-1G>A in a Pakistani patient.

    PubMed

    Wahab, Abdul; Al Thani, G; Dawod, S T; Kambouris, M; Al Hamed, M

    2004-04-01

    Cystic fibrosis (CF) is rare in non-Caucasian populations, and in such populations little is known about the spectrum of mutations and polymorphisms in the cystic fibrosis transmembrane conductance (CFTR) gene. We report the detection of a very rare CFTR mutation 1525-1G>A in intron 9 in a 5-year-old Pakistani child with typical clinical features of CF. It remains to be seen whether mutation 1525-1G>A is characteristic of Pakistani ethnicity with CF or associated with severe phenotypic features. PMID:15088804

  2. XRCC1 and XPD DNA repair gene polymorphisms: A potential risk factor for glaucoma in the Pakistani population

    PubMed Central

    Yousaf, Sajeela; Khan, Muhammad Imran; Micheal, Shazia; Akhtar, Farah; Ali, Syeda Hafiza Benish; Riaz, Moeen; Ali, Mahmood; Lall, Pramila; Waheed, Nadia Khalida; den Hollander, Anneke I.; Ahmed, Asifa

    2011-01-01

    Purpose The present study was designed to determine the association of polymorphisms of the DNA repair genes X-ray cross-complementing group 1 (XRCC1) (c.1316G>A [rs25487]) and xeroderma pigmentosum complementation group D (XPD) (c.2298A>C [rs13181]) with primary open-angle glaucoma (POAG) and primary closed-angle glaucoma (PCAG). Methods In this prospective case-control study, polymerase chain reaction-restriction fragment length polymorphism analysis was used to study the association of XRCC1 and XPD with 160 POAG patients, 163 PCAG patients, and 193 unaffected controls. Results XRCC1 rs25487 was found to be significantly associated specifically with male POAG patients (χ2=13.2 [p=0.001]), only for the dominant model (odds ratio [OR]=2.65 [95% confidence interval [CI]=1.44–4.85], p<0.005). In addition XPD rs13181 was also found to be associated with male POAG patients (χ2=12.1 [p<0.005]), for both dominant (OR=2.44 [95% CI=1.33–4.47], p<0.005) as well as recessive model (OR=3.62 [95% CI=1.45–9.01], p<0.01). Combined genotypes of both the genes revealed that the heterozygote AC/GA was significantly associated with the male POAG patients (z=3.00 [p<0.001]). The AA/GG genotype was present at a higher frequency in the male controls and the AA/GA in the female controls and could thus have a protective role in males and females, respectively. Conclusions We postulate that defects in the DNA repair genes XRCC1 and XPD may possibly be associated with the progression of POAG in male patients of Pakistani origin. PMID:21617750

  3. Syndrome Keratitis-Ichtyosis-Deafness (KID) chez un enfant togolais issu d'un mariage consanguin

    PubMed Central

    Kombaté, Koussak; Saka, Bayaki; Landoh, Dadja Essoya; Mouhari-Toure, Abass; Akakpo, Séfako; Belei, Eric; Gnassingbé, Wanguena; Djibril, Mohaman Awalou; Tchangaï-Walla, Kissem; Pitché, Palokinam

    2015-01-01

    Le syndrome KID est une affection génétique rare associant kératite, ichtyose et surdité. Nous rapportons un cas dont la surdité s'est compliquée de mutisme chez un enfant togolais issu d'un mariage consanguin.Il s'agissait d'une fillette de 9 ans admise en dermatologie pour une peau sèche et une kératodermie palmoplantaire évoluant depuis l'enfance, une surdité sévère et un mutisme total évoluant depuis la naissance. Il n'y avait pas d'histoire familiale connue de syndrome KID. Les parents de cet enfant sont des cousins germains. A l'examen, on notait une kératodermie palmoplantaire typique en cuir grossier, une peau sèche ichtyosiforme finement squameuse avec un aspect pachydermique aux genoux et un aspect arlequin aux jambes. L'examen ophtalmologique avait noté une blépharo-conjonctivite, une xérophtalmie, une photophobie et une absence de sourcils. L'examen ORL avait objectivé une hypotrophie des pavillons des oreilles, une surdité sévère et un mutisme total. La particularité de cette observation réside dans la sévérité de l'atteinte auditive qui s'est compliquée de mutisme. Notre enfant étant née de parents consanguins sains, sans histoire familiale de KID, nous pensons que le mode de transmission est probablement sporadique. Une étude moléculaire du cas index et de ses parents, non réalisée à cause de notre plateau technique limité aurait pu le confirmer. PMID:26664520

  4. A hypofunctional PAX1 mutation causes autosomal recessively inherited otofaciocervical syndrome.

    PubMed

    Pohl, Esther; Aykut, Ayca; Beleggia, Filippo; Karaca, Emin; Durmaz, Burak; Keupp, Katharina; Arslan, Esra; Palamar, Melis; Onay, Melis Palamar; Yigit, Gökhan; Özkinay, Ferda; Wollnik, Bernd

    2013-11-01

    Otofaciocervical syndrome (OFCS) is an autosomal recessively inherited disorder characterized by facial dysmorphism, external ear anomalies with preauricular pits and hearing impairment, branchial cysts or fistulas, anomalies of the vertebrae and the shoulder girdle, and mild intellectual disability. In a large consanguineous family with OFCS from Turkey, we performed whole-exome sequencing (WES) of a single pooled DNA sample of four affected individuals. Filtering for variants with a percentage of alternate reads ≥ 90 % and a coverage of at least five reads identified only a single novel homozygous variant, c.497G>T, located in PAX1 that co-segregated with the disease in the family. PAX1 encodes a transcription factor with a critical role in pattern formation during embryogenesis in vertebrates. The mutation is predicted to substitute the glycine at position 166 to valine (p.G166V) within the highly conserved paired-box domain of the PAX1 protein. We performed a dual luciferase reporter assay to examine the transactivation of a regulatory sequence in the Nkx3-2 promoter region, which is a direct target of mouse Pax1 transcriptional regulation. We observed a significantly reduced transactivation in HEK293T cells overexpressing Pax1(G157V) in comparison to Pax1(WT) expressing cells, indicating a reduced DNA-binding affinity of the mutant protein. Taken together, our results show that the strategy of pooling DNA is a powerful, cost-effective application for WES in consanguineous families and establish PAX1 as a new disease-causing gene for OFCS and as part of the EYA-DACH-SIX-PAX network, important in early embryogenesis. PMID:23851939

  5. Mutations in zinc finger 407 [ZNF407] cause a unique autosomal recessive cognitive impairment syndrome

    PubMed Central

    2014-01-01

    Background A consanguineous Arab family is affected by an apparently novel autosomal recessive disorder characterized by cognitive impairment, failure-to-thrive, hypotonia and dysmorphic features including bilateral ptosis and epicanthic folds, synophrys, midface hypoplasia, downturned mouth corners, thin upper vermillion border and prominent ears, bilateral 5th finger camptodactyly, bilateral short 4th metatarsal bones, and limited knee mobility bilaterally. Methods The family was studied by homozygosity mapping, candidate gene mutation screening and whole Exome Next Generation Sequencing of a single affected member to identify the offending gene and mutation. The mutated gene product was studied by structural bioinformatics methods. Results A damaging c.C5054G mutation affecting an evolutionary highly conserved amino acid p.S1685W was identified in the ZNF407 gene at 18q23. The Serine to Tryptophane mutation affects two of the three ZNF407 isoforms and is located in the last third of the protein, in a linker peptide adjoining two zinc-finger domains. Structural analyses of this mutation shows disruption of an H-bond that locks the relative spatial position of the two fingers, leading to a higher flexibility of the linker and thus to a decreased probability of binding to the target DNA sequence essentially eliminating the functionality of downstream domains and interfering with the expression of various genes under ZNF407 control during fetal brain development. Conclusions ZNF407 is a transcription factor with an essential role in brain development. When specific and limited in number homozygosity intervals exist that harbor the offending gene in consanguineous families, Whole Exome Sequencing of a single affected individual is an efficient approach to gene mapping and mutation identification. PMID:24907849

  6. 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

  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. Recess for Elementary School Students. Position Statement

    ERIC Educational Resources Information Center

    National Association for Sport and Physical Education, 2006

    2006-01-01

    It is the position of the National Association for Sport and Physical Education (NASPE) that all elementary school children should be provided with at least one daily period of recess of at least 20 minutes in length. Recess is an essential component of a comprehensive school physical activity program and of the total education experience for…

  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. PMID:23277311

  11. Autosomal recessive mental retardation: homozygosity mapping identifies 27 single linkage intervals, at least 14 novel loci and several mutation hotspots.

    PubMed

    Kuss, Andreas Walter; Garshasbi, Masoud; Kahrizi, Kimia; Tzschach, Andreas; Behjati, Farkhondeh; Darvish, Hossein; Abbasi-Moheb, Lia; Puettmann, Lucia; Zecha, Agnes; Weissmann, Robert; Hu, Hao; Mohseni, Marzieh; Abedini, Seyedeh Sedigheh; Rajab, Anna; Hertzberg, Christoph; Wieczorek, Dagmar; Ullmann, Reinhard; Ghasemi-Firouzabadi, Saghar; Banihashemi, Susan; Arzhangi, Sanaz; Hadavi, Valeh; Bahrami-Monajemi, Gholamreza; Kasiri, Mahboubeh; Falah, Masoumeh; Nikuei, Pooneh; Dehghan, Atefeh; Sobhani, Masoumeh; Jamali, Payman; Ropers, Hans Hilger; Najmabadi, Hossein

    2011-02-01

    Mental retardation (MR) has a worldwide prevalence of around 2% and is a frequent cause of severe disability. Significant excess of MR in the progeny of consanguineous matings as well as functional considerations suggest that autosomal recessive forms of MR (ARMR) must be relatively common. To shed more light on the causes of autosomal recessive MR (ARMR), we have set out in 2003 to perform systematic clinical studies and autozygosity mapping in large consanguineous Iranian families with non-syndromic ARMR (NS-ARMR). As previously reported (Najmabadi et al. in Hum Genet 121:43-48, 2007), this led us to the identification of 12 novel ARMR loci, 8 of which had a significant LOD score (OMIM: MRT5-12). In the meantime, we and others have found causative gene defects in two of these intervals. Moreover, as reported here, tripling the size of our cohort has enabled us to identify 27 additional unrelated families with NS-ARMR and single-linkage intervals; 14 of these define novel loci for non-syndromic ARMR. Altogether, 13 out of 39 single linkage intervals observed in our cohort were found to cluster at 6 different loci on chromosomes, i.e., 1p34, 4q27, 5p15, 9q34, 11p11-q13 and 19q13, respectively. Five of these clusters consist of two significantly overlapping linkage intervals, and on chr 1p34, three single linkage intervals coincide, including the previously described MRT12 locus. The probability for this distribution to be due to chance is only 1.14 × 10(-5), as shown by Monte Carlo simulation. Thus, in contrast to our previous conclusions, these novel data indicate that common molecular causes of NS-ARMR do exist, and in the Iranian population, the most frequent ones may well account for several percent of the patients. These findings will be instrumental in the identification of the underlying genes. PMID:21063731

  12. 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.

  13. 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…

  14. 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.

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. The Impact of Educational Change on School Leaders: Experiences of Pakistani School Leaders

    ERIC Educational Resources Information Center

    Razzaq, Jamila; Forde, Christine

    2013-01-01

    The Pakistani education system, like many other countries across the world, is going through a phase of concerted change in the first decade of the 21st century and school leaders are expected to play a crucial role in the management of this change programme. This article considers the impact of educational change on a group of school leaders who…

  2. 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,…

  3. 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…

  4. 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…

  5. Event-based Recession Analysis across Scales

    NASA Astrophysics Data System (ADS)

    Chen, B.; Krajewski, W. F.

    2012-12-01

    Hydrograph recessions have long been a window to investigate hydrological processes and their interactions. The authors conducted an exploratory analysis of about 1000 individual hydrograph recessions in a period of around 15 years (1995-2010) from time series of hourly discharge (USGS IDA stream flow data set) at 27 USGS gauges located in Iowa and Cedar River basins with drainage area ranging from 6.7 to around 17000 km2. They calculated recession exponents with the same recession length but different time lags from the hydrograph peak ranging from ~0 to 96 hours, and then plotted them against time lags to construct the evolution of recession exponent. The result shows that, as recession continues, the recession exponent in first increases quickly, then decreases quickly, and finally stays constant. Occasionally and for different reasons, the decreasing portion is missing due to negligible contribution from soil water storage. The increasing part of the evolution of can be related to fast response to rainfall including overland flow and quick subsurface flow through macropores (or tiles), and the decreasing portion can be connected to the delayed soil water response. Lastly, the constant segment can be attributed to the groundwater storage with the slowest response. The points where recession exponent reaches its maximum and begins to plateau are the times that fast response and soil water response end, respectively. The authors conducted further theoretical analysis by combining mathematical derivation and literature results to explain the observed evolution path of the recession exponent . Their results have a direct application in hydrograph separation and important implications for dynamic basin storage-discharge relation analysis and hydrological process understanding across scales.

  6. 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

  7. 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

  8. 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

  9. 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- ...

  10. Graduated recession of the superior oblique muscle.

    PubMed Central

    Caldeira, J A

    1975-01-01

    Recession of the superior oblique was performed bilaterally in 12 patients with the A phenomenon and unilaterally in four patients with vertical imbalance. The results are discussed. Images PMID:1191613

  11. The Great Recession's impact on children.

    PubMed

    Oberg, Charles N

    2011-07-01

    Since that first day of the millennium the United States has experienced two recessions. The first recession began in 2001 and lasted for 10 months. The second, now referred to as the Great Recession, began in December of 2007, was approximately 18 months in duration and was followed by a weak and jobless recovery that has persisted into the second decade of this century. This commentary will examine how low-income children have fared in regard to economic security, food insecurity and housing instability as a result of the Great Recession and recent economic downturn. It concludes with a call to action for a renewed investment in our children through a Children's Recovery and Stimulus Initiative. PMID:21528399

  12. 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.

  13. Missense mutations at homologous positions in the fourth and fifth laminin A G-like domains of eyes shut homolog cause autosomal recessive retinitis pigmentosa

    PubMed Central

    Khan, Muhammad Imran; Collin, Rob W.J.; Arimadyo, Kentar; Micheal, Shazia; Azam, Maleeha; Qureshi, Nadeem; Faradz, Sultana M.H.; den Hollander, Anneke I.; Qamar, Raheel

    2010-01-01

    Purpose To describe two novel mutations in the eyes shut homolog (EYS) gene in two families with autosomal recessive retinitis pigmentosa (arRP) from Pakistan and Indonesia. Methods Genome-wide linkage and homozygosity mapping were performed using single nucleotide polymorphism microarray analysis in affected members of the two arRP families. Sequence analysis was performed to identify genetic changes in protein coding exons of EYS. Results In the Indonesian and Pakistani families, homozygous regions encompassing the EYS gene at 6q12 were identified, with maximum LOD scores of 1.8 and 3.6, respectively. Novel missense variants in the EYS gene (p.D2767Y and p.D3028Y) were found in the Pakistani and Indonesian families, respectively, that co-segregate with the disease phenotype. Interestingly, the missense variants are located at the same homologous position within the fourth and fifth laminin A G-like domains of EYS. Conclusions To date, mostly protein-truncating mutations have been described in EYS, while only few patients have been described with pathogenic compound heterozygous missense mutations. The mutations p.D2767Y and p.D3028Y described in this study affect highly conserved residues at homologous positions in laminin A G-like domains and support the notion that missense mutations in EYS can cause arRP. PMID:21179430

  14. 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

  15. A novel technique for inferior rectus recession

    PubMed Central

    Gokyigit, Birsen; Akar, Serpil; Yilmaz, Omer Faruk

    2014-01-01

    Purpose To introduce a novel technique of inferior rectus recession operation to allow larger amounts of recession without causing lower lid retraction and to compare this method with the results obtained in standard inferior rectus recession. Material and methods This study included 20 patients operated on in the authors’ clinic. The median age of the patients was 24.5±18.6 (4–73) years and the median follow-up was 9.3±11.8 (3–43) months. Ten patients operated on with the standard method were labeled Group 1 and ten patients operated on with the new method were labeled Group 2. Without exceeding 4 mm, inferior rectus recession to the whole muscle was performed in Group 1 patients. Inferior rectus recession was also performed on patients in Group 2 following the new method. Using a spatula, approximately 10% of the muscle surface fibers were detached intact as a thin layer, and the remaining 90% of deeper fibers were recessed 4–8 mm as planned. Patients’ preoperative deviations and lower lid positions were recorded. The same parameters were checked in the first and third month postoperatively. Both groups were evaluated retrospectively by screening their files, and the Mann–Whitney U test was used for statistical evaluation. Results Lower lid retraction was seen in four patients of Group 1. There was no retraction in Group 2. While there was a need to perform additional vertical muscle procedures for vertical deviations and lower lid retractions in Group 1, it was observed that there was no need for additional procedures in Group 2 patients. There was a statistically meaningful difference between the two procedures (P<0.05). Conclusion This novel technique was found to be an effective surgical method for permitting more recession without the risk of lower lid retraction. PMID:24492531

  16. Are we thinking straight about groundwater recession?

    NASA Astrophysics Data System (ADS)

    Cuthbert, M. O.

    2013-12-01

    By exploring what governs the form of groundwater head recession in idealised and real aquifers, it will be shown that the analysis of groundwater recessions is a powerful but underused way of gaining insight into the hydrologic functioning of an aquifer from local to regional scales. It is commonly assumed that groundwater head recession in aquifers will take exponential form. However, here it is demonstrated that ideal regional aquifers should, given enough time between recharge events, actually develop through three distinct phases of recession: (1) in early times the groundwater recession should take an almost straight line form with a rate approximately equal to the long term recharge rate divided by the specific yield. The length of this phase can be estimated from a new analytical expression, which depends on the aquifer diffusivity, length scale and the position of the monitoring point, (2) a transitional phase then leads to, (3) an exponential phase after some critical time which is described by an existing analytical expression which is independent of the position of the monitoring point. Further analysis reveals that major aquifers in a state of periodic quasi-steady state are expected to have rates of net groundwater drainage which deviate little from the average rate of groundwater recharge. To back up these theoretical considerations, a range of real groundwater hydrographs will be presented which demonstrate the characteristic behaviour and interactions of groundwater flow systems interacting at local to regional scales. Where groundwater declines are observed in nature to have a quasi-exponential form, this may be diagnostic of particular types of aquifer properties and/or boundary effects such as: storage changes due to pumping, proximity to drainage boundaries, variations in transmissivity with hydraulic head, and variations in specific yield with depth. Furthermore, 'non-equilibrium' flow at a range of spatial and temporal scales helps explain

  17. 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. PMID:23236289

  18. TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis.

    PubMed

    Cangul, Hakan; Aycan, Zehra; Saglam, Halil; Forman, Julia R; Cetinkaya, Semra; Tarim, Omer; Bober, Ece; Cesur, Yasar; Kurtoglu, Selim; Darendeliler, Feyza; Bas, Veysel; Eren, Erdal; Demir, Korcan; Kiraz, Aslihan; Aydin, Banu K; Karthikeyan, Ambika; Kendall, Michaela; Boelaert, Kristien; Shaw, Nick J; Kirk, Jeremy; Högler, Wolfgang; Barrett, Timothy G; Maher, Eamonn R

    2012-01-01

    Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH. PMID:22876533

  19. 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.

  20. An Autosomal Recessive Form of Bilateral Frontoparietal Polymicrogyria Maps to Chromosome 16q12.2-21

    PubMed Central

    Piao, Xianhua; Basel-Vanagaite, Lina; Straussberg, Rachel; Grant, P. Ellen; Pugh, Elizabeth W.; Doheny, Kim; Doan, Betty; Hong, Susan E.; Shugart, Yin Yao; Walsh, Christopher A.

    2002-01-01

    Polymicrogyria is a cerebral cortical malformation that is grossly characterized by excessive cortical folding and microscopically characterized by abnormal cortical layering. Although polymicrogyria appears to have one or more genetic causes, no polymicrogyria loci have been identified. Here we describe the clinical and radiographic features of a new genetic form of polymicrogyria and localize the responsible gene. We studied two consanguineous Palestinian pedigrees with an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), using linkage analysis. Five affected children had moderate-to-severe mental retardation, developmental delay, and esotropia, and four of the five affected children developed seizures. Brain magnetic-resonance imaging revealed polymicrogyria that was most prominent in the frontal and parietal lobes but involved other cortical areas as well. A genomewide linkage screen revealed a single locus that was identical by descent in affected children in both families and showed a single disease-associated haplotype, suggesting a common founder mutation. The locus for BFPP maps to chromosome 16q12.2-21, with a minimal interval of 17 cM. For D16S514, the maximal pooled two-point LOD score was 3.98, and the maximal multipoint LOD score was 4.57. This study provides the first genetic evidence that BFPP is an autosomal recessive disorder and serves as a starting point for the identification of the responsible gene. PMID:11845408

  1. PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot-Marie-Tooth disease.

    PubMed

    Azzedine, Hamid; Zavadakova, Petra; Planté-Bordeneuve, Violaine; Vaz Pato, Maria; Pinto, Nuno; Bartesaghi, Luca; Zenker, Jennifer; Poirot, Olivier; Bernard-Marissal, Nathalie; Arnaud Gouttenoire, Estelle; Cartoni, Romain; Title, Alexandra; Venturini, Giulia; Médard, Jean-Jacques; Makowski, Edward; Schöls, Ludger; Claeys, Kristl G; Stendel, Claudia; Roos, Andreas; Weis, Joachim; Dubourg, Odile; Leal Loureiro, José; Stevanin, Giovanni; Said, Gérard; Amato, Anthony; Baraban, Jay; LeGuern, Eric; Senderek, Jan; Rivolta, Carlo; Chrast, Roman

    2013-10-15

    Charcot-Marie-Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells. PMID:23777631

  2. Novel mutation in TSPAN12 leads to autosomal recessive inheritance of congenital vitreoretinal disease with intra-familial phenotypic variability.

    PubMed

    Gal, Moran; Levanon, Erez Y; Hujeirat, Yasir; Khayat, Morad; Pe'er, Jacob; Shalev, Stavit

    2014-12-01

    Developmental malformations of the vitreoretinal vasculature are a heterogeneous group of conditions with various modes of inheritance, and include familial exudative vitreoretinopathy (FEVR), persistent fetal vasculature (PFV), and Norrie disease. We investigated a large consanguineous kindred with multiple affected individuals exhibiting variable phenotypes of abnormal vitreoretinal vasculature, consistent with the three above-mentioned conditions and compatible with autosomal recessive inheritance. Exome sequencing identified a novel c.542G > T (p.C181F) apparently mutation in the TSPAN12 gene that segregated with the ocular disease in the family. The TSPAN12 gene was previously reported to cause dominant and recessive FEVR, but has not yet been associated with other vitreoretinal manifestations. The intra-familial clinical variability caused by a single mutation in the TSPAN12 gene underscores the complicated phenotype-genotype correlation of mutations in this gene, and suggests that there are additional genetic and environmental factors involved in the complex process of ocular vascularization during embryonic development. Our study supports considering PFV, FEVR, and Norrie disease a spectrum of disorders, with clinical and genetic overlap, caused by mutations in distinct genes acting in the Norrin/β-catenin signaling pathway. PMID:25250762

  3. PLEKHG5 deficiency leads to an intermediate form of autosomal-recessive Charcot–Marie–Tooth disease

    PubMed Central

    Azzedine, Hamid; Zavadakova, Petra; Planté-Bordeneuve, Violaine; Vaz Pato, Maria; Pinto, Nuno; Bartesaghi, Luca; Zenker, Jennifer; Poirot, Olivier; Bernard-Marissal, Nathalie; Arnaud Gouttenoire, Estelle; Cartoni, Romain; Title, Alexandra; Venturini, Giulia; Médard, Jean-Jacques; Makowski, Edward; Schöls, Ludger; Claeys, Kristl G.; Stendel, Claudia; Roos, Andreas; Weis, Joachim; Dubourg, Odile; Leal Loureiro, José; Stevanin, Giovanni; Said, Gérard; Amato, Anthony; Baraban, Jay; LeGuern, Eric; Senderek, Jan; Rivolta, Carlo; Chrast, Roman

    2013-01-01

    Charcot–Marie–Tooth disease (CMT) comprises a clinically and genetically heterogeneous group of peripheral neuropathies characterized by progressive distal muscle weakness and atrophy, foot deformities and distal sensory loss. Following the analysis of two consanguineous families affected by a medium to late-onset recessive form of intermediate CMT, we identified overlapping regions of homozygosity on chromosome 1p36 with a combined maximum LOD score of 5.4. Molecular investigation of the genes from this region allowed identification of two homozygous mutations in PLEKHG5 that produce premature stop codons and are predicted to result in functional null alleles. Analysis of Plekhg5 in the mouse revealed that this gene is expressed in neurons and glial cells of the peripheral nervous system, and that knockout mice display reduced nerve conduction velocities that are comparable with those of affected individuals from both families. Interestingly, a homozygous PLEKHG5 missense mutation was previously reported in a recessive form of severe childhood onset lower motor neuron disease (LMND) leading to loss of the ability to walk and need for respiratory assistance. Together, these observations indicate that different mutations in PLEKHG5 lead to clinically diverse outcomes (intermediate CMT or LMND) affecting the function of neurons and glial cells. PMID:23777631

  4. 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

  5. Mutations in SNX14 cause a distinctive autosomal-recessive cerebellar ataxia and intellectual disability syndrome.

    PubMed

    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

    2014-11-01

    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

  6. A case report: Autosomal recessive microcephaly caused by a novel mutation in MCPH1 gene.

    PubMed

    Ghafouri-Fard, Soudeh; Fardaei, Majid; Gholami, Milad; Miryounesi, Mohammad

    2015-10-15

    Autosomal Recessive Primary Microcephaly (MCPH-MIM 251200) is distinguished by congenital decrease in occipito-frontal head circumference (OFC) of at least 2 standard deviations (SD) below population average in addition to non-progressive mental retardation, without any prominent neurological disorder. Mutations in MCPH1, which encodes the protein microcephalin have been detected in this disorder. Here we report a consanguineous Iranian family with 2 children affected with microcephaly. Despite the severe mental retardation observed in the male patient, the female patient had normal intelligent with no delay in motor milestones or speech. A novel splice-acceptor site homozygous mutation has been detected in intron 4 of MCPH1 gene (c.322-2A>T) which results in an RNA processing defect with a 15-nucleotide deletion in exon 5 of the mRNA transcript (r.322_336del15, p.R108_Q112del5). This novel mutation has resulted in different phenotypes in affected male and female patients of this family. The sex-specific variations in gene regulation during brain development may partially explain such difference in phenotypes probably in addition to other mechanisms such as modifier genes. PMID:26192461

  7. Mutations in TPRN cause a progressive form of autosomal-recessive nonsyndromic hearing loss.

    PubMed

    Li, Yun; Pohl, Esther; Boulouiz, Redouane; Schraders, Margit; Nürnberg, Gudrun; Charif, Majida; Admiraal, Ronald J C; von Ameln, Simon; Baessmann, Ingelore; Kandil, Mostafa; Veltman, Joris A; Nürnberg, Peter; Kubisch, Christian; Barakat, Abdelhamid; Kremer, Hannie; Wollnik, Bernd

    2010-03-12

    We performed genome-wide homozygosity mapping in a large consanguineous family from Morocco and mapped the autosomal-recessive nonsyndromic hearing loss (ARNSHL) in this family to the DFNB79 locus on chromosome 9q34. By sequencing of 62 positional candidate genes of the critical region, we identified a causative homozygous 11 bp deletion, c.42_52del, in the TPRN gene in all seven affected individuals. The deletion is located in exon 1 and results in a frameshift and premature protein truncation (p.Gly15AlafsX150). Interestingly, the deleted sequence is part of a repetitive and CG-rich motive predicted to be prone to structural aberrations during crossover formation. We identified another family with progressive ARNSHL linked to this locus, whose affected members were shown to carry a causative 1 bp deletion (c.1347delG) in exon 1 of TPRN. The function of the encoded protein, taperin, is unknown; yet, partial homology to the actin-caping protein phostensin suggests a role in actin dynamics. PMID:20170898

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. Number of Pakistani physicians working abroad; do we really need to know?

    PubMed

    Qureshi, Ahmad Zaheer; Rathore, Farooq Azam

    2014-12-01

    There are around 175,600 registered doctors in Pakistan, but limited data is available about Pakistani physicians pursuing medical careers abroad. Additionally, no data is reported about Pakistani physicians who leave the country to pursue medical career overseas, but end up in non-medical professions. We identified two groups of physicians leaving the country: those going abroad for postgraduate training and residency; and those doing so for better career incentives and monetary benefits and to avoid the deteriorating law and order situation and rising hostilities towards doctors in the last few years. Other factors contributing towards physician's migration include poor service structure and career prospects, lack of research funding, increased workload and stressful work environment. Optimal measures need to be taken so that the locally trained doctors can deliver their services where they are needed the most, instead of seeking overseas opportunities. Similarly, volume of expertise may be enhanced by promoting social accountability among Pakistani physicians working abroad and by creating comparable opportunities within the country. PMID:25842588

  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. PMID:22950460

  16. Factors associated with the process of adaptation among Pakistani adolescent females living in United States.

    PubMed

    Khuwaja, Salma A; Selwyn, Beatrice J; Mgbere, Osaro; Khuwaja, Alam; Kapadia, Asha; McCurdy, Sheryl; Hsu, Chiehwen E

    2013-04-01

    This study explored post-migration experiences of recently migrated Pakistani Muslim adolescent females residing in the United States. In-depth, semi-structured interviews were conducted with thirty Pakistani Muslim adolescent females between the ages of 15 and 18 years living with their families in Houston, Texas. Data obtained from the interviews were evaluated using discourse analysis to identify major reoccurring themes. Participants discussed factors associated with the process of adaptation to the American culture. The results revealed that the main factors associated with adaptation process included positive motivation for migration, family bonding, social support networks, inter-familial communication, aspiration of adolescents to learn other cultures, availability of English-as-second-language programs, participation in community rebuilding activities, and faith practices, English proficiency, peer pressure, and inter-generational conflicts. This study provided much needed information on factors associated with adaptation process of Pakistani Muslim adolescent females in the United States. The results have important implications for improving the adaptation process of this group and offer potential directions for intervention and counseling services. PMID:22940911

  17. "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.

  18. A novel locus for autosomal recessive primary torsion dystonia (DYT17) maps to 20p11.22-q13.12.

    PubMed

    Chouery, E; Kfoury, J; Delague, V; Jalkh, N; Bejjani, P; Serre, J L; Mégarbané, A

    2008-10-01

    Primary torsion dystonia is a clinically and genetically heterogeneous group of movement disorders. Fifteen different types of dystonia have been described to date, of whom 14 loci have been mapped, but only seven genes identified. Several different modes of inheritance have been described, including autosomal dominant transmission with reduced penetrance (12 loci), recessive X-linked (one locus), and autosomal recessive transmission (three loci). In this study, we describe the localization of a novel form of autosomal recessive, primary focal torsion dystonia using a genomewide search in a large consanguineous Lebanese family with three affected individuals. Homozygosity mapping with 382 microsatellite markers was conducted. Linkage analysis and haplotype construction allowed us to identify a novel locus designated as DYT17, within a 20.5-Mb interval on chromosome 20. Of the 270 known genes spread on this interval, 27 candidate genes were tested and excluded as responsible for the disease. Fine mapping by identification of other dystonia families linked to chromosome 20 and sequencing of candidate genes in the refined interval is required in order to identify the causative gene in DYT17. PMID:18688663

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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)

  10. The Global Picture. Recession to Recovery

    ERIC Educational Resources Information Center

    Universities UK, 2010

    2010-01-01

    The objectives of this study were to: (1) document government and HE (higher education) sector responses to the recession within a select number of key countries which compete with the UK; and (2) compare these responses and analyse them by theme to draw out any common patterns. The focus of the work was to find, where possible, an evidence base…

  11. 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. PMID:22143980

  12. 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 ...

  13. Cognitive-behavioral treatment of a second-generation child of Pakistani descent: ethnocultural and clinical considerations.

    PubMed

    Mahr, Fauzia; McLachlan, Niel; Friedberg, Robert D; Mahr, Safia; Pearl, Amanda M

    2015-01-01

    Ethnocultural variables in cognitive behavioral therapy (CBT) are gaining an increasing amount of attention. This is a welcome development since cultural responsiveness is a core element in ethical and effective CBT practice. However, the literature is sparse and generally silent regarding CBT with children of Pakistani descent. Accordingly, this case based article attempts to close the knowledge gap by reviewing the extant literature pertaining to the role of religion, help seeking behavior, and emotional expression in Pakistani families. The literature review is followed by a case discussion of an 11 year old second generation Pakistani male living in the United Kingdom who is struggling with posttraumatic stress disorder (PTSD). The case presentation highlights the importance of culturally informed case conceptualization and individually tailored interventions. The case illustrates the way cognitive behavioral psychotherapy balanced empirically based procedures with a sensitive appreciation of cultural context. PMID:23982991

  14. 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…

  15. 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

  16. 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

  17. 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. PMID:26627887

  18. 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

  19. 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

  20. 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

  1. Pharmacokinetics of artemether and dihydroartemisinin in healthy Pakistani male volunteers treated with artemether-lumefantrine

    PubMed Central

    2010-01-01

    Background Artemether-lumefantrine is one of the most widely used anti-malarial drug combinations in the world with excellent tolerability and cure rates in adult and paediatric patients with uncomplicated falciparum malaria. The aim of this study was to evaluate the pharmacokinetics of artemether and its active metabolite, dihydroartemisinin, in healthy Pakistani volunteers. Methods Twelve healthy male Pakistani subjects, aged 20 to 50, were recruited into the study. A fixed oral combination of artemether-lumefantrine (80-480 mg) was given as a single oral dose. Frequent blood samples were collected and artemether and dihydroartemisinin were quantified in human plasma using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. Drug concentration-time data were evaluated with non-compartmental analysis. Results Observed maximum concentrations (mean ± SD) of artemether and dihydroartemisinin were 184 ± 100 ng/mL and 126 ± 46 ng/mL, respectively. These concentrations were reached at 1.56 ± 0.68 hr and 1.69 ± 0.59 hr, respectively, after drug intake. The terminal elimination half-life of artemether and dihydroartemisinin were 2.00 ± 0.71 hr and 1.80 ± 0.31 hr, respectively. Apparent volume of distribution and oral clearance for artemether were estimated to 666 ± 220 L and 257 ± 140 L/hr. The same parameters were estimated to 702 ± 220 L and 269 ± 57 L/hr for dihydroartemisinin. Conclusions The overall pharmacokinetic properties of artemether and dihydroartemisinin in healthy Pakistani subjects are comparable to healthy subjects and patients from other populations. PMID:20932349

  2. Alterations in the RB1 gene in Pakistani patients with retinoblastoma using direct sequencing analysis

    PubMed Central

    Wasim, Muhammad; Afzal, Sibtain; Shahzad, Muhammad Saqib; Ramzan, Shaiqa; Awan, Ali Raza; Anjum, Aftab Ahmed; Ramzan, Khushnooda

    2015-01-01

    Purpose Retinoblastoma (RB) is a rare intraocular malignant tumor of the developing retina with an estimated incidence of 1:20,000 live births in children under the age of 5 years. In addition to the abnormal whitish appearance of the pupil or leukocoria, strabismus has also been reported as a clinical symptom of the disease. RB1 is the first cloned tumor suppressor gene, and mutational inactivation of this gene is responsible for the development of RB during early childhood. The purpose of this study was to identify mutational alterations in the RB1 gene in Pakistani patients with RB. Methods During this study, 70 clinically evaluated patients with RB were recruited from different regions of Pakistan. The cases included 23 sporadic bilateral (32.9%), 34 sporadic unilateral (48.6%), nine familial bilateral (12.8%), and four familial unilateral (5.7%) cases. Constitutional causative mutations in the RB1 gene were screened via direct sequencing of all RB1 exons and their flanking regions. Results In this report, genetic testing resulted in the identification of 18 mutations in 25 patients with RB including six novel RB1 mutations. Of the total mutations identified, 13 (72.22%) were found to be null mutations caused by nine nonsense, three deletions, and one insertion. Two (11.11%) missense, two (11.11%) splice site mutations, and one (5.55%) base substitution in the promoter region were also found. Moreover, ten intronic variants were identified, one of which is novel. Conclusions Molecular screening and identification of these mutations in Pakistani patients with RB provide the mutational variants of the RB1 gene in the Pakistani population. The detection of oncogenic mutations in patients with RB and genetically predisposed individuals is a major step in clinical management, prognosis, follow-up care, accurate genetic counseling, and presymptomatic diagnosis of RB. PMID:26396485

  3. 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. PMID:25481369

  4. Photogrammetric recession measurements of an ablating surface

    NASA Technical Reports Server (NTRS)

    Schairer, Edward T. (Inventor); Heineck, James T. (Inventor)

    2012-01-01

    An instrument and method for measuring the time history of recession of an ablating surface of a test article during testing in a high enthalpy thermal test facility, such as an arcjet. The method advances prior art by providing time-history data over the full ablating surface without targets and without any modifications to the test article. The method is non-intrusive, simple to implement, requires no external light source, and does not interfere with normal operations of the arcjet facility.

  5. 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.

  6. 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.

  7. Semiconductor devices having a recessed electrode structure

    SciTech Connect

    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.

  8. 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

  9. Amalgam use and waste management by Pakistani dentists: an environmental perspective.

    PubMed

    Mumtaz, R; Ali Khan, A; Noor, N; Humayun, S

    2010-03-01

    To assess amalgam use and waste management protocols practised by Pakistani dentists, a cross-sectional study was made of 239 dentists in Islamabad and Rawalpindi, recruited by convenience and cluster sampling. Amalgam was the most frequently used restorative material, with the choice dictated by patients' financial constraints. While 90.4% of dentists perceived amalgam as a health risk, only 46.4% considered it an environmental hazard. The majority disposed of amalgam waste in the trash, down the sink or as hospital waste. Very few (5.9%) had an amalgam separator installed in their dental office. Amalgam waste management protocols and mercury recycling should be introduced in Pakistan. PMID:20795451

  10. The Great Recession, unemployment and suicide

    PubMed Central

    Norström, Thor; Grönqvist, Hans

    2015-01-01

    Background How have suicide rates responded to the marked increase in unemployment spurred by the Great Recession? Our paper puts this issue into a wider perspective by assessing (1) whether the unemployment-suicide link is modified by the degree of unemployment protection, and (2) whether the effect on suicide of the present crisis differs from the effects of previous economic downturns. Methods We analysed the unemployment-suicide link using time-series data for 30 countries spanning the period 1960–2012. Separate fixed-effects models were estimated for each of five welfare state regimes with different levels of unemployment protection (Eastern, Southern, Anglo-Saxon, Bismarckian and Scandinavian). We included an interaction term to capture the possible excess effect of unemployment during the Great Recession. Results The largest unemployment increases occurred in the welfare state regimes with the least generous unemployment protection. The unemployment effect on male suicides was statistically significant in all welfare regimes, except the Scandinavian one. The effect on female suicides was significant only in the eastern European country group. There was a significant gradient in the effects, being stronger the less generous the unemployment protection. The interaction term capturing the possible excess effect of unemployment during the financial crisis was not significant. Conclusions Our findings suggest that the more generous the unemployment protection the weaker the detrimental impact on suicide of the increasing unemployment during the Great Recession. PMID:25339416

  11. A syndrome of insulin resistance resembling leprechaunism in five sibs of consanguineous parents.

    PubMed Central

    al-Gazali, L I; Khalil, M; Devadas, K

    1993-01-01

    Leprechaunism is a rare autosomal recessive disorder associated with extreme insulin resistance with paradoxical hypo-glycaemia. It is characterised by prenatal and postnatal growth retardation, reduced subcutaneous tissue, coarse features, acanthosis nigricans, enlarged genitalia, and death in the first year of life. Defects in both the insulin receptor and postreceptor steps of the insulin action pathway have been reported. At the molecular level, several mutations have been described. The patients reported here are from a Yemeni family with a syndrome of insulin resistance similar to leprechaunism in which the parents are second cousins and five of their eight children are affected. However, the phenotypes seem to be less severe than the classical leprechaunism previously described. All the children are alive (oldest 11 years), there is normal subcutaneous tissue, and a normal growth pattern in some of them. It may be that this is a milder type of leprechaunism with a better prognosis, perhaps caused by a different type of mutation from those previously described. Images PMID:8326490

  12. 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.

  13. Novel FGF8 Mutations Associated with Recessive Holoprosencephaly, Craniofacial Defects, and Hypothalamo-Pituitary Dysfunction

    PubMed Central

    McCabe, Mark J.; Gaston-Massuet, Carles; Tziaferi, Vaitsa; Gregory, Louise C.; Alatzoglou, Kyriaki S.; Signore, Massimo; Puelles, Eduardo; Gerrelli, Dianne; Farooqi, I. Sadaf; Raza, Jamal; Walker, Joanna; Kavanaugh, Scott I.; Tsai, Pei-San; Pitteloud, Nelly; Martinez-Barbera, Juan-Pedro

    2011-01-01

    Context: Fibroblast growth factor (FGF) 8 is important for GnRH neuronal development with human mutations resulting in Kallmann syndrome. Murine data suggest a role for Fgf8 in hypothalamo-pituitary development; however, its role in the etiology of wider hypothalamo-pituitary dysfunction in humans is unknown. Objective: The objective of this study was to screen for FGF8 mutations in patients with septo-optic dysplasia (n = 374) or holoprosencephaly (HPE)/midline clefts (n = 47). Methods: FGF8 was analyzed by PCR and direct sequencing. Ethnically matched controls were then screened for mutated alleles (n = 480–686). Localization of Fgf8/FGF8 expression was analyzed by in situ hybridization in developing murine and human embryos. Finally, Fgf8 hypomorphic mice (Fgf8loxPNeo/−) were analyzed for the presence of forebrain and hypothalamo-pituitary defects. Results: A homozygous p.R189H mutation was identified in a female patient of consanguineous parentage with semilobar HPE, diabetes insipidus, and TSH and ACTH insufficiency. Second, a heterozygous p.Q216E mutation was identified in a female patient with an absent corpus callosum, hypoplastic optic nerves, and Moebius syndrome. FGF8 was expressed in the ventral diencephalon and anterior commissural plate but not in Rathke's pouch, strongly suggesting early onset hypothalamic and corpus callosal defects in these patients. This was consolidated by significantly reduced vasopressin and oxytocin staining neurons in the hypothalamus of Fgf8 hypomorphic mice compared with controls along with variable hypothalamo-pituitary defects and HPE. Conclusion: We implicate FGF8 in the etiology of recessive HPE and potentially septo-optic dysplasia/Moebius syndrome for the first time to our knowledge. Furthermore, FGF8 is important for the development of the ventral diencephalon, hypothalamus, and pituitary. PMID:21832120

  14. Recessive REEP1 mutation is associated with congenital axonal neuropathy and diaphragmatic palsy

    PubMed Central

    Schottmann, Gudrun; Seelow, Dominik; Seifert, Franziska; Morales-Gonzalez, Susanne; Gill, Esther; von Au, Katja; von Moers, Arpad; Stenzel, Werner

    2015-01-01

    Objective: To identify the underlying genetic cause of a congenital neuropathy in a 5-year-old boy as part of a cohort of 32 patients from 23 families with genetically unresolved neuropathies. Methods: We used autozygosity mapping coupled with next-generation sequencing to investigate a consanguineous family from Lebanon with 1 affected and 2 healthy children. Variants were investigated for segregation in the family by Sanger sequencing. A splice site mutation was further evaluated on the messenger RNA level by quantitative reverse transcription PCR. Subsequently, a larger cohort was specifically screened for receptor expression-enhancing protein 1 (REEP1) gene mutations. Results: We detected a homozygous splice donor mutation in REEP1 (c.303+1-7GTAATAT>AC, p.F62Kfs23*; NM_022912) that cosegregated with the phenotype in the family, leading to complete skipping of exon 4 and a premature stop codon. The phenotype of the patient is similar to spinal muscular atrophy with respiratory distress type 1 (SMARD1) with additional distal arthrogryposis and involvement of the upper motor neuron manifested by pronounced hyperreflexia. Conclusion: To date, only dominant REEP1 mutations have been reported to be associated with a slowly progressive hereditary spastic paraplegia. The findings from our patient expand the phenotypical spectrum and the mode of inheritance of REEP1-associated disorders. Recessive mutations in REEP1 should be considered in the molecular genetic workup of patients with a neuromuscular disorder resembling SMARD1, especially if additional signs of upper motor neuron involvement and distal arthrogryposis are present. PMID:27066569

  15. 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

  16. A Defect in the TUSC3 Gene Is Associated with Autosomal Recessive Mental Retardation

    PubMed Central

    Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas Walter

    2008-01-01

    Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with nonsyndromic ARMR in four sibships. Genome-wide SNP typing enabled us to map the relevant genetic defect to a 4.6 Mbp interval on chromosome 8. Haplotype analyses and copy-number studies led to the identification of a homozygous deletion partly removing TUSC3 (N33) in all patients. All obligate carriers of this family were heterozygous, but none of 192 unrelated healthy individuals from the same population carried this deletion. We excluded other disease-causing mutations in the coding regions of all genes within the linkage interval by sequencing; moreover, we verified the complete absence of a functional TUSC3 transcript in all patients through RT-PCR. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltransferase complex that catalyzes a pivotal step in the protein N-glycosylation process. Our data suggest that in contrast to other genetic defects of glycosylation, inactivation of TUSC3 causes nonsyndromic MR, a conclusion that is supported by a separate report in this issue of AJHG. TUSC3 is only the fifth gene implicated in NS-ARMR and the first for which mutations have been reported in more than one family. PMID:18452889

  17. A defect in the TUSC3 gene is associated with autosomal recessive mental retardation.

    PubMed

    Garshasbi, Masoud; Hadavi, Valeh; Habibi, Haleh; Kahrizi, Kimia; Kariminejad, Roxana; Behjati, Farkhondeh; Tzschach, Andreas; Najmabadi, Hossein; Ropers, Hans Hilger; Kuss, Andreas Walter

    2008-05-01

    Recent studies have shown that autosomal recessive mental retardation (ARMR) is extremely heterogeneous, and there is reason to believe that the number of underlying gene defects goes into the thousands. To date, however, only four genes have been implicated in nonsyndromic ARMR (NS-ARMR): PRSS12 (neurotrypsin), CRBN (cereblon), CC2D1A, and GRIK2. As part of an ongoing systematic study aiming to identify ARMR genes, we investigated a large consanguineous family comprising seven patients with nonsyndromic ARMR in four sibships. Genome-wide SNP typing enabled us to map the relevant genetic defect to a 4.6 Mbp interval on chromosome 8. Haplotype analyses and copy-number studies led to the identification of a homozygous deletion partly removing TUSC3 (N33) in all patients. All obligate carriers of this family were heterozygous, but none of 192 unrelated healthy individuals from the same population carried this deletion. We excluded other disease-causing mutations in the coding regions of all genes within the linkage interval by sequencing; moreover, we verified the complete absence of a functional TUSC3 transcript in all patients through RT-PCR. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltransferase complex that catalyzes a pivotal step in the protein N-glycosylation process. Our data suggest that in contrast to other genetic defects of glycosylation, inactivation of TUSC3 causes nonsyndromic MR, a conclusion that is supported by a separate report in this issue of AJHG. TUSC3 is only the fifth gene implicated in NS-ARMR and the first for which mutations have been reported in more than one family. PMID:18452889

  18. Hurler-Scheie phenotype with parental consanguinity. Report of an additional case supporting the concept of genetic heterogeneity.

    PubMed

    Kaibara, N; Katsuki, I; Hotokebuchi, T; Takagishi, K; Kure, T

    1983-05-01

    The Hurler-Scheie phenotype in a 27-year-old woman of first-cousin parentage is possibly the first reported in the orthopedic literature. The patient exhibited short stature, coarse facies, corneal clouding, multiple stiff joints, normal intelligence, and a long history of bilateral carpal tunnel syndrome, which has not been relieved after operation. The irreversible nerve damage was apparently produced by the marked thickening of the transverse carpal ligament. Surgical findings in this case and data from published reports emphasize the need for early surgical treatment of the associated carpal tunnel syndrome in patients with the Hurler-Scheie phenotype. Parental consanguinity present in this patient is further evidence supporting the concept of a third mutant allele different from both the Hurler gene and the Scheie gene. PMID:6404579

  19. 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

    2016-04-01

    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. PMID:26466513

  20. 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

  1. 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

  2. Classical and Bayesian Seismic Yield Estimation: The 1998 Indian and Pakistani Tests

    NASA Astrophysics Data System (ADS)

    Shumway, R. H.

    2001-10-01

    - The nuclear tests in May, 1998, in India and Pakistan have stimulated a renewed interest in yield estimation, based on limited data from uncalibrated test sites. We study here the problem of estimating yields using classical and Bayesian methods developed by Shumway (1992), utilizing calibration data from the Semipalatinsk test site and measured magnitudes for the 1998 Indian and Pakistani tests given by Murphy (1998). Calibration is done using multivariate classical or Bayesian linear regression, depending on the availability of measured magnitude-yield data and prior information. Confidence intervals for the classical approach are derived applying an extension of Fieller's method suggested by Brown (1982). In the case where prior information is available, the posterior predictive magnitude densities are inverted to give posterior intervals for yield. Intervals obtained using the joint distribution of magnitudes are comparable to the single-magnitude estimates produced by Murphy (1998) and reinforce the conclusion that the announced yields of the Indian and Pakistani tests were too high.

  3. Classical and Bayesian Seismic Yield Estimation: The 1998 Indian and Pakistani Tests

    NASA Astrophysics Data System (ADS)

    Shumway, R. H.

    The nuclear tests in May, 1998, in India and Pakistan have stimulated a renewed interest in yield estimation, based on limited data from uncalibrated test sites. We study here the problem of estimating yields using classical and Bayesian methods developed by Shumway (1992), utilizing calibration data from the Semipalatinsk test site and measured magnitudes for the 1998 Indian and Pakistani tests given by Murphy (1998). Calibration is done using multivariate classical or Bayesian linear regression, depending on the availability of measured magnitude-yield data and prior information. Confidence intervals for the classical approach are derived applying an extension of Fieller's method suggested by Brown (1982). In the case where prior information is available, the posterior predictive magnitude densities are inverted to give posterior intervals for yield. Intervals obtained using the joint distribution of magnitudes are comparable to the single-magnitude estimates produced by Murphy (1998) and reinforce the conclusion that the announced yields of the Indian and Pakistani tests were too high.

  4. 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

  5. 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...

  6. 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…

  7. 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…

  8. "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…

  9. 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

  10. 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

  11. 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

  12. Fuel compositions for lessening valve seat recession

    SciTech Connect

    Johnston, T.E.; Dorer, C.J. Jr.

    1987-04-21

    A fuel composition is described for internal combustion engines comprising a major amount of a liquid hydrocarbon fuel and a minor, property improving amount sufficient to reduce valve seat recession when the fuel is used in an internal combustion engine of (A) at least one hydrocarbon-soluble alkali or alkaline earth metal containing composition containing at least 8 aliphatic carbon atoms and (B) at least one hydrocarbon-soluble ashless dispersant wherein (A) is the alkali metal or alkaline earth metal salt of a sulfur acid, a carboxylic acid or a phenol.

  13. 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

  14. 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

  15. 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. PMID:26246154

  16. Identification of a Novel MYO15A Mutation in a Chinese Family with Autosomal Recessive Nonsyndromic Hearing Loss

    PubMed Central

    Xia, Hong; Huang, Xiangjun; Guo, Yi; Hu, Pengzhi; He, Guangxiang; Deng, Xiong; Xu, Hongbo; Yang, Zhijian; Deng, Hao

    2015-01-01

    Autosomal recessive nonsyndromic hearing loss (ARNSHL) is a genetically heterogeneous sensorineural disorder, generally manifested with prelingual hearing loss and absence of other clinical manifestations. The aim of this study is to identify the pathogenic gene in a four-generation consanguineous Chinese family with ARNSHL. A novel homozygous variant, c.9316dupC (p.H3106Pfs*2), in the myoxin XVa gene (MYO15A) was identified by exome sequencing and Sanger sequencing. The homozygous MYO15A c.9316dupC variant co-segregated with the phenotypes in the ARNSHL family and was absent in two hundred normal controls. The variant was predicted to interfere with the formation of the Myosin XVa-whirlin-Eps8 complex at the tip of stereocilia, which is indispensable for stereocilia elongation. Our data suggest that the homozygous MYO15A c.9316dupC variant might be the pathogenic mutation, and exome sequencing is a powerful molecular diagnostic strategy for ARNSHL, an extremely heterogeneous disorder. Our findings extend the mutation spectrum of the MYO15A gene and have important implications for genetic counseling for the family. PMID:26308726

  17. 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. PMID:26206890

  18. A mutation of COX6A1 causes a recessive axonal or mixed form of Charcot-Marie-Tooth disease.

    PubMed

    Tamiya, Gen; Makino, Satoshi; Hayashi, Makiko; Abe, Akiko; Numakura, Chikahiko; Ueki, Masao; Tanaka, Atsushi; Ito, Chizuru; Toshimori, Kiyotaka; Ogawa, Nobuhiro; Terashima, Tomoya; Maegawa, Hiroshi; Yanagisawa, Daijiro; Tooyama, Ikuo; Tada, Masayoshi; Onodera, Osamu; Hayasaka, Kiyoshi

    2014-09-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247-10_247-6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT. PMID:25152455

  19. A Mutation of COX6A1 Causes a Recessive Axonal or Mixed Form of Charcot-Marie-Tooth Disease

    PubMed Central

    Tamiya, Gen; Makino, Satoshi; Hayashi, Makiko; Abe, Akiko; Numakura, Chikahiko; Ueki, Masao; Tanaka, Atsushi; Ito, Chizuru; Toshimori, Kiyotaka; Ogawa, Nobuhiro; Terashima, Tomoya; Maegawa, Hiroshi; Yanagisawa, Daijiro; Tooyama, Ikuo; Tada, Masayoshi; Onodera, Osamu; Hayasaka, Kiyoshi

    2014-01-01

    Charcot-Marie-Tooth disease (CMT) is the most common inherited neuropathy characterized by clinical and genetic heterogeneity. Although more than 30 loci harboring CMT-causing mutations have been identified, many other genes still remain to be discovered for many affected individuals. For two consanguineous families with CMT (axonal and mixed phenotypes), a parametric linkage analysis using genome-wide SNP chip identified a 4.3 Mb region on 12q24 showing a maximum multipoint LOD score of 4.23. Subsequent whole-genome sequencing study in one of the probands, followed by mutation screening in the two families, revealed a disease-specific 5 bp deletion (c.247−10_247−6delCACTC) in a splicing element (pyrimidine tract) of intron 2 adjacent to the third exon of cytochrome c oxidase subunit VIa polypeptide 1 (COX6A1), which is a component of mitochondrial respiratory complex IV (cytochrome c oxidase [COX]), within the autozygous linkage region. Functional analysis showed that expression of COX6A1 in peripheral white blood cells from the affected individuals and COX activity in their EB-virus-transformed lymphoblastoid cell lines were significantly reduced. In addition, Cox6a1-null mice showed significantly reduced COX activity and neurogenic muscular atrophy leading to a difficulty in walking. Those data indicated that COX6A1 mutation causes the autosomal-recessive axonal or mixed CMT. PMID:25152455

  20. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia.

    PubMed

    Adaimy, Lynn; Chouery, Eliane; Megarbane, Hala; Mroueh, Salman; Delague, Valerie; Nicolas, Elsa; Belguith, Hanen; de Mazancourt, Philippe; Megarbane, Andre

    2007-10-01

    Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ~9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G-->T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases. PMID:17847007

  1. Mutation in WNT10A Is Associated with an Autosomal Recessive Ectodermal Dysplasia: The Odonto-onycho-dermal Dysplasia

    PubMed Central

    Adaimy, Lynn ; Chouery, Eliane ; Mégarbané, Hala ; Mroueh, Salman ; Delague, Valérie ; Nicolas, Elsa ; Belguith, Hanen ; de Mazancourt, Philippe ; Mégarbané, André 

    2007-01-01

    Odonto-onycho-dermal dysplasia is a rare autosomal recessive syndrome in which the presenting phenotype is dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. We studied three consanguineous Lebanese Muslim Shiite families that included six individuals affected with odonto-onycho-dermal dysplasia. Using a homozygosity-mapping strategy, we assigned the disease locus to an ∼9-cM region at chromosome 2q35-q36.2, located between markers rs16853834 and D2S353, with a maximum multipoint LOD score of 5.7. Screening of candidate genes in this region led us to identify the same c.697G→T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in all patients. At the protein level, the mutation is predicted to result in a premature truncated protein of 232 aa instead of 417 aa. This is the first report to our knowledge of a human phenotype resulting from a mutation in WNT10A, and it is the first demonstration of an ectodermal dysplasia caused by an altered WNT signaling pathway, expanding the list of WNT-related diseases. PMID:17847007

  2. Mutations in PTPRQ are a cause of autosomal-recessive nonsyndromic hearing impairment DFNB84 and associated with vestibular dysfunction.

    PubMed

    Schraders, Margit; Oostrik, Jaap; Huygen, Patrick L M; Strom, Tim M; van Wijk, Erwin; Kunst, Henricus P M; Hoefsloot, Lies H; Cremers, Cor W R J; Admiraal, Ronald J C; Kremer, Hannie

    2010-04-01

    We identified overlapping homozygous regions within the DFNB84 locus in a nonconsanguineous Dutch family and a consanguineous Moroccan family with sensorineural autosomal-recessive nonsyndromic hearing impairment (arNSHI). The critical region of 3.17 Mb harbored the PTPRQ gene and mouse models with homozygous mutations in the orthologous gene display severe hearing loss. We show that the human PTPRQ gene was not completely annotated and that additional, alternatively spliced exons are present at the 5' end of the gene. Different PTPRQ isoforms are encoded with a varying number of fibronectin type 3 (FN3) domains, a transmembrane domain, and a phosphatase domain. Sequence analysis of the PTPRQ gene in members of the families revealed a nonsense mutation in the Dutch family and a missense mutation in the Moroccan family. The missense mutation is located in one of the FN3 domains. The nonsense mutation results in a truncated protein with only a small number of FN3 domains and no transmembrane or phosphatase domain. Hearing loss in the patients with PTPRQ mutations is likely to be congenital and moderate to profound and most severe in the family with the nonsense mutation. Progression of the hearing loss was observed in both families. The hearing loss is accompanied by vestibular dysfunction in all affected individuals. Although we show that PTPRQ is expressed in many tissues, no symptoms other than deafness were observed in the patients. PMID:20346435

  3. Megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), an autosomal recessive disorder: clinical reports and review of the literature.

    PubMed

    Annerén, G; Meurling, S; Olsen, L

    1991-11-01

    We present 2 new patients with the megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS), review the literature, and discuss the prenatal diagnosis and treatment. MMIHS, as reported in 43 cases, is usually lethal. Most children die during the first year of life, and only 3 children survived their first year. We report the 6th pair of sibs with the disease. Overall, 17 patients reported have had sibs with MMIHS or the parents were consanguineous; 4 times the parents were first, cousins, confirming that this is an autosomal recessive disorder. The present 2 children, whose parents also were first cousins, were of different sex. They had typical MMIHS with abdominal distension due to pronounced megacystis, hydronephrosis, microcolon, and microileum, involving the distal part of the ileum, malrotation of the gut, and intestinal hypoperistalsis. Neither surgery nor medical treatment was successful and the children died at the age of 19 days and 2 1/2 months, respectively. There is no cure for the disease. However, a new protkinetic drug, Cisapride might be worth trying in these cases. Prenatal ultrasound diagnosis of MMIHS might be possible. PMID:1785644

  4. The role of the olfactory recess in olfactory airflow.

    PubMed

    Eiting, Thomas P; Smith, Timothy D; Perot, J Blair; Dumont, Elizabeth R

    2014-05-15

    The olfactory recess - a blind pocket at the back of the nasal airway - is thought to play an important role in mammalian olfaction by sequestering air outside of the main airstream, thus giving odorants time to re-circulate. Several studies have shown that species with large olfactory recesses tend to have a well-developed sense of smell. However, no study has investigated how the size of the olfactory recess relates to air circulation near the olfactory epithelium. Here we used a computer model of the nasal cavity from a bat (Carollia perspicillata) to test the hypothesis that a larger olfactory recess improves olfactory airflow. We predicted that during inhalation, models with an enlarged olfactory recess would have slower rates of flow through the olfactory region (i.e. the olfactory recess plus airspace around the olfactory epithelium), while during exhalation these models would have little to no flow through the olfactory recess. To test these predictions, we experimentally modified the size of the olfactory recess while holding the rest of the morphology constant. During inhalation, we found that an enlarged olfactory recess resulted in lower rates of flow in the olfactory region. Upon exhalation, air flowed through the olfactory recess at a lower rate in the model with an enlarged olfactory recess. Taken together, these results indicate that an enlarged olfactory recess improves olfactory airflow during both inhalation and exhalation. These findings add to our growing understanding of how the morphology of the nasal cavity may relate to function in this understudied region of the skull. PMID:24577441

  5. Autosomal recessive nonsyndromic deafness genes: a review

    PubMed Central

    Duman, Duygu; Tekin, Mustafa

    2013-01-01

    More than 50 percent of prelingual hearing loss is genetic in origin, and of these up to 93 percent are monogenic autosomal recessive traits. Some forms of genetic deafness can be recognized by their associated syndromic features, but in most cases, hearing loss is the only finding and is referred to as nonsyndromic deafness. To date, more than 700 different mutations have been identified in one of 42 genes in individuals with autosomal recessive nonsyndromic hearing loss (ARNSHL). Reported mutations in GJB2, encoding connexin 26, makes this gene the most common cause of hearing loss in many populations. Other relatively common deafness genes include SLC26A4, MYO15A, OTOF, TMC1, CDH23, and TMPRSS3. In this report we summarize genes and mutations reported in families with ARNSHL. Founder effects were demonstrated for some recurrent mutations but the most significant findings are the extreme locus and allelic heterogeneity and different spectrum of genes and mutations in each population. PMID:22652773

  6. 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

  7. Hereditary Sensory Autonomic Neuropathy II, a rare disease in a large Pakistani family.

    PubMed

    Arain, Fazal Manzoor; Chand, Prem

    2015-10-01

    Hereditary Sensory Autonomic Neuropathy II (HSAN II) is a rare genetic disorder, characterized by severe loss of pain, temperature and touch sensation. Injuries in these patients can progress to necrosis and shedding of digits and limbs. Here we report two cases of HSAN II belonging to a Pakistani family. Individual 1, a forty five year old man, had complete loss of pain sensation since birth. Self-mutilation and complication of injuries resulted in the shedding of all the digits and right foot and surgical amputation of left leg. Individual 2, a five year old girl,had delay in healing of wounds and self-mutilation. Examination showed a complete lack of pain sensation throughout her body and hyporeflexia. As the genetic cause of HSAN II is unknown, identification of more patients will allow further research on this disease and possibly develop a cure. PMID:26440849

  8. Identification of three rare beta-thalassemia mutations in the Pakistani population.

    PubMed

    Khan, S N; Riazuddin, S; Galanello, R

    2000-02-01

    Three rare beta-thalassemia mutations, not reported previously in Asian Indians or the Pakistani population, were identified by single strand conformation polymorphism analysis followed by direct sequencing. Two mutations, IVS-II-848 (C-->A) and initiation codon (ATG-->ACG), were found in the homozygous condition in patients belonging to Balochi and Sindhi ethnic groups of Pakistan, together with heterozygous and homozygous alpha(-3.7) deletions, respectively. A frameshift mutation at codon 44 (-C) was identified in a patient belonging to the Gujrati ethnic group together with IVS-I-1 (G-->T) and a normal complement of four a-globin genes. Haplotype analysis was performed to identify the chromosomal background associated with these mutations, and for tracing the origin and spread of these mutations. PMID:10722111

  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. PMID:11982043

  10. 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. PMID:25130573

  11. Association between maternal age and pregnancy outcome: implications for the Pakistani society.

    PubMed

    Hanif, Hafsa Muhammad

    2011-03-01

    Maternal age at conception has long been demonstrated to have a significant correlation with pregnancy outcome and maternal health. Classically, very young (<20 years old) and old (= or >35 years) women have been classified as high-risk categories for child bearing. Recently, career, education, financial, and other goals have coerced women to delay childbearing all over the world. This trend is also becoming apparent in Pakistan, especially in the upper middle class, wealthy and educated women, as they become increasingly empowered. This review presents the association between maternal age and pregnancy outcome, particularly in the context of statistics of Pakistan, and its possible repercussions. On one hand, physicians need to develop effective counseling strategies for their patients in this regard, and on the other, more studies are required to ascertain the attitudes of Pakistani women, particularly those belonging to the upper and middle classes, regarding delayed childbearing, that can aid physicians in formulating effective counseling strategies. PMID:21465960

  12. Comparison of structural architecture of HCV NS3 genotype 1 versus Pakistani genotype 3a.

    PubMed

    Fatima, Kaneez; Azhar, Esam; Mathew, Shilu; Damanhouri, Ghazi; Qadri, Ishtiaq

    2014-01-01

    This study described the structural characterization of Pakistani HCV NS3 GT3a in parallel with genotypes 1a and 1b NS3. We investigated the role of amino acids and their interaction patterns in different HCV genotypes by crystallographic modeling. Different softwares were used to study the interaction pattern, for example, CLCBIO sequence viewer, MODELLER, NMRCLUST, ERRAT score, and MODELLER. Sixty models were produced and clustered into groups and the best model of PK-NCVI/Pk3a NS3 was selected and studied further to check the variability with other HCV NS3 genotypes. This study will help in future to understand the structural architecture of HCV genome variability and to further define the conserved targets for antiviral agents. PMID:25401105

  13. Comparison of Structural Architecture of HCV NS3 Genotype 1 versus Pakistani Genotype 3a

    PubMed Central

    Mathew, Shilu; Damanhouri, Ghazi

    2014-01-01

    This study described the structural characterization of Pakistani HCV NS3 GT3a in parallel with genotypes 1a and 1b NS3. We investigated the role of amino acids and their interaction patterns in different HCV genotypes by crystallographic modeling. Different softwares were used to study the interaction pattern, for example, CLCBIO sequence viewer, MODELLER, NMRCLUST, ERRAT score, and MODELLER. Sixty models were produced and clustered into groups and the best model of PK-NCVI/Pk3a NS3 was selected and studied further to check the variability with other HCV NS3 genotypes. This study will help in future to understand the structural architecture of HCV genome variability and to further define the conserved targets for antiviral agents. PMID:25401105

  14. Targeted Next-Generation Sequencing of a 12.5 Mb Homozygous Region Reveals ANO10 Mutations in Patients with Autosomal-Recessive Cerebellar Ataxia

    PubMed Central

    Vermeer, Sascha; Hoischen, Alexander; Meijer, Rowdy P.P.; Gilissen, Christian; Neveling, Kornelia; Wieskamp, Nienke; de Brouwer, Arjan; Koenig, Michel; Anheim, Mathieu; Assoum, Mirna; Drouot, Nathalie; Todorovic, Slobodanka; Milic-Rasic, Vedrana; Lochmüller, Hanns; Stevanin, Giovanni; Goizet, Cyril; David, Albert; Durr, Alexandra; Brice, Alexis; Kremer, Berry; van de Warrenburg, Bart P.C.; Schijvenaars, Mascha M.V.A.P.; Heister, Angelien; Kwint, Michael; Arts, Peer; van der Wijst, Jenny; Veltman, Joris; Kamsteeg, Erik-Jan; Scheffer, Hans; Knoers, Nine

    2010-01-01

    Autosomal-recessive cerebellar ataxias comprise a clinically and genetically heterogeneous group of neurodegenerative disorders. In contrast to their dominant counterparts, unraveling the molecular background of these ataxias has proven to be more complicated and the currently known mutations provide incomplete coverage for genotyping of patients. By combining SNP array-based linkage analysis and targeted resequencing of relevant sequences in the linkage interval with the use of next-generation sequencing technology, we identified a mutation in a gene and have shown its association with autosomal-recessive cerebellar ataxia. In a Dutch consanguineous family with three affected siblings a homozygous 12.5 Mb region on chromosome 3 was targeted by array-based sequence capture. Prioritization of all detected sequence variants led to four candidate genes, one of which contained a variant with a high base pair conservation score (phyloP score: 5.26). This variant was a leucine-to-arginine substitution in the DUF 590 domain of a 16K transmembrane protein, a putative calcium-activated chloride channel encoded by anoctamin 10 (ANO10). The analysis of ANO10 by Sanger sequencing revealed three additional mutations: a homozygous mutation (c.1150_1151del [p.Leu384fs]) in a Serbian family and a compound-heterozygous splice-site mutation (c.1476+1G>T) and a frameshift mutation (c.1604del [p.Leu535X]) in a French family. This illustrates the power of using initial homozygosity mapping with next-generation sequencing technology to identify genes involved in autosomal-recessive diseases. Moreover, identifying a putative calcium-dependent chloride channel involved in cerebellar ataxia adds another pathway to the list of pathophysiological mechanisms that may cause cerebellar ataxia. PMID:21092923

  15. 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

  16. Radiological impact of dietary intakes of naturally occurring radionuclides on Pakistani adults.

    PubMed

    Akhter, P; Rahman, K; Orfi, S D; Ahmad, N

    2007-02-01

    Daily dietary intakes of three naturally occurring long-lived radionuclides (232)Th, (238)U and (40)K were estimated for the adult population of Pakistan using neutron activation analysis (NAA), inductively coupled plasma mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS), respectively. The daily intakes of (232)Th ranged from 4 to 29 mBq, (238)U ranged from 17 to 82 mBq and (40)K ranged from 51 to 128 Bq. The geometric means of these intakes were 10 mBqd(-1) for (232)Th, 33 mBqd(-1) for (238)U and 78.5 Bqd(-1) for (40)K. The measured values give annual committed effective doses of 0.80, 0.53 and 178.75 microSvyr(-1) for (232)Th, (238)U and (40)K, respectively to Pakistani population. The net radiological impact of these radionuclides is 180.08 microSvyr(-1). This value gives cancer risk factor of 4.5 x 10(-4) and loss of life expectancy of 0.87 days only. Whereas ICRP cancer risk factor for general public is 2.5 x 10(-3) and total risk involve from the all natural radiation sources based on global average annual radiation dose of 2.4 mSvyr(-1) is 6.0 x 10(-3). The estimated cancer risk shows that probability of increase of cancer risk from daily Pakistani diet is only a minor fraction of ICRP values. Therefore, the diet does not pose any significant health hazard and is considered radiologically safe for human consumption. PMID:17034921

  17. 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

  18. 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

  19. 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

  20. 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. PMID:25651572

  1. 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

  2. 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…

  3. Women and Jobs in Recessions: 1969-92.

    ERIC Educational Resources Information Center

    Goodman, William; And Others

    1993-01-01

    The probability of losing one's job because of a recession is very different for women and men, but, in the last two recessions, gender differences were reduced. The major cause is the relative performance of industries that heavily employ women (such as services) versus those that heavily employ men (such as goods-producing). (JOW)

  4. Recess Physical Activity Packs in Elementary Schools: A Qualitative Investigation

    ERIC Educational Resources Information Center

    Elliott, Steven; Combs, Sue; Boyce, Robert

    2011-01-01

    To supplement the present weekly allotment of 30 minutes of physical education, a school district in southeastern North Carolina identified recess time as part of the state mandated (HSP-S-000) 150 minutes of physical activity (PA) per week and have purchased fitness equipment (recess packs) for the children to use. Twelve participants were…

  5. 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…

  6. 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…

  7. 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…

  8. 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…

  9. 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…

  10. 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…

  11. Homozygosity mapping and targeted genomic sequencing reveal the gene responsible for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred

    PubMed Central

    Gulsuner, Suleyman; Tekinay, Ayse Begum; Doerschner, Katja; Boyaci, Huseyin; Bilguvar, Kaya; Unal, Hilal; Ors, Aslihan; Onat, O. Emre; Atalar, Ergin; Basak, A. Nazli; Topaloglu, Haluk; Kansu, Tulay; Tan, Meliha; Tan, Uner; Gunel, Murat; Ozcelik, Tayfun

    2011-01-01

    The biological basis for the development of the cerebro-cerebellar structures required for posture and gait in humans is poorly understood. We investigated a large consanguineous family from Turkey exhibiting an extremely rare phenotype associated with quadrupedal locomotion, mental retardation, and cerebro-cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome 17p13.1–13.3. Diffusion weighted imaging and fiber tractography of the patients' brains revealed morphological abnormalities in the cerebellum and corpus callosum, in particular atrophy of superior, middle, and inferior peduncles of the cerebellum. Structural magnetic resonance imaging showed additional morphometric abnormalities in several cortical areas, including the corpus callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted sequencing of the entire homozygous region in three affected individuals and two obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which cosegregated with the condition in the extended family. The mutation lies in a highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C-terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane protein. It is highly expressed in the cerebellum and corpus callosum, in particular in the Purkinje cell layer of the cerebellum. WDR81 represents the third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans. PMID:21885617

  12. Exome sequencing identified a novel de novo OPA1 mutation in a consanguineous family presenting with optic atrophy.

    PubMed

    Cohen, Lior; Tzur, Shay; Goldenberg-Cohen, Nitza; Bormans, Concetta; Behar, Doron M; Reinstein, Eyal

    2016-01-01

    Inherited optic neuropathies are a heterogeneous group of disorders characterized by mild to severe visual loss, colour vision deficit, central or paracentral visual field defects and optic disc pallor. Optic atrophies can be classified into isolated or non-syndromic and syndromic forms. While multiple modes of inheritance have been reported, autosomal dominant optic atrophy and mitochondrial inherited Leber's hereditary optic neuropathy are the most common forms. Optic atrophy type 1, caused by mutations in the OPA1 gene is believed to be the most common hereditary optic neuropathy, and most patients inherit a mutation from an affected parent. In this study we used whole-exome sequencing to investigate the genetic aetiology in a patient affected with isolated optic atrophy. Since the proband was the only affected individual in his extended family, and was a product of consanguineous marriage, homozygosity mapping followed by whole-exome sequencing were pursued. Exome results identified a novel de novo OPA1 mutation in the proband. We conclude, that though de novo OPA1 mutations are uncommon, testing of common optic atrophy-associated genes such as mitochondrial mutations and OPA1 gene sequencing should be performed first in single individuals presenting with optic neuropathy, even when dominant inheritance is not apparent. PMID:27265430

  13. New mutations in BBS genes in small consanguineous families with Bardet-Biedl syndrome: Detection of candidate regions by homozygosity mapping

    PubMed Central

    Pereiro, Ines; Piñeiro-Gallego, Teresa; Baiget, Montserrat; Borrego, Salud; Ayuso, Carmen; Searby, Charles; Nishimura, Darryl

    2010-01-01

    Purpose Bardet-Biedl syndrome (BBS, OMIM 209900) is a rare multi-organ disorder in which BBS patients manifest a variable phenotype that includes retinal dystrophy, polydactyly, mental delay, obesity, and also reproductive tract and renal abnormalities. Mutations in 14 genes (BBS1–BBS14) are found in 70% of the patients, indicating that additional mutations in known and new BBS genes remain to be identified. Therefore, the molecular diagnosis of this complex disorder is a challenging task. Methods In this study we show the use of the genome-wide homozygosity mapping strategy in the mutation detection of nine Caucasian BBS families, eight of them consanguineous and one from the same geographic area with no proven consanguinity. Results We identified the disease-causing mutation in six of the families studied, five of which had novel sequence variants in BBS3, BBS6, and BBS12. This is the first null mutation reported in BBS3. Furthermore, this approach defined homozygous candidate regions that could harbor potential candidate genes for BBS in three of the families. Conclusions These findings further underline the importance of homozygosity mapping as a useful technology for diagnosis in small consanguineous families with a complex disease like BBS. PMID:20142850

  14. A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage

    PubMed Central

    Zhu, Ye; Gu, Xiang; Xu, Chao

    2016-01-01

    Background: Cardiovascular diseases, including dilated cardiomyopathy (DCM) and hypertension, are the leading cause of death worldwide. The role of mitochondrial DNA (mtDNA) in the pathogenesis of these diseases has not been completely clarified. In this study, we evaluate whether A8701G mutation is associated with maternally inherited hypertension and DCM in a Chinese pedigree of a consanguineous marriage. Methods: Fourteen subjects in a three-generation Han Chinese family with hypertension and DCM, in which consanguineous marriage was present in the parental generation, were interviewed. We divided all the family members into case (7 maternal members) and control group (7 nonmaternal members) for comparison. Clinical evaluations and sequence analysis of mtDNA were obtained from all participants. Frequency differences between maternal and nonmaternal members were tested to locate the disease-associated mutations. Results: The majority of the family members presented with a maternal inheritance of hypertension and DCM. Sequence analysis of mtDNA in this pedigree identified eight mtDNA mutations. Among the mutations identified, there was only one significant mutation: A8701G (P = 0.005), which is a homoplasmic mitochondrial missense mutation in all the matrilineal relatives. There was no clear evidence for any synergistic effects between A8701G and other mutations. Conclusions: A8701G mutation may act as an inherited risk factor for the matrilineal transmission of hypertension and DCM in conjunction with genetic disorders caused by consanguineous marriage. PMID:26831225

  15. Phylogenetic and 2D/3D Analysis of HCV 1a NS4A Gene/Protein in Pakistani Isolates

    PubMed Central

    Hussain, Abrar; Idrees, Muhammad; Asif, Muhammad; Ali, Liaqat; Rasool, Mahmood

    2015-01-01

    Background: The nonstructural protein NS4A of hepatitis C virus is composed of 54 amino acids. This small size protein has vital role in many cellular functions. The most important reported function is being a cofactor of viral enzymes serine protease and helicase. Objectives: The objective of this study was to analyze the phylogenetic variation, its impact in terms of translation and any functional change in protein structure at primary 2D/3D structure using computational tools from Pakistani patients isolates. Materials and Methods: Patient sera infected with Hepatitis C virus, genotype 1A, were obtained from Molecular Diagnostics lab, CEMB, University of the Punjab Lahore by using BD Vacutainer collection tubes (Becton Dickenson). Results: Phylogenetic analysis of the gene revealed that Pakistani 1a HCV strains are in the start of third cluster and there is a difference between inter Pakistani isolates at primary, secondary and tertiary levels. Conclusions: Mutations were present in the central domain of NS4A (amino acids 21 - 34). PMID:26288631

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Periodontal regeneration in gingival recession defects.

    PubMed

    Trombelli, L

    1999-02-01

    Surgical treatment of gingival recession defects aims at obtaining soft tissue coverage of exposed root surfaces and/or augmentation of gingival tissue dimensions. A variety of protocols have been developed to manage these clinical problems. Since one goal of periodontal therapy is the regeneration of the lost attachment apparatus of the tooth, full restoration of defect should be accomplished following mucogingival procedures. This implies regeneration of all periodontal structures, including formation of new cementum with inserting connective tissue fibers, alveolar bone regeneration and recreation of a functional and aesthetic morphology of the mucogingival complex. Animal and human histological studies have shown that healing at gingiva-root interface following pedicle flaps or free soft tissue grafts generally includes a long junctional epithelium with varying amounts of a new connective tissue attachment in the most apical aspect of the covered root surface. Limited bone regeneration has been observed. Adjunctive use of root conditioning agents and cell excluding, wound-stabilizing devices may amplify regenerative outcomes. Changes in the amount of keratinized tissue, which can significantly affect the aesthetic outcome of treatment, have been shown to depend on the interactions among various tissues involved in the healing process and the selected surgical procedure. PMID:10321221

  2. Economic recession and mental health: an overview.

    PubMed

    Cooper, Brian

    2011-01-01

    Effects of the current global economic downturn on population mental health will emerge in the years ahead. Judging from earlier experience of financial crises in various parts of the world, stresses associated with rising unemployment, poverty and social insecurity will lead to upward trends in many national suicide rates, as well as to less readily charted increase in the prevalence of psychiatric illness, alcohol-related disorders and illicit drug use. At the same time, mental health services are being cut back as part of government austerity programs. Budget cuts will thus affect psychiatric services adversely just when economic stressors are raising the levels of need and demand in affected populations. Proactive fiscal and social policies could, however, help to mitigate the health consequences of recession. Evidence- based preventive measures include active labor market and family support programs, regulation of alcohol prices and availability, community care for known high-risk groups, and debt relief projects. Economic mental health care could best be achieved, not by decimating services but by planning and deploying these to meet the needs of defined area populations. PMID:21968374

  3. Laminar flow in a recess of a hydrostatic bearing

    NASA Technical Reports Server (NTRS)

    San Andres, Luis A.; Velthuis, Johannes F. M.

    1992-01-01

    The flow in a recess of a hydrostatic journal bearing is studied in detail. The Navier-Stokes equations for the laminar flow of an incompressible liquid are solved numerically in a two-dimensional plane of a typical bearing recess. Pressure- and shear-induced flows, as well as a combination of these two flow conditions, are analyzed. Recess friction, pressure-ram effects at discontinuities in the flow region, and film entrance pressure loss effects are calculated. Entrance pressure loss coefficients over a forward-facing step are presented as functions of the mean flow Reynolds number for pure-pressure and shear-induced laminar flows.

  4. The nonuniform recession of the south polar cap of Mars

    NASA Technical Reports Server (NTRS)

    Veverka, J.; Goguen, J.

    1973-01-01

    The nature of the irregular springtime recession of the Martian polar caps is investigated, with particular reference to the southern polar cap. Our current knowledge about the composition of the caps is outlined, and the historical record of their springtime recession is reviewed. An attempt is made to correlate the irregularities of the recession pattern of the southern polar cap with the features of the terrain revealed by Mariner 9 photography at a time when the southern cap was at its minimum extent. The results are interpreted in terms of the physical and meteorological processes active in the polar regions.

  5. 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

  6. Polymorphisms in MTHFR, MS and CBS Genes and Homocysteine Levels in a Pakistani Population

    PubMed Central

    Yakub, Mohsin; Moti, Naushad; Parveen, Siddiqa; Chaudhry, Bushra; Azam, Iqbal; Iqbal, Mohammad Perwaiz

    2012-01-01

    Background Hyperhomocysteinemia (>15 µmol/L) is highly prevalent in South Asian populations including Pakistan. In order to investigate the genetic determinants of this condition, we studied 6 polymorphisms in genes of 3 enzymes - methylenetetrahydrofolate reductase (MTHFR; C677T; A1298C), methionine synthase (MS; A2756G), cystathionine-β-synthase (CBS; T833C/844ins68, G919A) involved in homocysteine metabolism and investigated their interactions with nutritional and environmental factors in a Pakistani population. Methodology/Principal Findings In a cross-sectional survey, 872 healthy adults (355 males and 517 females; age 18–60 years) were recruited from a low-income urban population in Karachi. Fasting venous blood was obtained and assessed for plasma/serum homocysteine; folate, vitamin B12, pyridoxal phosphate and blood lead. DNA was isolated and genotyping was performed by PCR-RFLP (restriction-fragment-length- polymorphism) based assays. The average changes in homocysteine levels for MTHFR 677CT and TT genotypes were positive [β(SE β), 2.01(0.63) and 16.19(1.8) µmol/L, respectively]. Contrary to MTHFR C677T polymorphism, the average changes in plasma homocysteine levels for MS 2756AG and GG variants were negative [β(SE β), −0.56(0.58) and −0.83(0.99) µmol/L, respectively]. The average change occurring for CBS 844ins68 heterozygous genotype (ancestral/insertion) was −1.88(0.81) µmol/L. The combined effect of MTHFR C677T, MS A2756G and CBS 844ins68 genotypes for plasma homocysteine levels was additive (p value <0.001). Odds of having hyperhomocysteinemia with MTHFR 677TT genotype was 10-fold compared to MTHFR 677CC genotype [OR (95%CI); 10.17(3.6–28.67)]. Protective effect towards hyperhomocysteinemia was observed with heterozygous (ancestral/insertion) genotype of CBS 844ins68 compared to homozygous ancestral type [OR (95% CI); 0.58 (0.34–0.99)]. Individuals with MTHFR 677CT or TT genotypes were at a greater risk of hyperhomocysteinemia in

  7. A Case of Nasu-Hakola Disease without Fractures or Consanguinity Diagnosed Using Exome Sequencing and Treated with Sodium Valproate

    PubMed Central

    Yamazaki, Kiyohiro; Yoshino, Yuta; Mori, Yoko; Ochi, Shinichiro; Yoshida, Taku; Ishimaru, Takashi; Ueno, Shu-ichi

    2015-01-01

    Nasu-Hakola disease (NHD) is a rare autosomal recessive neuropsychiatric disorder characterized by bone cysts, fractures, and cognitive impairment. Two genes are responsible for the development of NHD; TYROBP and TREM2. Although it presents with typical signs and symptoms, diagnosing this disease remains difficult. This case report describes a male with NHD with no family or past history of bone fractures who was diagnosed using exome sequencing. His frontal lobe psychiatric symptoms recovered partially following treatment with sodium valproate, but not with an antipsychotic. PMID:26598595

  8. Whole-Exome Sequencing Efficiently Detects Rare Mutations in Autosomal Recessive Nonsyndromic Hearing Loss

    PubMed Central

    Diaz-Horta, Oscar; Duman, Duygu; Foster, Joseph; Sırmacı, Aslı; Gonzalez, Michael; Mahdieh, Nejat; Fotouhi, Nikou; Bonyadi, Mortaza; Cengiz, Filiz Başak; Menendez, Ibis; Ulloa, Rick H.; Edwards, Yvonne J. K.; Züchner, Stephan; Blanton, Susan; Tekin, Mustafa

    2012-01-01

    Identification of the pathogenic mutations underlying autosomal recessive nonsyndromic hearing loss (ARNSHL) is difficult, since causative mutations in 39 different genes have so far been reported. After excluding mutations in the most common ARNSHL gene, GJB2, via Sanger sequencing, we performed whole-exome sequencing (WES) in 30 individuals from 20 unrelated multiplex consanguineous families with ARNSHL. Agilent SureSelect Human All Exon 50 Mb kits and an Illumina Hiseq2000 instrument were used. An average of 93%, 84% and 73% of bases were covered to 1X, 10X and 20X within the ARNSHL-related coding RefSeq exons, respectively. Uncovered regions with WES included those that are not targeted by the exome capture kit and regions with high GC content. Twelve homozygous mutations in known deafness genes, of which eight are novel, were identified in 12 families: MYO15A-p.Q1425X, -p.S1481P, -p.A1551D; LOXHD1-p.R1494X, -p.E955X; GIPC3-p.H170N; ILDR1-p.Q274X; MYO7A-p.G2163S; TECTA-p.Y1737C; TMC1-p.S530X; TMPRSS3-p.F13Lfs*10; TRIOBP-p.R785Sfs*50. Each mutation was within a homozygous run documented via WES. Sanger sequencing confirmed co-segregation of the mutation with deafness in each family. Four rare heterozygous variants, predicted to be pathogenic, in known deafness genes were detected in 12 families where homozygous causative variants were already identified. Six heterozygous variants that had similar characteristics to those abovementioned variants were present in 15 ethnically-matched individuals with normal hearing. Our results show that rare causative mutations in known ARNSHL genes can be reliably identified via WES. The excess of heterozygous variants should be considered during search for causative mutations in ARNSHL genes, especially in small-sized families. PMID:23226338

  9. 38. RECESSED ARCH DETAIL WITH STONE SCONCE ON FRONT OF ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. RECESSED ARCH DETAIL WITH STONE SCONCE ON FRONT OF 1931 SECTION, PROJECTING SIDE BAY, TAKEN FROM THE NORTH. - James Russell Lowell Elementary School, 4501 Crittenden Drive, Louisville, Jefferson County, KY

  10. Global Recession May Have Contributed to Cancer Deaths

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_159060.html Global Recession May Have Contributed to Cancer Deaths Health- ... THURSDAY, May 26, 2016 (HealthDay News) -- The 2008 global economic crisis has been linked to a sharp ...

  11. Spontaneous improvement of gingival recession after correction of tooth positioning.

    PubMed

    Machado, Andre Wilson; MacGinnis, Matthew; Damis, Lucio; Moon, Won

    2014-06-01

    A 30-year-old woman sought treatment for malpositioned mandibular incisors; the roots were positioned outside the alveolar bone, related to severe localized gingival recession. She had been previously treated orthodontically and subsequently underwent 2 gingival grafts. The new treatment included torquing the roots back within the alveolar bone and referral to a periodontist for a gingival graft. In this clinical report, the possible spontaneous improvement of gingival recession is discussed. A hypothesis described in the literature is called the "creeping attachment" phenomenon. The literature includes conflicting reports about the cause-and-effect relationship between orthodontics and gingival recession. This clinical example reports spontaneous improvement of gingival recession after correction of tooth positioning in the alveolar bone. A gingival graft can be performed after adequate root positioning in the alveolar bone housing, thus increasing the chance of achieving more favorable results. PMID:24880854

  12. 8. Detail view of pierced arch concrete rails and recessed ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    8. Detail view of pierced arch concrete rails and recessed panel railing piers at the west pedestrian alcove, north side of the bridge. - Yellow Mill Bridge, Spanning Yellow Mill Channel at Stratford Avenue, Bridgeport, Fairfield County, CT

  13. 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.

  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. 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.

  16. 6. VIEW OF DISTURBANCE IN THE LOWER GATE RECESS LOOKING ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    6. VIEW OF DISTURBANCE IN THE LOWER GATE RECESS LOOKING NORTHEAST. - Ohio Slack Water Dams, Lock & Dam No. 4, East bank of Ohio River at mile point 18.6, along State Route 65, Ambridge, Beaver County, PA

  17. 9. VIEW OF UPPER LOCK RECESS SHOWING SUBMERGED GATE TRACKS, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    9. VIEW OF UPPER LOCK RECESS SHOWING SUBMERGED GATE TRACKS, LOOKING WEST. - Ohio Slack Water Dams, Lock & Dam No. 4, East bank of Ohio River at mile point 18.6, along State Route 65, Ambridge, Beaver County, PA

  18. 31. DETAILED INTERIOR VIEW OF AUXILIARY LOCK, SHOWING RECESSES FOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    31. DETAILED INTERIOR VIEW OF AUXILIARY LOCK, SHOWING RECESSES FOR MITER GATE OPERATING MACHINERY IN LEFT FOREGROUND. LOOKING NORTHEAST (UPSTREAM) - Upper Mississippi River Nine-Foot Channel Project, Lock & Dam No. 25, Cap au Gris, Lincoln County, MO

  19. 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

  20. Detail of southeast wing wall, facing east. Note recessed panel, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Detail of southeast wing wall, facing east. Note recessed panel, indicative of the stripped classicism style. - Oakland Avenue Viaduct, Oakland Avenue spanning U.S. Route 62 (State Route 2302) & Pine Run, Sharon, Mercer County, PA

  1. Great Recession Linked to Weight Gain in Kids

    MedlinePlus

    ... the negative and lasting health effects of an economic shock like the Great Recession, effects that have ... weight once it is gained, this period of economic hardship could have consequences that last long into ...

  2. 13. POWER CIRCUIT BREAKER, RECESSED IN CABINET BEHIND HINGED METAL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. POWER CIRCUIT BREAKER, RECESSED IN CABINET BEHIND HINGED METAL DOOR (SHOWN OPEN), WEST SIDE, MAIN FLOOR - Bonneville Power Administration South Bank Substation, I-84, South of Bonneville Dam Powerhouse, Bonneville, Multnomah County, OR

  3. Gingival recession: prevalence and risk indicators among young greek adults

    PubMed Central

    2014-01-01

    Objectives: The aim of the current research was to assess the prevalence of gingival recession and to investigate possible associations among this condition, periodontal and epidemiological variables in a sample of young Greek adults in a general dental practice. Material and Methods: A total of 1,430 young adults was examined clinically and interviewed regarding several periodontal and epidemiological variables. Collected data included demographic variables, oral hygiene habits and smoking status. Clinical examination included the recording of dental plaque, supragingival calculus presence, gingival status and buccal gingival recession. Multivariate logistic regression analysis model was performed to access the possible association between gingival recession and several periodontal and epidemiological variables as potential risk factors. Results: The overall prevalence of gingival recession was 63.9%. The statistical analysis indicated that higher educational level [OR= 2.12, 95% CI= 0.53-8.51], cigarette smoking [OR= 1.97, 95% CI= 1.48-7.91], frequent tooth brushing [OR= 0.98, 95% CI= 0.56-1.96], presence of oral piercing [OR= 0.92, 95% CI= 0.38-1.58], presence of gingival inflammation [OR= 4.54, 95% CI= 1.68-7.16], presence of dental plaque [OR= 1.67, 95% CI= 0.68-2.83] and presence of supragingival calculus [OR=1.34, 95% CI= 0.59-1.88], were the most important associated factors of gingival recession. Conclusions: The observations of the current research supported the results from previous authors that several periodontal factors, educational level and smoking were significantly associated with the presence of gingival recession, while presence of oral piercing was a new factor that was found to be associated with gingival recession. Key words:Gingival recession, prevalence, risk factors, young adults. PMID:25136424

  4. 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

  5. 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.

  6. 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

  7. 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…

  8. 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.

  9. A novel autosomal recessive non-syndromic hearing impairment locus (DFNB47) maps to chromosome 2p25.1-p24.3.

    PubMed

    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

    2006-01-01

    Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. Autosomal recessive (AR) forms of prelingual HI account for approximately 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

  10. 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

  11. Novel mutations of endothelin-B receptor gene in Pakistani patients with Waardenburg syndrome.

    PubMed

    Jabeen, Raheela; Babar, Masroor Ellahi; Ahmad, Jamil; Awan, Ali Raza

    2012-01-01

    Mutations in EDNRB gene have been reported to cause Waardenburg-Shah syndrome (WS4) in humans. We investigated 17 patients with WS4 for identification of mutations in EDNRB gene using PCR and direct sequencing technique. Four genomic mutations were detected in four patients; a G to C transversion in codon 335 (S335C) in exon 5 and a transition of T to C in codon (S361L) in exon 5, a transition of A to G in codon 277 (L277L) in exon 4, a non coding transversion of T to A at -30 nucleotide position of exon 5. None of these mutations were found in controls. One of the patients harbored two novel mutations (S335C, S361L) in exon 5 and one in Intronic region (-30exon5 A>G). All of the mutations were homozygous and novel except the mutation observed in exon 4. In this study, we have identified 3 novel mutations in EDNRB gene associated with WS4 in Pakistani patients. PMID:21547364

  12. 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

  13. 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

  14. Restless Legs Syndrome among Pakistani Population: A Cross-Sectional Study

    PubMed Central

    Mahmood, Khalid; Farhan, Rabeea; Surani, Arif Anwer

    2015-01-01

    Objective. Restless leg syndrome (RLS) is a chronic distressing disease characterized by an urge to move the legs with an unpleasantsensation during periods of rest. The global prevalence estimates of RLS range from 2.5% to 15%. Method. This cross-sectional study was conducted at various hospitals in Karachi during August 13 to March 14. The visitors who had accompanied patients to Outpatient Department or had come to visit admitted patients were approached conveniently. Subjects were interviewed regarding the essential criteria of RLS and its attributes. Results. The sample size was 390 with 56% being females. The point prevalence of RLS was estimated to be 23.6%. The prevalence in females was twice as high as compared to males. Smoking and low level of education were associated with RLS (P < 0.001). Among RLS positive individuals, 50.1% reported frequency of their symptoms to be greater than 16 days per month and 64.1% graded their symptom severity as mild to moderate. About 37% of RLS positive individuals consulted a general physician for their symptoms. Conclusion. RLS is highly prevalent and underdiagnosed condition among Pakistani population. Efforts must be directed to raise the awareness of this condition among physicians and general population.

  15. 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.

  16. 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

  17. Indo-Pakistani nuclear issue: A US policy perspective. Master's thesis

    SciTech Connect

    Wolf, J.L.

    1992-06-01

    This thesis examines U.S. nonproliferation policy and the problem of nuclear proliferation in India and Pakistan. Its central hypothesis is that the end of the Cold War has created an opportunity to advance U.S. nonproliferation interests and work with both India and Pakistan to reduce the threat of a nuclear confrontation on the Indian Subcontinent. The thesis assesses both the motives for and the current status of the nuclear weapons programs in India and Pakistan. It also presents some plausible scenarios concerning future courses those programs could take. Finally, it presents a set of policy recommendations directed toward reducing Indo-Pakistani nuclear tensions and laying the foundations to make a future South Asian nuclear nonproliferation regime possible. Ultimately, this approach would create safer, more stable security arrangements for India and Pakistan and further reduce the threat from nuclear weapons in the post-Cold War world. United States, India, Pakistan, U.S.-Indian Relations, U.S.-Pakistan Relations, Nuclear Weapons, Nonproliferation, U.S. Foreign Policy.

  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. Allele frequency distribution of 13 X-chromosomal STR loci in Pakistani population.

    PubMed

    Tariq, Muhammad Akram; Ullah, Obaid; Riazuddin, S Amer; Riazuddin, Sheikh

    2008-11-01

    Short tandem repeat (STR) markers are extensively being used for human identification as well as paternity and forensic case work. X-chromosome STR (X-STR) markers are a powerful complementary system especially in deficiency paternity testing. Many X-linked microsatellites have been evaluated but further studies are required to determine population specific statistics. Here, we report allele frequencies of 13 X-linked microsatellites (DXS8378, DXS9902, DXS6810, DXS7132, DXS981, DXS6793, DXS6801, DXS6789, GATA172D05, HPRTB, GATA31E08, DXS8377, and DXS7423) in the Pakistani population. Blood samples were collected from individuals representing all major ethnic groups of the Pakistan population. A total of 5-18 alleles were observed for each locus and altogether 109 alleles for all 13 X-STR loci. Heterozygosity in females ranged from 0.524 to 0.884. No significant deviation was observed from Hardy-Weinberg equilibrium for all 13 microsatellites. In addition, there was no evidence of linkage disequilibrium in any pairs of these markers. These results strongly suggest that the X-linked microsatellites described here can potentially serve as an extension to autosomal systems currently used in parentage analysis and forensic case work. PMID:18629532

  20. 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…

  1. 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

  2. Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.

    PubMed

    Schlingmann, Karl P; Ruminska, Justyna; Kaufmann, Martin; Dursun, Ismail; Patti, Monica; Kranz, Birgitta; Pronicka, Ewa; Ciara, Elzbieta; Akcay, Teoman; Bulus, Derya; Cornelissen, Elisabeth A M; Gawlik, Aneta; Sikora, Przemysław; Patzer, Ludwig; Galiano, Matthias; Boyadzhiev, Veselin; Dumic, Miroslav; Vivante, Asaf; Kleta, Robert; Dekel, Benjamin; Levtchenko, Elena; Bindels, René J; Rust, Stephan; Forster, Ian C; Hernando, Nati; Jones, Glenville; Wagner, Carsten A; Konrad, Martin

    2016-02-01

    Idiopathic infantile hypercalcemia (IIH) is characterized by severe hypercalcemia with failure to thrive, vomiting, dehydration, and nephrocalcinosis. Recently, mutations in the vitamin D catabolizing enzyme 25-hydroxyvitamin D3-24-hydroxylase (CYP24A1) were described that lead to increased sensitivity to vitamin D due to accumulation of the active metabolite 1,25-(OH)2D3. In a subgroup of patients who presented in early infancy with renal phosphate wasting and symptomatic hypercalcemia, mutations in CYP24A1 were excluded. Four patients from families with parental consanguinity were subjected to homozygosity mapping that identified a second IIH gene locus on chromosome 5q35 with a maximum logarithm of odds (LOD) score of 6.79. The sequence analysis of the most promising candidate gene, SLC34A1 encoding renal sodium-phosphate cotransporter 2A (NaPi-IIa), revealed autosomal-recessive mutations in the four index cases and in 12 patients with sporadic IIH. Functional studies of mutant NaPi-IIa in Xenopus oocytes and opossum kidney (OK) cells demonstrated disturbed trafficking to the plasma membrane and loss of phosphate transport activity. Analysis of calcium and phosphate metabolism in Slc34a1-knockout mice highlighted the effect of phosphate depletion and fibroblast growth factor-23 suppression on the development of the IIH phenotype. The human and mice data together demonstrate that primary renal phosphate wasting caused by defective NaPi-IIa function induces inappropriate production of 1,25-(OH)2D3 with subsequent symptomatic hypercalcemia. Clinical and laboratory findings persist despite cessation of vitamin D prophylaxis but rapidly respond to phosphate supplementation. Therefore, early differentiation between SLC34A1 (NaPi-IIa) and CYP24A1 (24-hydroxylase) defects appears critical for targeted therapy in patients with IIH. PMID:26047794

  3. Whole-Exome Sequencing Identifies Mutations in GPR179 Leading to Autosomal-Recessive Complete Congenital Stationary Night Blindness

    PubMed Central

    Audo, Isabelle; Bujakowska, Kinga; Orhan, Elise; Poloschek, Charlotte M.; Defoort-Dhellemmes, Sabine; Drumare, Isabelle; Kohl, Susanne; Luu, Tien D.; Lecompte, Odile; Zrenner, Eberhart; Lancelot, Marie-Elise; Antonio, Aline; Germain, Aurore; Michiels, Christelle; Audier, Claire; Letexier, Mélanie; Saraiva, Jean-Paul; Leroy, Bart P.; Munier, Francis L.; Mohand-Saïd, Saddek; Lorenz, Birgit; Friedburg, Christoph; Preising, Markus; Kellner, Ulrich; Renner, Agnes B.; Moskova-Doumanova, Veselina; Berger, Wolfgang; Wissinger, Bernd; Hamel, Christian P.; Schorderet, Daniel F.; De Baere, Elfride; Sharon, Dror; Banin, Eyal; Jacobson, Samuel G.; Bonneau, Dominique; Zanlonghi, Xavier; Le Meur, Guylene; Casteels, Ingele; Koenekoop, Robert; Long, Vernon W.; Meire, Francoise; Prescott, Katrina; de Ravel, Thomy; Simmons, Ian; Nguyen, Hoan; Dollfus, Hélène; Poch, Olivier; Léveillard, Thierry; Nguyen-Ba-Charvet, Kim; Sahel, José-Alain; Bhattacharya, Shomi S.; Zeitz, Christina

    2012-01-01

    Congenital stationary night blindness (CSNB) is a heterogeneous retinal disorder characterized by visual impairment under low light conditions. This disorder is due to a signal transmission defect from rod photoreceptors to adjacent bipolar cells in the retina. Two forms can be distinguished clinically, complete CSNB (cCSNB) or incomplete CSNB; the two forms are distinguished on the basis of the affected signaling pathway. Mutations in NYX, GRM6, and TRPM1, expressed in the outer plexiform layer (OPL) lead to disruption of the ON-bipolar cell response and have been seen in patients with cCSNB. Whole-exome sequencing in cCSNB patients lacking mutations in the known genes led to the identification of a homozygous missense mutation (c.1807C>T [p.His603Tyr]) in one consanguineous autosomal-recessive cCSNB family and a homozygous frameshift mutation in GPR179 (c.278delC [p.Pro93Glnfs∗57]) in a simplex male cCSNB patient. Additional screening with Sanger sequencing of 40 patients identified three other cCSNB patients harboring additional allelic mutations in GPR179. Although, immunhistological studies revealed Gpr179 in the OPL in wild-type mouse retina, Gpr179 did not colocalize with specific ON-bipolar markers. Interestingly, Gpr179 was highly concentrated in horizontal cells and Müller cell endfeet. The involvement of these cells in cCSNB and the specific function of GPR179 remain to be elucidated. PMID:22325361

  4. 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

  5. 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

  6. A novel CHST3 allele associated with spondyloepiphyseal dysplasia and hearing loss in Pakistani kindred.

    PubMed

    Waryah, A M; Shahzad, M; Shaikh, H; Sheikh, S A; Channa, N A; Hufnagel, R B; Makhdoom, A; Riazuddin, S; Ahmed, Z M

    2016-07-01

    Skeletal dysplasias (SDs) are highly heterogeneous disorders composed of 40 clinical sub-types that are part of 456 well-delineated syndromes in humans. Here, we enrolled consanguineous kindred from a remote area of Sindh province of Pakistan, with 14 affected individuals suffering with short stature, kyphoscoliosis, joint dislocations, clubfoot, heart valve anomalies and progressive bilateral mixed hearing loss. To identify pathogenic variants in this family, whole exome sequencing (WES) was performed in one affected and one normal individual, which revealed a novel transversion mutation (c.802G>T; p.Glu268*) in CHST3 associated with the phenotype. CHST3 encodes a chondroitin 6-O-sulfotransferase-1 (C6ST-1) enzyme that is essential for the sulfation of proteoglycans found in cartilages. Previously, mutations in CHST3 have largely been reported in sporadic cases of SD, primarily with severe spinal abnormalities, joint dislocations, joint contractures, and clubfoot. Clinical and radiological examination of the affected individuals in this family provides new insights into phenotypic spectrum of CHST3 alleles and disease progression with age. PMID:26572954

  7. 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

  8. Molecular analysis of human leukocyte antigen class I and class II allele frequencies and haplotype distribution in Pakistani population

    PubMed Central

    Moatter, T.; Aban, M.; Tabassum, S.; Shaikh, U.; Pervez, S.

    2010-01-01

    AIM: Distribution of HLA class I and II alleles and haplotype was studied in Pakistani population and compared with the data reported for Caucasoid, Africans, Orientals and Arab populations. MATERIALS AND METHODS: HLA class I and II polymorphisms in 1000 unrelated Pakistani individuals was studied using sequence-specific primers and polymerase chain reaction and assay. RESULTS: The most frequent class I alleles observed were A*02, B*35 and CW*07, with frequencies of 19.2, 13.7 and 20%, respectively. Fifteen distinct HLA-DRB1 alleles and eight HLA-DQB1 alleles were recognized. The most frequently observed DRB1 alleles which represented more than 60% of the subjects were DRB1 *03, *07, *11 and *15. The rare DRB1 alleles detected in this study were HLADRB1 *08 and *09, having frequencies of 0.9 and 1.7%, respectively. In addition, at DRB1-DQB1 loci there were 179 different haplotypes and 285 unique genotypes and the most common haplotype was DRB1*15-DQB1*06 which represented 17% of the total DRB1-DQB1 haplotypes. In our population, haplotype A*33-B*58-Cw*03 comprised 2.8% of the total class I haplotypes observed. This haplotype was seen only in the oriental populations and has not been reported in the African or European Caucasoid. CONCLUSION: Our study showed a close similarity of HLA class I and II alleles with that of European Caucasoid and Orientals. In Pakistani population, two rare loci and three haplotypes were identified, whereas haplotypes characteristic of Caucasians, Africans and Orientals were also found, suggesting an admixture of different races due to migration to and from this region. PMID:21206703

  9. A compound heterozygote SLC26A2 mutation resulting in robin sequence, mild limbs shortness, accelerated carpal ossification, and multiple epiphysial dysplasia in two Brazilian sisters. A new intermediate phenotype between diastrophic dysplasia and recessive multiple epiphyseal dysplasia.

    PubMed

    Zechi-Ceide, Roseli Maria; Moura, Priscila Padilha; Raskin, Salmo; Richieri-Costa, Antonio; Guion-Almeida, Maria Leine

    2013-08-01

    Mutations in solute carrier family 26 (sulfate transporter), member 2 (SLC26A2) gene result in a spectrum of autosomal recessive chondrodysplasias that range from the mildest recessive form of multiple epiphysial dysplasia (rMED) through the most common diastrophic dysplasia (DTD) to lethal atelosteogenesis type II and achondrogenesis IB. The clinical variability has been ascribed to quantitative effect of mutations of the sulfate transporter activity. Here we describe two Brazilian sisters, born to healthy and non consanguineous parents, with Robin sequence, mild shortening of upper and lower limbs, brachymetacarpalia/tarsalia, additional and accelerated carpal ossification, marked genu valgum, and multiple epiphysial dysplasia. This phenotype was intermediate between DTD and rMED, and both girls have a compound heterozygous mutations for the SLC26A2, a Finnish founder mutation (c.-26 + 2T>C), and R279W. This combination of mutations has been observed in individuals with different phenotypes, including DTD, DTD variant, and rMED. The distinct phenotype of our cases reinforces the hypothesis that other factors may be influencing the phenotype as previously suggested. PMID:23840040

  10. WDR19: An ancient, retrograde, intraflagellar ciliary protein is mutated in autosomal recessive retinitis pigmentosa and in Senior-Loken syndrome

    PubMed Central

    Coussa, RG; Otto, EA; Gee, H-Y; Arthurs, P; Ren, H; Lopez, I; Keser, V; Fu, Q; Faingold, R; Khan, A; Schwartzentruber, J; Majewski, J; Hildebrandtand, F; Koenekoop, RK

    2014-01-01

    Autosomal recessive retinitis pigmentosa (arRP) is a clinically and genetically heterogeneous retinal disease that causes blindness. Our purpose was to identify the causal gene, describe the phenotype and delineate the mutation spectrum in a consanguineous Quebec arRP family. We performed Arrayed Primer Extension (APEX) technology to exclude ~500 arRP mutations in ~20 genes. Homozygosity mapping [single nucleotide polymorphism (SNP) genotyping] identified 10 novel significant homozygous regions. We performed next generation sequencing and whole exome capture. Sanger sequencing provided cosegregation. We screened another 150 retinitis pigmentosa (RP) and 200 patients with Senior-Løken Syndrome (SLS). We identified a novel missense mutation in WDR19, c.2129T>C which lead to a p.Leu710Ser. We found the same mutation in a second Quebec arRP family. Interestingly, two of seven affected members of the original family developed ‘sub-clinical’ renal cysts. We hypothesized that more severe WDR19 mutations may lead to severe ciliopathies and found seven WDR19 mutations in five SLS families. We identified a new gene for both arRP and SLS. WDR19 is a ciliary protein associated with the intraflagellar transport machinery. We are currently investigating the full extent of the mutation spectrum. Our findings are crucial in expanding the understanding of childhood blindness and identifying new genes. PMID:23683095

  11. Autosomal recessive multiple epiphyseal dysplasia with homozygosity for C653S in the DTDST gene: double-layer patella as a reliable sign.

    PubMed

    Mäkitie, Outi; Savarirayan, Ravi; Bonafé, Luisa; Robertson, Stephen; Susic, Miki; Superti-Furga, Andrea; Cole, William G

    2003-10-15

    Mutations in the diastrophic dysplasia sulfate transporter (DTDST) gene result in a family of skeletal dysplasias, which comprise lethal (achondrogenesis type 1B and atelosteogenesis type 2) and non-lethal conditions (diastrophic dysplasia and recessive multiple epiphyseal dysplasia (rMED)). The most frequent mutation is R279W, which in a homozygous state results in rMED with bilateral clubfoot, MED, and "double layered" patella. We describe three patients with rMED caused by a previously unreported homozygous mutation in the DTDST gene. The three patients (from two families) were born to healthy, non-consanguineous parents. All developed signs of hip dysplasia in early childhood and two had episodes of recurrent patella dislocation. Two underwent bilateral total hip replacements at ages 13 and 14 years. The feet, external ears, and palate were normal. Stature was normal in all cases. Radiographs showed dysplastic femoral heads, mild generalized epiphyseal dysplasia, abnormal patella ossification, and normal hands and feet. Direct sequence analysis of genomic DNA demonstrated a homozygous 1984T > A (C653S) change in the DTDST gene in all patients. The clinically normal parents were heterozygous for the change. This is the first description of a homozygous C653S mutation of the DTDST gene. Hip dysplasia and patella hypermobility dominates the otherwise mild phenotype. These patients further expand the range of causative mutations in the DTD skeletal dysplasia family. PMID:12966518

  12. SIPA1L3 identified by linkage analysis and whole-exome sequencing as a novel gene for autosomal recessive congenital cataract.

    PubMed

    Evers, Christina; Paramasivam, Nagarajan; Hinderhofer, Katrin; Fischer, Christine; Granzow, Martin; Schmidt-Bacher, Annette; Eils, Roland; Steinbeisser, Herbert; Schlesner, Matthias; Moog, Ute

    2015-12-01

    Congenital cataract (CC) is one of the most important causes for blindness or visual impairment in infancy. A substantial proportion of isolated CCs has monogenic causes. The disease is genetically heterogeneous, and all Mendelian modes of inheritance have been reported. We mapped a locus for isolated CC on 19p13.1-q13.2 in a distantly consanguineous German family with two sisters affected by dense white cataracts. Whole-exome sequencing identified a homozygous nonsense variant c.4489C>T (p.(R1497*)) in SIPA1L3 (signal-induced proliferation-associated 1 like 3) in both affected children. SIPA1L3 encodes a GTPase-activating protein (GAP), which interacts with small GTPases of the Rap family via its Rap-GAP-domain. The suggested role of Rap GTPases in cell growth, differentiation and organization of the cytoskeleton in the human lens, and lens-enriched expression of the murine ortholog gene Sipa1l3 in embryonic mice indicates that this gene is crucial for early lens development. Our results provide evidence that sequence variants in human SIPA1L3 cause autosomal recessive isolated CC and give new insight into the molecular pathogenesis underlying human cataracts. PMID:25804400

  13. Homozygous Truncating Intragenic Duplication in TUSC3 Responsible for Rare Autosomal Recessive Nonsyndromic Intellectual Disability with No Clinical or Biochemical Metabolic Markers.

    PubMed

    El Chehadeh, S; Bonnet, C; Callier, P; Béri, M; Dupré, T; Payet, M; Ragon, C; Mosca-Boidron, A L; Marle, N; Mugneret, F; Masurel-Paulet, A; Thevenon, J; Seta, N; Duplomb, L; Jonveaux, P; Faivre, L; Thauvin-Robinet, C

    2015-01-01

    Intellectual disability (ID), which affects around 2-3% of the general population, is classically divided into syndromic and nonsyndromic forms, with several modes of inheritance. Nonsyndromic autosomal recessive ID (NS-ARID) appears extremely heterogeneous with numerous genes identified to date, including inborn errors of metabolism. The TUSC3 gene encodes a subunit of the endoplasmic reticulum (ER)-bound oligosaccharyltransferase complex, which mediates a key step of N-glycosylation. To date, only five families with NS-ARID and TUSC3 mutations or rearrangements have been reported in the literature. All patients had speech delay, moderate-to-severe ID, and moderate facial dysmorphism. Microcephaly was noted in one third of patients, as was short stature. No patients had congenital malformation except one patient with unilateral cryptorchidism. Glycosylation analyses of patients' fibroblasts showed normal N-glycan synthesis and transfer. We present a review of the 19 patients previously described in the literature and report on a sixth consanguineous family including two affected sibs, with intellectual disability, unspecific dysmorphic features, and no additional malformations identified by high-resolution array-CGH. A homozygous truncating intragenic duplication of the TUSC3 gene leading to an aberrant transcript was detected in two siblings. This observation, which is the first reported case of TUSC3 homozygous duplication, confirms the implication of TUSC3 in NS-ARID and the power of the high-resolution array-CGH in identifying intragenic rearrangements of genes implicated in nonsyndromic ID and rare diseases. PMID:25626710

  14. Mutations in CDC14A, Encoding a Protein Phosphatase Involved in Hair Cell Ciliogenesis, Cause Autosomal-Recessive Severe to Profound Deafness.

    PubMed

    Delmaghani, Sedigheh; Aghaie, Asadollah; Bouyacoub, Yosra; El Hachmi, Hala; Bonnet, Crystel; Riahi, Zied; Chardenoux, Sebastien; Perfettini, Isabelle; Hardelin, Jean-Pierre; Houmeida, Ahmed; Herbomel, Philippe; Petit, Christine

    2016-06-01

    By genetic linkage analysis in a large consanguineous Iranian family with eleven individuals affected by severe to profound congenital deafness, we were able to define a 2.8 Mb critical interval (at chromosome 1p21.2-1p21.1) for an autosomal-recessive nonsyndromic deafness locus (DFNB). Whole-exome sequencing allowed us to identify a CDC14A biallelic nonsense mutation, c.1126C>T (p.Arg376(∗)), which was present in the eight clinically affected individuals still alive. Subsequent screening of 115 unrelated individuals affected by severe or profound congenital deafness of unknown genetic cause led us to identify another CDC14A biallelic nonsense mutation, c.1015C>T (p.Arg339(∗)), in an individual originating from Mauritania. CDC14A encodes a protein tyrosine phosphatase. Immunofluorescence analysis of the protein distribution in the mouse inner ear showed a strong labeling of the hair cells' kinocilia. By using a morpholino strategy to knockdown cdc14a in zebrafish larvae, we found that the length of the kinocilia was reduced in inner-ear hair cells. Therefore, deafness caused by loss-of-function mutations in CDC14A probably arises from a morphogenetic defect of the auditory sensory cells' hair bundles, whose differentiation critically depends on the proper growth of their kinocilium. PMID:27259055

  15. Biallelic Truncating Mutations in FMN2, Encoding the Actin-Regulatory Protein Formin 2, Cause Nonsyndromic Autosomal-Recessive Intellectual Disability

    PubMed Central

    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.

    2014-01-01

    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. PMID:25480035

  16. Molecular bases of autosomal recessive limb-girdle muscular dystrophies.

    PubMed

    Nigro, V

    2003-09-01

    Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically determined disorders with a primary or predominant involvement of the pelvic or shoulder girdle musculature. The clinical course is characterized by great variability, ranging from severe forms with rapid onset and progression to very mild forms allowing affected people to have fairly normal life spans and activity levels. Sixteen loci have been so far identified, six autosomal dominant and ten autosomal recessive. Linkage analyses indicate that there is further genetic heterogeneity both for dominant as well as for recessive LGMD. The dominant forms (LGMD1) are generally milder and relatively rare, representing less than 10% of all LGMD. The autosomal recessive forms (LGMD2) are much more common, having a cumulative prevalence of 1:15,000 with a number of geographical differences. The product of ten autosomal recessive LGMD genes has so far been identified. They are: calpain-3 (LGMD2A), dysferlin (LGMD2B), alpha-sarcoglycan (LGMD2D), beta-sarcoglycan (LGMD2E), gamma-sarcoglycan (LGMD2C), delta-sarcoglycan (LGMD2F), telethonin (LGMD2G), TRIM32 (LGMD2H), fukutin-related protein (LGMD2I) and titin (LGMD2J). There are, however, at least 25% of families who can be excluded from any known locus. The present review is devoted to outline the present advancements in the molecular bases of autosomal recessive LGMD. PMID:14959561

  17. Ecology and Management of the Spring Snowmelt Recession

    NASA Astrophysics Data System (ADS)

    Yarnell, S.; Viers, J. H.; Mount, J. F.

    2009-12-01

    We present a conceptual model for the ecology of the spring snowmelt recession, delineating components of the natural flow regime most relevant to the recession hydrograph and their relation to physical and biological stream processes. Using general principles to describe expected responses in stream ecosystems, we specifically relate the quantifiable components of magnitude, timing and rate of change to abiotic and biotic factors that govern aquatic and riparian ecosystem functioning. We find that shifts in the magnitude of the start of the recession have the largest impacts on abiotic conditions in the channel, while shifts in the timing primarily affect biotic conditions. Shifts in the rate of change of the recession impact both abiotic and biotic conditions, creating the largest observed changes to the stream ecosystem. We discuss these spring hydrograph components with regard to the success of native riverine species, such as cottonwood (Populus spp.) and the Foothill yellow-legged frog (Rana boylii), an indicator species for instream biota in the Mediterranean-montane environment of California. We then present two scenarios of change to the spring snowmelt recession and discuss their potential implications for general stream ecology: 1) effects of flow regulation, and 2) effects of climate warming. Our conceptual model can help guide water resource managers to more effectively maintain key ecosystem processes in regulated rivers, and help watershed stakeholders form adaptation strategies for anticipated changes in the nature of flow regimes due to climate warming.

  18. Facial soft tissue thickness among various vertical facial patterns in adult Pakistani subjects.

    PubMed

    Jeelani, Waqar; Fida, Mubassar; Shaikh, Attiya

    2015-12-01

    Facial reconstruction techniques are used to obtain an approximation of an individual's appearance thus helping identification of unidentified decedents from their dried skeletal remains. Many of these techniques rely on the sets of average facial soft tissue thickness (FST) values at different anatomical landmarks provided by the previous studies. FST is influenced by the age, sex, ethnicity and the body mass index of the individual. Recent literature has shown that the anthropological variations of the skull may also affect FST at certain points. This study was designed to evaluate the effect of such variations in vertical skull morphology on FST as around one third of different population groups have either a long or short facial pattern as compared to the average facial pattern. Moreover, this study also provides a FST database for the adult Pakistani subjects that may have potential implications in the facial reconstruction of the local subjects. A retrospective analysis of 276 lateral cephalograms of adult subjects having normal sagittal facial pattern was performed. Subjects were categorized into three vertical facial patterns (long face=95, average face=102, short face=79) according to the vertical dimensions of the skull and the FST was measured at 11 midline points. To compare the FST between males and females Mann-Whitney U test was used. Kruskal-Wallis test was applied to compare FST among three vertical facial patterns. The results of our study revealed significant differences in FST at nine landmarks between males and females. These sex-based differences were more pronounced in the long and short facial patterns as compared to the average facial pattern. FST at stomion, pogonion, gnathion and menton was significantly greater in the short facial pattern as compared to the long facial pattern in both the sexes. The results of the present study highlight the importance of anthropological analysis of the skull and taking the vertical skeletal dimension

  19. Clinical, lifestyle, socioeconomic determinants and rate of asymptomatic intracranial atherosclerosis in stroke free Pakistanis

    PubMed Central

    2014-01-01

    Background Intracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region. Methods The study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used in the Warfarin–Aspirin Symptomatic Intracranial Disease study. The risk factors associated with asymptomatic ICAD are reported along with prevalence ratios. Results Of the 200 participants, ICAD was found in 34.5% (n = 69) of the participants. Mean age was 37.1 (S.D 15.1) years with 62% younger than 45 years. Self-reported hypertension was found in 26.5% subjects, diabetes in 9%, dyslipidemia in 5% and depression in 60%. Smokeless tobacco (Adjusted PR 3.27 (1.07-6.05)), Western diet, high socioeconomic status (Adjusted PR 2.26 (1.99-5.62)) and dyslipidemia (Adjusted PR 1.88 (1.25-2.21)) had significant associations with ICAD after multivariable analysis. Age, gender, diabetes, hypertension, depression and physical activity did not have a significant association. Conclusion ICAD was found on MRI in one in three asymptomatic Pakistanis and was associated with modifiable risks. Initiatives targeting primary prevention may be able to decrease the burden of disease caused by stroke due to ICAD. Study Registration Number NCT02072876 2/25/2014 PMID:25124284

  20. Chloroquine resistance in Pakistan and the upsurge of falciparum malaria in Pakistani and Afghan refugee populations.

    PubMed

    Shah, I; Rowland, M; Mehmood, P; Mujahid, C; Razique, F; Hewitt, S; Durrani, N

    1997-09-01

    Surveys conducted in Pakistan during the last decade show that falciparum malaria has become resistant to chloroquine in Pakistani and Afghan refugee populations throughout the country. Although RI resistance is common everywhere (with a frequency of 30%-84%), RII is rarer (2%-36%), and RIII resistance has yet to be detected. The national policy is to prescribe chloroquine as first-line treatment of malaria. A repeated in-vivo survey in a sentinel village indicated that prescription of chloroquine can lead to a 15% increase in the frequency of resistance in a single year, and similar trends were observed in other districts. Coinciding with the spread of resistance is a 6-fold increase in the number of falciparum cases recorded nationally between 1982 and 1992 and a parallel, 5-fold increase in the number of cases recorded in the Afghan refugee population. Resistance contributes to this trend in various ways. Firstly, patients with resistant malaria make repeated visits to health centres. In the sentinel village, for example, where resistance was measured at 71%, recrudescent infections inflated by 66% the genuine incidence of new infections recorded at the health centre. Secondly, owing to ineffective treatment, resistant infections are often still patent during the post-transmission season. This may enlarge the 'overwintering' parasite reservoir, leading to a surge of new cases when transmission resumes. Other factors potentially contributing to the upsurge in falciparum include the decrease availability of insecticide for indoor spraying. Despite the problems posed by resistance for case management, the evidence from the vector-control programme among the refugees is that malaria control through well-targeted campaigns of insecticide spraying is still able to reduce the incidence of falciparum malaria to a level that existed before the advent of resistance. PMID:9425361

  1. Is social exclusion pushing the Pakistani Hijras (Transgenders) towards commercial sex work? a qualitative study

    PubMed Central

    2012-01-01

    Background The Hijra is a distinct type of gender role in South Asia where men act like women. This group of people is socially excluded by the general community, in terms of attainment of an opportunity for a socially productive life. Often this sort of deprivation forces these individuals towards professions like sex trade, in pursuit of sustenance, which as a consequence places them as a key block in the puzzle of an impending generalized HIV epidemic in Pakistan. Methods This study is a qualitative study, which involved 8 in-depth interviews and four focus group discussions, conducted in Rawalpindi and Islamabad (Pakistan) from February to April 2012. The data was audio taped and transcribed. Key themes were identified and built upon. The respondents were contacted through a gate keeper Hijra who was a member of the hijra community. Multiple interview sessions were conducted with each respondent. Results Two key categories of the Hijras were identified as Khusrapan and Zananapan, during the in-depth interview sessions. This initial information paved way for the four focus group discussions. The data was presented using key themes which were identified. The study participants explained their life histories to us which made it obvious that they had been socially excluded at many stages of their lives from performing normal social functions. This lack of occupational and educational opportunities pushed them towards entering the risky business of selling sex. Conclusion The transgender community is socially excluded by the Pakistani society which is leading them to indulge in commercial sex and putting their lives at risk. Prudent measures are needed to form community based organizations managed and led by hijra community and addressing their social exclusion and risky behaviors. PMID:23163979

  2. Confirmation of TENM3 involvement in autosomal recessive colobomatous microphthalmia.

    PubMed

    Chassaing, Nicolas; Ragge, Nicola; Plaisancié, Julie; Patat, Oliver; Geneviève, David; Rivier, François; Malrieu-Eliaou, Claudie; Hamel, Christian; Kaplan, Josseline; Calvas, Patrick

    2016-07-01

    Anophthalmia and microphthalmia are the most severe malformations of the eye, referring to a congenital absence, and a reduced size of the eyeball respectively. More than 20 genes have been shown to be mutated in patients with syndromic and non-syndromic forms of anophthalmia-microphthalmia. In a recent study combining autozygome and exome analysis, a homozygous loss of function mutation in TENM3 (previously named ODZ3) was reported in two siblings with isolated bilateral colobomatous microphthalmia from a consanguineous Saudi family. Herein, we report a third patient (not related to the previously reported family) with bilateral colobomatous microphthalmia and developmental delay in whom genetic studies identified a homozygous TENM3 splicing mutation c.2968-2A>T (p.Val990Cysfs*13). This report supports the association of TENM3 mutations with colobomatous microphthalmia and expands the phenotypic spectrum associated with mutations in this gene. © 2016 Wiley Periodicals, Inc. PMID:27103084

  3. The Great Recession, somatic symptomatology and alcohol use and abuse.

    PubMed

    Vijayasiri, Ganga; Richman, Judith A; Rospenda, Kathleen M

    2012-09-01

    While most research has examined the long-term effects of alcohol consumption on health, the current study examines how health status impacts on drinking behavior. Using data from a national study conducted between 2010 and 2011 to assess the impact of the recession on drinking behavior, this study examines how economic hardships linked to the recent economic recession affect physical health, and how physical health may in turn affect alcohol use. Structural equation models were used to test the predicted associations. The data demonstrate that many of the economic stressors linked to the recession are associated with increased somatic symptoms. Somatic symptoms are also associated with increased drinking for men, but not for women. These findings suggest that men may use alcohol to self medicate somatic symptomatology. The current findings are consistent with gender role-based explanations that account for gender disparities in the utilization of medical care. PMID:22632797

  4. 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

  5. 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

  6. Dominant-and-recessive epistasis in a homeotic mosquito mutant.

    PubMed

    Bhalla, S C

    1976-12-01

    Following selection for 15 generations a pure strain of a homeotic mutant spur was isolated from a Brazilian population of the mosquito Culex pipiens fatigans. Monohybrid crosses showed a 13:3 segregation indicating dominant-and-recessive epistasis for wild-type vs. spur. This implies that a dominant allele at one locus and a recessive at the other interact to produce the mutant phenotype. Dihybrid crosses with linkage group II markers yellow and ruby gave 39:13:9:3 ratios indicating independent segregation. However, the dihybrid cross with linkage group I marker maroon showed a highly significant departure from 39:13:9:3 ratio. Data available indicate that the phenotype spur is controlled by a dominant epistat in linkage group III and a recessive epistat (approximately 31.9 crossover units from maroon) in linkage group I. PMID:1022329

  7. Autosomal Recessive Polycystic Kidney Disease: Antenatal Diagnosis and Histopathological Correlation

    PubMed Central

    Rajanna, Dayananda Kumar; Reddy, Anjani; Srinivas, Naren Satya; Aneja, Ankur

    2013-01-01

    Autosomal recessive polycystic kidney disease (ARPKD) is one of the most common inheritable disease manifesting in infancy and childhood with a frequency of 1:6,000 to 1:55,000 births. The patient in her second trimester presented with a history of amenorrhea. Ultrasound examination revealed bilateral, enlarged, hyperechogenic kidneys, placentomegaly, and severe oligohydramnios. The pregnancy was terminated. An autopsy was performed on the fetus. Both the kidneys were found to be enlarged and the cut surface showed numerous cysts. The liver sections showed changes due to fibrosis. The final diagnosis of autosomal recessive polycystic kidney disease was made based on these findings. In this article, we correlate the ante-natal ultrasound and histopathological findings in autosomal recessive polycystic kidney disease. PMID:23814685

  8. 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.

  9. The Great Recession, Somatic Symptomatology and Alcohol Use and Abuse

    PubMed Central

    Vijayasiri, Ganga; Richman, Judith A.; Rospenda, Kathleen M.

    2012-01-01

    While most research has examined the long-term effects of alcohol consumption on health, the current study examines how health status impacts on drinking behavior. Using data from a national study conducted between 2010 and 2011 to assess the impact of the recession on drinking behavior, this study examines how economic hardships linked to the recent economic recession affect physical health, and how physical health may in turn affect alcohol use. Structural equation models were used to test the predicted associations. The data demonstrate that many of the economic stressors linked to the recession are associated with increased somatic symptoms. Somatic symptoms are also associated with increased drinking for men, but not for women. These findings suggest that men may use alcohol to self medicate somatic symptomatology. The current findings are consistent with gender role-based explanations that account for gender disparities in the utilization of medical care. PMID:22632797

  10. 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

  11. Myalgias or non-specific muscle pain in Arab or Indo-Pakistani patients may indicate vitamin D deficiency.

    PubMed

    Badsha, Humeira; Daher, Mirna; Ooi Kong, Kok

    2009-08-01

    The aim of our study was to determine the prevalence of vitamin D deficiency (<20 ng/dl) among patients with fibromyalgia or muscle pain in a musculoskeletal clinic in the United Arab Emirates. Consecutive patients who were diagnosed with fibromyalgia and/or non-specific musculoskeletal pain (ICD-9 729.1) were screened for vitamin D deficiency. Patients were seen at follow-up after treatment with vitamin D was given. Improvement was assessed by a simple questionnaire. Patients (139) with muscle pain were seen in 2007. Average age was 40 +/- year; 95% were female; 69 (49%) were Arab, of whom 92% were veiled; 43 (30%) Indian of whom 11% were veiled; 23 (16%) were Caucasian; and four were East Asian (3%) and all wore western clothes. One hundred three (74%) of these patients had a low vitamin D level. Vitamin D deficiency was most common among Arab patients (86%) and Indo-Pakistani (87%) and least common among the Caucasians (8%) and was equally prevalent among veiled and non-veiled patients. Treatment resulted in clinical improvement in 90% of patients. Non-specific muscle pains among Arab and Indian-Pakistani populations may indicate vitamin D deficiency, and prompt treatment can result in resolution of symptoms. PMID:19277814

  12. Cooperative Monitoring Center Occasional Paper/6: Pakistani Perceptions and Prospects of Reducing the Nuclear Danger in South Asia

    SciTech Connect

    Kamal, N.

    1999-01-01

    The Indian and Pakistani nuclear tests in May 1998 triggered a full-blown nuclear debate. For the first time, hard-liners, moderates, and pacifists engaged in an extensive public discussion that helped to make the people of Pakistan more sensitive to the dangers of nuclear competition. Pakistan's concerns about its conventional military inferiority, both in the present and future, and the belief that nuclear capability would deter India from exerting its superior military strength, constituted the bedrock of its perception on the nuclear issue. Ofilcial Pakistani statements, both immediately after the nuclear tests and later, have advocated restraint on the issue of nuclearization, indicating cognizance of the importance of avoiding a regional nuclear arms competition, both for security and economic reasons. This paper suggests a variety of nonweaponization and nondeployment options that would serve the security interests of India and Pakistan. Besides preventing a hair-trigger situation, these options could reduce the financial and logistical burden of ensuring the safety and security of nuclear weapons as well as lower strategic threat-perceptions.

  13. Dietary education must fit into everyday life: a qualitative study of people with a Pakistani background and type 2 diabetes

    PubMed Central

    Hempler, Nana F; Nicic, Sara; Ewers, Bettina; Willaing, Ingrid

    2015-01-01

    Background The high prevalence of diabetes among South Asian populations in European countries partially derives from unhealthy changes in dietary patterns. Limited studies address perspectives of South Asian populations with respect to utility of diabetes education in everyday life. This study explores perspectives on dietary diabetes education and healthy food choices of people living in Denmark who have a Pakistani background and type 2 diabetes. Methods In-depth interviews were conducted between October 2012 and December 2013 with 12 participants with type 2 diabetes who had received dietary diabetes education. Data analysis was systematic and was based on grounded theory principles. Results Participants described the process of integrating and utilizing dietary education in everyday life as challenging. Perceived barriers of the integration and utilization included a lack of a connection between the content of the education and life conditions, a lack of support from their social networks for dietary change, difficulty integrating the education into everyday life, and failure to include the participants’ taste preferences in the educational setting. Conclusion Dietary education that is sensitive to the attitudes, wishes, and preferences of the participants and that aims at establishing a connection to the everyday life of the participants might facilitate successful changes in dietary practices among people with a Pakistani background and type 2 diabetes. The findings suggest that more focus should be placed on collaborative processes in the dietary educational setting in order to achieve appropriate education and to improve communication between this population and health care professionals. PMID:25750523

  14. Scholars' Satisfaction with Digital Library Collection and Gaps in the Provision of Effective Information Resources and Services: A Pakistani Perspective

    ERIC Educational Resources Information Center

    Khan, Amjid; Ahmed, Shamshad; Masrek, Mohamad Noorman

    2014-01-01

    The study aims to explore the researchers' satisfaction with digital library resources and services and how they improved the research culture in Pakistani universities. A descriptive survey method was employed to achieve objectives of this study. Using stratified random sampling, for this survey we selected 14 public sector universities of…

  15. Parenting and Infant Temperament amongst Pakistani Women Living in the UK According to Country of Birth: Results from the Born in Bradford Cohort Study

    ERIC Educational Resources Information Center

    Prady, Stephanie L.; Kiernan, Kathleen; Fairley, Lesley; Wright, John

    2013-01-01

    Some parenting behaviours and child characteristics can result in future behavioural problems. Relatively little is known about parenting behaviours in Pakistani-origin women, and how the timing of migration to the United Kingdom might affect such behaviours. We analysed differences in parenting behaviours and six-month infant temperament by…

  16. Adjustable recessions in horizontal comitant strabismus: A pilot study

    PubMed Central

    Agrawal, Siddharth; Singh, Vinita; Singh, Priyanka

    2015-01-01

    Aim: To compare the surgical outcome of adjustable with the conventional recession in patients with horizontal comitant strabismus. Patients and Methods: A prospective comparative nonrandomized interventional pilot study was performed on patients with horizontal comitant strabismus. Fifty-four patients (27 in each group) were allocated into 2 groups to undergo either adjustable suture (AS) recession or non-AS (NAS) recession along with conventional resection. The patients were followed up for 6 months. A successful outcome was defined as deviation ±10 prism diopters at 6 months. The results were statistically analyzed by Chi-square test, Fisher's exact test, and Student's t-test. Results: A successful outcome was found in 24 (88.8%) patients in AS and 17 (62.9%) in NAS group (P = 0.02). The postoperative adjustment was done in 13 (48.1%) patients in AS group. There was one complication (tenon's cyst) in AS group. Conclusion: AS recession may be considered in all cooperative patients undergoing strabismus surgery for comitant deviations. PMID:26458480

  17. 13. DETAIL VIEW, OF TAINTER GATE PIER, SHOWING RECESSES FOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. DETAIL VIEW, OF TAINTER GATE PIER, SHOWING RECESSES FOR EMERGENCY BULKHEADS AND DOGGING DEVICES, LOOKING SOUTHEAST (DOWN FACE). UPSTREAM FACE OF TAINTER GATE IS VISIBLE IN UPPER RIGHT CORNER - Upper Mississippi River 9-Foot Channel Project, Lock & Dam 26R, Alton, Madison County, IL

  18. Applications to One Business School Skyrocketed Despite Recession

    ERIC Educational Resources Information Center

    Tao, Sharon

    2010-01-01

    In the past two years, the global financial crisis has wreaked havoc on businesses in America and abroad. But the gloom and doom seems to have had the opposite effect on business schools. The reason is that a recession often signals the perfect time for proactive students to sharpen their skill sets, shift their career goals (whether toward a…

  19. Recess, Physical Education, and Elementary School Student Outcomes

    ERIC Educational Resources Information Center

    Dills, Angela K.; Morgan, Hillary N.; Rotthoff, Kurt W.

    2011-01-01

    Today's children experience a decreased amount of time at recess and fewer physical education (PE) classes throughout the school day. Breaks for physical activity limit class time for academics, potentially reducing learning. However, breaks may improve alertness and achievement. Using the Early Childhood Longitudinal Survey Kindergarten Class of…

  20. Recession Amnesia and the Prospects for New England's Institutions

    ERIC Educational Resources Information Center

    Halfond, Jay A.

    2010-01-01

    Among the little truly predictable, the author suggests three truths. First is the inevitability of recessions. Second is the belief that, in prosperity, these good times will just keep on rolling. Third is the fall. Bubbles will burst, myths shatter, plans unravel and pain sadly borne unjustly by those who didn't have a hand in the decisions that…

  1. 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. PMID:26494409

  2. Reporting of haplotypes with recessive effects on fertility

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genomic discovery of five haplotypes with recessive effects on fertility requires new automated tracking methods for QTL causing embryo loss in breeding programs. Most of the losses are early in gestation. Approximate locations of the five QTL were refined using crossovers detected within the pedigr...

  3. Following the Cuts: How Is the Recession Affecting Faculty Work?

    ERIC Educational Resources Information Center

    Lounder, Andrew; Waugaman, Chelsea; Kenyon, Mark; Levine, Amy; Meekins, Matthew; O'Meara, KerryAnn

    2011-01-01

    The recession of 2008-2009 and the continuing decline in local, state, and federal funds available to support higher education have resulted in serious budget cuts and belt-tightening. Given that faculty constitute an institution's most costly resource, it was not surprising, though it is nonetheless disheartening, to learn of the University of…

  4. Intrinsically Motivated, Free-Time Physical Activity: Considerations for Recess

    ERIC Educational Resources Information Center

    Stellino, Megan Babkes; Sinclair, Christina D.

    2008-01-01

    The current childhood obesity rates raise concern about youths' health and the role that a sedentary lifestyle plays in this growing trend. Focusing on how children choose to spend their free time is one approach that may yield ideas for reducing childhood obesity. Recess is a regularly occurring "free time" period in elementary schools. It is,…

  5. 15. INTERIOR OF DINING ROOM SHOWING RECESSED TELEPHONE ALCOVE IN ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    15. INTERIOR OF DINING ROOM SHOWING RECESSED TELEPHONE ALCOVE IN PARTION WALL BETWEEN LIVING ROOM AND DINING ROOM AT PHOTO RIGHT CENTER. OPEN DOOR AT PHOTO LEFT CENTER LEADS TO BEDROOM NO.2. VIEW TO NORTH. - Bishop Creek Hydroelectric System, Plant 4, Worker Cottage, Bishop Creek, Bishop, Inyo County, CA

  6. Unemployment of Family Breadwinners: The Recession of 1975.

    ERIC Educational Resources Information Center

    Moen, Phyllis

    Using 1975 and 1976 data from the Michigan Panel Study of Income Dynamics, this study examines the significance of the 1975 recession for families with children under 18. This study attempted to ascertain what families with children were most susceptible to having an unemployed breadwinner in 1975 and why some family heads were more susceptible to…

  7. 3. EXTERIOR OF FRONT ENTRY SHOWING GABLE OVER RECESSED PORCH ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. EXTERIOR OF FRONT ENTRY SHOWING GABLE OVER RECESSED PORCH WITH RUSTIC STYLE DECORATIVE TREATMENT. WELDED STEEL PORCH RAILING ADDED IN 1972 IS VISIBLE AT PHOTO CENTER. VIEW TO SOUTHWEST. - Rush Creek Hydroelectric System, Worker Cottage, Rush Creek, June Lake, Mono County, CA

  8. 10. VIEW EAST, RECESS AREA WITH BOTTOM HORIZONTAL BEAM FOR ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    10. VIEW EAST, RECESS AREA WITH BOTTOM HORIZONTAL BEAM FOR EAST GATE - Bald Eagle Cross-Cut Canal Lock, North of Water Street along West Branch of Susquehanna River South bank, 500 feet East of Jay Street Bridge, Lock Haven, Clinton County, PA

  9. 11. VIEW WEST, RECESS AREA WITH PORTION OF MITER SILL ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    11. VIEW WEST, RECESS AREA WITH PORTION OF MITER SILL (Numbers painted on stones for reconstruction purposes) - Bald Eagle Cross-Cut Canal Lock, North of Water Street along West Branch of Susquehanna River South bank, 500 feet East of Jay Street Bridge, Lock Haven, Clinton County, PA

  10. 12. VIEW WEST, AREA SOUTH OF RECESS AREA, SHOWING CUT ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    12. VIEW WEST, AREA SOUTH OF RECESS AREA, SHOWING CUT STONE AND RUBBLESTONE CONSTRUCTION - Bald Eagle Cross-Cut Canal Lock, North of Water Street along West Branch of Susquehanna River South bank, 500 feet East of Jay Street Bridge, Lock Haven, Clinton County, PA

  11. Employment of Ex-Offenders during the Recession

    ERIC Educational Resources Information Center

    Nally, John M.; Lockwood, Susan R.; Ho, Taiping

    2011-01-01

    Researchers have rarely examined post-release employment among offenders during a period of economic recession. However, studies on employment issues among post-release offenders have showed that released offenders would likely have a higher unemployment rate due to their inadequate education and job skills (Batiuk, 1997; Harlow, 2003; Vacca,…

  12. 17. Emplacement no. 1, showing (LR): recess for powder hoist, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    17. Emplacement no. 1, showing (L-R): recess for powder hoist, truncated remains of reserve table for projectile, teleautograph niche, and steps to crest of parapet - Fort Wadsworth Battery Romeyn B. Ayers, South side of Ayers Road, Staten Island, Rosebank, Richmond County, NY

  13. Hard Times. The Recession Imperils School Reforms and Teachers' Jobs.

    ERIC Educational Resources Information Center

    Harp, Lonnie

    1991-01-01

    The current recession in the United States imperils teachers' jobs and school reform. States are prioritizing increased spending in such areas as health care and transportation rather than educational improvement. The article discusses specific educational hard times in several states and counties. (SM)

  14. Tag, Catch, and Other Unnatural Acts at Recess (Circa 2014)

    ERIC Educational Resources Information Center

    Sydnor, Synthia

    2014-01-01

    This commentary details a news event in which Carrie Weber Middle School in Port Washington, NY, supposedly banned students from using balls, playing tag, and doing cartwheels during recess. Public reaction in the form of news items, tweets, blogs, and commentary is sampled, and news releases from the Weber Middle School that were barely covered…

  15. 14. DETAIL: Gate recess at east gate area. Planking of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    14. DETAIL: Gate recess at east gate area. Planking of chamber walls and spikes (rear corner) are clearly visible. - Wabash & Erie Canal, Lock No. 2, 8 miles east of Fort Wayne, adjacent to U.S. Route 24, New Haven, Allen County, IN

  16. 57. View looking west. Detail of a recess cut into ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    57. View looking west. Detail of a recess cut into the southwest corner of the forebay crib floor decking. This aperture was made to receive the crib buttress. - Wabash & Erie Canal, Lock No. 2, 8 miles east of Fort Wayne, adjacent to U.S. Route 24, New Haven, Allen County, IN

  17. Young School Children's Recess Physical Activity: Movement Patterns and Preferences

    ERIC Educational Resources Information Center

    Woods, Amelia M.; Graber, Kim C.; Daum, David N.; Gentry, Chris

    2015-01-01

    This study examined physical activity (PA) variables related to recess PA patterns of kindergarten, first and second grade children, and the social preferences and individuals influencing their PA. Data collected (N = 147) used the System of Observing Children's Activity and Relationships during Play (SOCARP) instrument. Children were interviewed.…

  18. 1. VIEW LOOKING EAST AT LOWER GATE RECESS AND LOWER ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. VIEW LOOKING EAST AT LOWER GATE RECESS AND LOWER GUIDE WALL FROM THE OHIO RIVER. - Ohio Slack Water Dams, Lock & Dam No. 4, East bank of Ohio River at mile point 18.6, along State Route 65, Ambridge, Beaver County, PA

  19. 3. VIEW LOOKING EAST AT UPPER GATE RECESS FROM THE ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    3. VIEW LOOKING EAST AT UPPER GATE RECESS FROM THE OHIO RIVER. (NOTE: REMAINS OF TRACKS FROM ROLLING LOCK GATE, PARTIALLY SUBMERGED.) - Ohio Slack Water Dams, Lock & Dam No. 4, East bank of Ohio River at mile point 18.6, along State Route 65, Ambridge, Beaver County, PA

  20. The Effects of Inflation/Recession on Higher Education.

    ERIC Educational Resources Information Center

    Bowen, William G.

    This document discusses the effects of inflation on colleges and universities. It attempts to explain the basic nature of the current financial problem so that more informed policy decisions can be made. The document discusses the effect of inflation on costs and the effects of inflation/recession on revenues. Chart 1 indicated the Halstead Higher…

  1. Coping with Recession: Public Policy, Economic Downturns and Higher Education.

    ERIC Educational Resources Information Center

    Callan, Patrick M.

    This paper discusses recession and the major policy considerations that states and institutions must face in the current economic downturn. It explores the public policy implications of three major variables: (1) each of the 50 states has a unique higher education system; (2) each state also has a unique revenue and budgetary process; and (3) each…

  2. Increasing Physical Activity of Children during School Recess

    ERIC Educational Resources Information Center

    Hayes, Lynda B.; Van Camp, Carole M.

    2015-01-01

    Physical activity is crucial for children's health. Fitbit accelerometers were used to measure steps of 6 elementary students during recess. The intervention included reinforcement, self-monitoring, goal setting, and feedback. Steps taken during the intervention phase (M?=?1,956 steps) were 47% higher than in baseline (M?=?1,326 steps), and the…

  3. The Post-Recession Employment Situation: A Comparative Perspective

    ERIC Educational Resources Information Center

    Couch, Kenneth A.

    2012-01-01

    Slow economic growth since the end of the U.S. recession in June of 2009 has not yet translated into increases in employment large enough to meaningfully reduce the rate of unemployment. Because expansionary macroeconomic policy has been pursued on both the fiscal and monetary fronts, it appears at first glance that the hands of government at this…

  4. Surgical correction of gingival recessions associated with radicular carious lesions.

    PubMed

    Urbani, G; Lombardo, G; Castellarin, M; Santi, E; Abitbol, T

    1996-04-01

    In this clinical report, six cases are presented in which radicular carious lesions and gingival recessions were treated concurrently. The combined treatment included the removal of caries, radicular planing, and various surgical techniques for root coverage. Traditional procedures, as well as newer procedures, such as guided tissue regeneration, showed successful results. PMID:9051969

  5. College Costs, Prices and the Great Recession. Lumina Issue Papers

    ERIC Educational Resources Information Center

    Johnson, Nate

    2014-01-01

    As states and families begin to recover from the effects of the Great Recession, some of the urgency about college affordability may start to ease. The most recent "Trends in College Pricing" report shows tuition rising more slowly than in recent years (Baum and Ma 2013). Growth in Pell grant applications is also expected to slow as…

  6. Economic recession and fertility in the developed world.

    PubMed

    Sobotka, Tomáš; Skirbekk, Vegard; Philipov, Dimiter

    2011-01-01

    This article reviews research on the effects of economic recessions on fertility in the developed world. We study how economic downturns, as measured by various indicators, especially by declining GDP levels, falling consumer confidence, and rising unemployment, were found to affect fertility. We also discuss particular mechanisms through which the recession may have influenced fertility behavior, including the effects of economic uncertainty, falling income, changes in the housing market, and rising enrollment in higher education, and also factors that influence fertility indirectly such as declining marriage rates. Most studies find that fertility tends to be pro-cyclical and often rises and declines with the ups and downs of the business cycle. Usually, these aggregate effects are relatively small (typically, a few percentage points) and of short durations; in addition they often influence especially the timing of childbearing and in most cases do not leave an imprint on cohort fertility levels. Therefore, major long-term fertility shifts often continue seemingly uninterrupted during the recession—including the fertility declines before and during the Great Depression of the 1930s and before and during the oil shock crises of the 1970s. Changes in the opportunity costs of childbearing and fertility behavior during economic downturn vary by sex, age, social status, and number of children; childless young adults are usually most affected. Furthermore, various policies and institutions may modify or even reverse the relationship between recessions and fertility. The first evidence pertaining to the recent recession falls in line with these findings. In most countries, the recession has brought a decline in the number of births and fertility rates, often marking a sharp halt to the previous decade of rising fertility rates. PMID:22066128

  7. 46 CFR 171.067 - Treatment of stepped and recessed bulkheads in Type I subdivision.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... and the transverse plane passing through the nearest portion of a recessed bulkhead must be greater... recessed, equivalent plane bulkheads must be used in the calculations required to demonstrate...

  8. Association of Body Iron Status with the Risk of Premature Acute Myocardial Infarction in a Pakistani Population

    PubMed Central

    Iqbal, Mohammad Perwaiz; Mehboobali, Naseema; Tareen, Asal Khan; Yakub, Mohsin; Iqbal, Saleem Perwaiz; Iqbal, Khalida; Haider, Ghulam

    2013-01-01

    Background Coronary artery disease is very common in Pakistani population. Some of the studies carried out on Western populations have shown a relationship between body iron status as determined by the ratio of concentrations of serum soluble transferrin receptor (sTfR) to ferritin and the risk of acute myocardial infarction (AMI). In order to investigate whether increased body iron status has any relationship with the risk of premature AMI in Pakistani population, a case-control study was carried out. Methodology/Principal findings In this case-control study, 203 consecutive AMI patients [146 males and 57 females; age range 18–45 years] admitted to the National Institute for Cardiovascular Diseases, Karachi, were enrolled with informed consent. In addition, 205 healthy controls whose gender and age (within 3 years) matched the patients, and who had a similar socio-economic background were recruited. Fasting venous blood was obtained and assessed for plasma/serum folate, vitamin B12, homocysteine, total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, sTfR and ferritin and blood lead. It was found that serum concentration of ferritin and blood lead levels were significantly higher in AMI patients compared to their age and gender-matched healthy controls (p value <0.05), while the concentrations of vitamin B12 and HDL-cholesterol were significantly lower in AMI patients compared to controls (p value <0.01). The ratio of sTfR to ferritin was significantly lower in AMI patients compared to controls [mean±SD/median (IQR) values 84.7±295/28.9 (38.4) vs 255±836/49.4 (83.8), respectively; p value <0.001]. Compared with the highest quartile of sTfR/ferritin (low body iron status), the OR for the risk of AMI was 3.29(95% CI, 1.54–7.03) for the lowest quartile (quartile 1) when the model was adjusted for vitamin B12 and HDL-cholesterol (p value for trend <0.01). Conclusions/Significance This study shows a positive association between total body iron

  9. Did Cuts in State Aid during the Great Recession Lead to Changes in Local Property Taxes?

    ERIC Educational Resources Information Center

    Chakrabarti, Rajashri; Livingston, Max; Roy, Joydeep

    2014-01-01

    The Great Recession led to marked declines in state revenue. In this paper we investigate whether (and how) local school districts modified their funding and taxing decisions in response to state aid declines in the post-recession period. Our results reveal school districts responded to state aid cuts in the post-recession period by countering…

  10. Proposed Strategy for Selection Against Recessive Genetic Defects Through a Combination of Inbreeding and DNA Markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recessive genetic defects are currently on the minds of many cattle breeders. The relatively rapid development of diagnostic DNA tests for recessive defects appears to be a major recent technological advancement. However, the attitude of breeders and breed associations toward recessive defects seems...

  11. Elementary School Recess: Selected Readings, Games, and Activities for Teachers and Parents.

    ERIC Educational Resources Information Center

    Clements, Rhonda L., Ed.

    Based upon the principle that all children have a right to play and to experience the benefits of recess, this book assists elementary school teachers and parents in offering children in preschool through Grade 6 appropriate recess games and activities and provides a variety of readings that support the need for recess activities. The book is…

  12. Recess and Reading Achievement of Early Childhood Students in Public Schools

    ERIC Educational Resources Information Center

    Yesil Dagli, Ummuhan

    2012-01-01

    In recent years, schools have tended to eliminate recess period and to devote more time to instruction in order to increase academic achievement. Using a nationally representative sample, this study examined reading scores of students who experienced different numbers of recess days in a week, and different number of times and length of recess in…

  13. Ready for Recess: A Pilot Study to Increase Physical Activity in Elementary School Children

    ERIC Educational Resources Information Center

    Huberty, Jennifer L.; Siahpush, Mohammad; Beighle, Aaron; Fuhrmeister, Erin; Silva, Pedro; Welk, Greg

    2011-01-01

    Background: Creating an optimal environment at recess may be necessary to maximize physical activity (PA) participation in youth. The purpose of this study was to determine the initial effectiveness of an elementary school recess intervention on the amount of moderate PA (MPA) and vigorous PA (VPA) during recess and the school day. Methods: This…

  14. Non-Overweight and Overweight Children's Physical Activity during School Recess

    ERIC Educational Resources Information Center

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

    2014-01-01

    Objective: Little research has investigated children's physical activity levels during school recess and the contribution of recess to school day physical activity levels by weight status. The aims of this study were to examine non-overweight and overweight children's physical activity levels during school recess, and examine the…

  15. Give Me a Break! Can Strategic Recess Scheduling Increase On-Task Behaviour for First Graders?

    ERIC Educational Resources Information Center

    Fagerstrom, Todd; Mahoney, Kate

    2006-01-01

    The purpose of this study was to determine whether strategically scheduled recess breaks throughout the school day will increase student on-task behaviours during the time when students work independently. As an intervention for this action research study, recess breaks were given more often but for less time; recess breaks were scheduled before…

  16. Effect of succinylation on functional and morphological properties of starches from broken kernels of Pakistani Basmati and Irri rice cultivars.

    PubMed

    Moin, Abeera; Ali, Tahira Mohsin; Hasnain, Abid

    2016-01-15

    Starch extracted from broken kernels of Basmati and Irri rice varieties of Pakistani rice were subjected to modification by addition of succinic anhydride at levels of 2%, 4% and 5% based on dried weight of starch. The succinyl content of Irri rice starch increased with the concentration of succinic anhydride. Scanning electron micrographs revealed presence of dents and fusion of rice starch granules. Swelling power and water retention capacity (WRC) significantly improved after succinylation while on refrigerated storage percent decline in paste clarity of modified rice starches was stable as compared to native Basmati (BC) and Irri (IC) rice starches. Succinylation also reduced solubility, pasting temperature (PT) and gel hardness of starch gels. Improvement was observed in cold storage stability of rice starch succinates as evident from textural profile analysis. PMID:26258701

  17. Short Communication: Lack of association between MTHFR gene polymorphisms and response to methotrexate treatment in Pakistani patients with rheumatoid arthritis.

    PubMed

    Iqbal, Mohammad Perwaiz; Ali, Azra Arif; Mehboobali, Naseema; Iqbal, Khalida

    2015-09-01

    Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with response to methotrexate (MTX) in certain populations of patients with rheumatoid arthritis (RA). This study aims at investigating any relationship of two single nucleotide polymorphisms (SNPs) in MTHFR gene, C677T and A1298C with response to therapy with MTX in Pakistani RA patients. Allelic frequencies of the two polymorphisms (C677T and A1298C) were determined in 67 RA patients (9 males and 58 females; mean age 42.87 ± 13.5 years) who had previously participated in a prospective clinical trial. Fifty-one patients had received MTX and were followed up for response up to 6 months. Genotyping of the two MTHFR polymorphisms was carried out using PCR-RFLP, while fasting concentration of plasma homocysteine was determined using a kit method. Twenty-eight patients were found to be "good responders", while twenty-three were "poor responders". MTHFR 1298C and MTHFR 677T alleles' frequencies in "good responders" were not different from frequencies in "poor responders" (0.574 vs. 0.521; p=0.6 and 0.197 vs. 0.196; p=0.75, respectively). Plasma homocysteine levels in female RA patients were significantly higher compared to general population in Karachi (13.1 ± 6.7 µmol/l vs. 11.4 ± 5.3 µmol/l; p<0.001). MTHFR C677T and A1298C polymorphisms are not associated with response to MTX in a population of Pakistani RA patients. PMID:26408898

  18. Effect of six type II diabetes susceptibility loci and an FTO variant on obesity in Pakistani subjects.

    PubMed

    Shabana; Ullah Shahid, Saleem; Wah Li, Ka; Acharya, Jayshree; Cooper, Jackie A; Hasnain, Shahida; Humphries, Stephen E

    2016-06-01

    The aim of the current study was to analyze the effect of six type II diabetes GWAS loci rs3923113 (GRB14), rs16861329 (ST6GAL1), rs1802295 (VPS26A), rs7178572 (HMG20A), rs2028299 (AP3S2) and rs4812829 (HNF4A), and an FTO polymorphism (rs9939609) on obesity. The probable mechanism of action of these SNPs was analyzed by studying their association with various biochemical and anthropometric parameters. A total of 475 subjects (obese=250, controls=225) were genotyped by TaqMan assay and their lipid profile was determined. Allele/genotype frequencies and an unweighted/weighted gene score were calculated. The effect of the gene score on anthropometric and biochemical parameters was analyzed. The minor allele frequencies of all variants were comparable to that reported in the original studies and were associated with obesity in these Pakistani subjects. Subjects with 9 risk alleles differ from those with <3 and overall there is no significant effect (P-value for trend 0.26). None of the SNPs were associated with any of the serum lipid traits. We are the first to report the association of these T2D SNPs with obesity. In the Pakistani population the reported effect of six SNPs for obesity is similar to that reported for T2D and having a combination of risk alleles on obesity can be considerable. The mechanism of this effect is unclear, but appears not to be mediated by changing serum lipid chemistry. PMID:26395551

  19. Caroli's syndrome with autosomal recessive polycystic kidney disease.

    PubMed

    Shenoy, Prithi; Zaki, Syed Ahmed; Shanbag, Preeti; Bhongade, Swapnil

    2014-07-01

    Caroli's syndrome (CS) is a rare congenital disorder characterized by multiple segmental cystic or saccular dilatations of the intrahepatic bile ducts and congenital hepatic fibrosis. We report a 9-year-old boy who was diagnosed with CS and autosomal recessive poly-cystic kidney disease. On screening, his 5-month-old asymptomatic sister had multiple dilated biliary radicals with multiple bilateral renal cystic lesions. Both the patient and the affected sibling have been advised regular follow-up for monitoring the progression of the disease. In conclusion, patients with CS should be screened for renal cystic lesions and vice versa even if they are asymptomatic. Also, as the disease is inherited in an autosomal recessive manner, it is important to screen family members for early diagnosis and management. PMID:24969198

  20. The Great Recession, Public Transfers, and Material Hardship

    PubMed Central

    Pilkauskas, Natasha V.; Currie, Janet; Garfinkel, Irwin

    2013-01-01

    Economic downturns lead to lost income and increased poverty. Although high unemployment almost certainly also increases material hardship, and government transfers likely decrease hardship, the first relationship has not yet been documented and the second is poorly understood. We use data from five waves of the Fragile Families and Child Well-being Study to study the relationships between unemployment, government transfers, and material hardship. The latest wave of data was collected during the Great Recession, the worst recession since the Great Depression, providing a unique opportunity to look at how high unemployment rates affect the well-being of low income families. We find that the unemployment rate is associated with increased overall material hardship, difficulty paying bills, having utilities disconnected, and with increased usage of TANF, SNAP, UI and Medicaid. If not for SNAP, food hardship might have increased by twice the amount actually observed. PMID:24379487