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1

Clinical Polymorphism of Stargardt Disease in a Large Consanguineous Tunisian Family; Implications for Nosology  

PubMed Central

Purpose To describe the polymorphic expression of Stargardt disease in a large Tunisian family with clinical intra- and interfamilial variation of the condition. Methods Twelve subjects from two related families with autosomal recessive Stargardt disease were enrolled. A detailed clinical examination including visual acuity and visual field measurement, fundus photography, fluorescein angiography, electroretinography (ERG) and color vision testing was performed for all subjects. Results The youngest child from family A manifested typical Stargardt disease while her two brothers presented with Stargardt disease-fundus flavimaculatus (STGD-FFM) and her two sisters demonstrated a peculiar phenotype overlapping Stargardt disease and cone-rod dystrophy; their phenotypic manifestation corresponded well with ERG groups I, II and III, respectively. This uncommon occurrence of an age-related decline in ERG amplitude and worsening of fundus changes is suggestive of a grading pattern in Stargardt disease. Their two cousins in family B, displayed the STGD-FFM phenotype. Despite clinically similar STGD-FFM patterns in both families, age of onset and progression of the phenotype in family B differed from family A. Conclusion This is the first report on phenotypic variation of Stargardt disease in a large Tunisian family. Regarding phenotype and severity of visual symptoms, family A demonstrated Stargardt disease at various stages of progression. In addition, STGD-FFM appeared to be an independent clinical entity in family B. These findings imply that further parameters are required to classify Stargardt’s disease. PMID:24653822

El Matri, Leila; Ouechtati, Farah; Chebil, Ahmed; Largueche, Leila; Abdelhak, Sonia

2013-01-01

2

Nonprogressive autosomal recessive ataxia maps to chromosome 9q34-9qter in a large consanguineous Lebanese family.  

PubMed

Congenital ataxias are a heterogeneous group of predominantly nonprogressive disorders characterized by hypotonia, developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We performed a genome-wide screen on a large inbred Lebanese family presenting a nonprogressive autosomal recessive congenital cerebellar ataxia associated with short stature (MIM 213200), already described by Mégarbané and colleagues. The disease locus was assigned to a 12.1 cM interval on chromosome 9q34-9qter between D9S67 and D9S312. Differential diagnosis with other hereditary ataxias linked to the same region is discussed. PMID:11506409

Delague, V; Bareil, C; Bouvagnet, P; Salem, N; Chouery, E; Loiselet, J; Mégarbané, A; Claustres, M

2001-08-01

3

Linkage Analysis in a Large Family from Pakistan with Depression and a High Incidence of Consanguineous Marriages  

Microsoft Academic Search

Objectives: A genome wide scan for linkage was performed in a five generation family with a high incidence of depression and high average coefficient of inbreeding ascertained in a rural area of Pakistan. The effect of inbreeding on linkage analysis in an extended pedigree is discussed. Methods: 372 microsatellite markers were used in a genome wide linkage study. Inbreeding coefficients

Muhammad Ayub; Muhammad Irfan; Alan Maclean; Farooq Naeem; Stuart MacGregor; Peter M. Visscher; Walter Muir; Douglas Blackwood

2008-01-01

4

A novel mutation in GRK1 causes Oguchi disease in a consanguineous Pakistani family  

Microsoft Academic Search

Purpose: The purpose of this study was to identify the underlying molecular genetic defect in a large consanguineous Pakistani family with Oguchi disease who had been given a diagnosis of autosomal recessive retinitis pigmentosa. Methods: The family was genotyped with the Affymetrix 10K single nucleotide polymorphism array. Fine-mapping of a common homozygous region on chromosome 13q was performed using fluorescent

Maleeha Azam; Rob W. J. Collin; Muhammad Imran Khan; S. T. Shah; N. Qureshi; M. Ajmal; A. I. den Hollander; R. Qamar; F. P. M. Cremers

2009-01-01

5

A consanguineous family with Hirschsprung disease, microcephaly, and mental retardation (Goldberg-Shprintzen syndrome)  

Microsoft Academic Search

Hirschsprung disease, mental retardation, microcephaly, and specific craniofacial dysmorphism were observed in three children from a large, consanguineous, Moroccan family. A fourth child showed similar clinical features, with the exception of Hirschsprung disease. The association of these abnormalities in these children represents the Goldberg-Shprintzen syndrome (OMIM 235730). Mutation scanning of genes potentially involved in Hirschsprung disease, RET, GDNF, EDN3, and

Alice S Brooks; Martijn H Breuning; Jan Osinga; Jasper J vd Smagt; Corine E Catsman; Charles H C M Buys; Carel Meijers; Robert M W Hofstra

1999-01-01

6

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

PubMed

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

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

7

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

PubMed

Mirror movements (MRMV) are involuntary movements on one side of the body that mirror voluntary movements on the opposite side. Congenital mirror movement disorder is a rare, typically autosomal-dominant disorder, although it has been suspected that some sporadic cases may be due to recessive inheritance. Using a linkage analysis and a candidate gene approach, two genes have been implicated in congenital MRMV disorder to date: DCC on 18q21.2 (MRMV1), which encodes a netrin receptor, and RAD51 on 15q15.1 (MRMV2), which is involved in the maintenance of genomic integrity. Here, we describe a large consanguineous Pakistani family with 11 cases of congenital MRMV disorder reported across five generations, with autosomal recessive inheritance likely. Sanger sequencing of DCC and RAD51 did not identify a mutation. We then employed microarray genotyping and autozygosity mapping to identify a shared region of homozygosity-by-descent among the affected individuals. We identified a large autozygous region of ~3.3 Mb on chromosome 22q13.1 (Chr22:36605976-39904648). We used Sanger sequencing to exclude several candidate genes within this region, including DMC1 and NPTXR. Whole exome sequencing was employed, and identified a splice site mutation in the dynein axonemal light chain 4 gene, DNAL4. This splice site change leads to skipping of exon 3, and omission of 28 amino acids from DNAL4 protein. Linkage analysis using Simwalk2 gives a maximum Lod score of 6.197 at this locus. Whether or how DNAL4 function may relate to the function of DCC or RAD51 is not known. Also, there is no suggestion of primary ciliary dyskinesis, situs inversus, or defective sperm in affected family members, which might be anticipated given a putative role for DNAL4 in axonemal-based dynein complexes. We suggest that DNAL4 plays a role in the cytoplasmic dynein complex for netrin-1-directed retrograde transport, and in commissural neurons of the corpus callosum in particular. This, in turn, could lead to faulty cross-brain wiring, resulting in MRMV. PMID:25098561

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

2014-11-01

8

Five new consanguineous families with horizontal gaze palsy and progressive scoliosis and novel ROBO3 mutations  

Microsoft Academic Search

Horizontal gaze palsy and progressive scoliosis (HGPPS) is an autosomal recessive neurologic disorder caused by homozygous or compound heterozygous mutations in the ROBO3 gene on chromosome 11. We clinically evaluated seven individuals with HGPPS from five previously unreported consanguineous families. We sequenced ROBO3 in all affected individuals, additional unaffected members of each family, and ethnic controls. All affected individuals had

Khaled K. Abu-Amero; Hesham al Dhalaan; Zayed al Zayed; Ali Hellani; Thomas M. Bosley

2009-01-01

9

Novel SIL1 mutations in consanguineous Pakistani families mapping to chromosomes 5q31  

PubMed Central

Purpose To investigate the genetic basis of Marinesco-Sjogren syndrome (MSS) in consanguineous Pakistani families. Methods Two consanguineous Pakistani families with congenital cataract and muscular dystrophy were enrolled for this study. Detailed ophthalmic and systemic examination including slit lamp microscopy, electromyogram and computed tomography scans were performed to characterize the syndrome. Blood samples were collected from affected and unaffected individuals and a genome wide scan consisting of 382 polymorphic microsatellite markers was performed. Coding exons, exon-intron boundaries, 5’ UTR, and 3’ UTR of the candidate gene SIL1 residing in the linkage interval was sequenced bi-directionally. Results Clinical examination of the affected members of families 60067 and 60078 revealed features of MSS. The linked interval at chromosome 5q31 harbors SIL1. Sequencing of SIL1 in family 60067 revealed a homozygous substitution; c1240C>T, leading to a premature substitution; p.Q414X. Similarly, sequencing of SIL1 in family 60078 identified a homozygous change; c.274C>T, leading to a non conservative substitution; p.R92W. Conclusion In conclusion, our data report two novel missense mutations in two consanguineous Pakistani families affected with MSS. PMID:19471582

Amiri-Kordestani, Laleh; Kaul, Haiba; Butt, Tariq; Jiao, Xiaodong; Riazuddin, Sheikh; Hejtmancik, J. Fielding

2009-01-01

10

Clinical evaluation of two consanguineous families with homozygous mutations in BEST1  

PubMed Central

Purpose To describe the clinical and genetic findings in two consanguineous families with Best vitelliform macular dystrophy (BVMD) and homozygous mutations in the bestrophin-1 (BEST1) gene. Methods Ophthalmologic examination was performed in eight members of two families originating from Spain and Denmark. Mutation screening was performed using the Vitelliform Macular Dystrophy mutation array from Asper Biotech, and by the directed genomic sequencing of BEST1. Results Two homozygous mutations were detected in these families. Mutation c.936C>A (p.Asp312Glu) has been reported previously in a Danish family; here, we describe four additional individuals in this family demonstrating findings compatible with a severe dominant BVMD, albeit with reduced penetrance in heterozygotes. In the Spanish family, a novel homozygous missense mutation in exon 4, c.388 C>A (p.Arg130Ser), was identified in the siblings. Homozygous siblings demonstrated evidence of multifocal vitelliform retinopathy, whereas heterozygous family members presented findings ranging from isolated reduction of the electrooculogram Arden ratio to normal values on all clinical parameters. Conclusions As demonstrated in these consanguineous families, a great clinical variability is associated with homozygous mutations in BEST1, ranging from severe dominant BVMD with reduced penetrance in heterozygotes to autosomal recessive bestrophinopathy. PMID:21738390

Pineiro-Gallego, Teresa; Alvarez, Maria; Pereiro, Ines; Campos, Severiano; Sharon, Dror; Schatz, Patrik

2011-01-01

11

Studies in a consanguineous family reveal a novel locus for stuttering on chromosome 16q  

PubMed Central

Stuttering is a common neurologic disorder in children that can persist into adulthood. Although stuttering displays high heritability, Mendelian segregation typically does not occur, and linkage studies have produced limited success. A genome-wide single nucleotide polymorphism (SNP) linkage scan in a consanguineous Pakistani family followed by targeting genotyping using microsatellite markers revealed linkage on chromosome 16q. The highest linkage scores were obtained under a modified recessive model of inheritance, with a maximum multipoint LOD score of 4.42 at marker D16S3043. PMID:22205390

Raza, M. Hashim; Ali, Rana Amjad; Riazuddin, S.; Drayna, Dennis

2012-01-01

12

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

PubMed

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

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

13

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

Microsoft Academic Search

.   Congenital cerebellar ataxias are a heterogeneous group of non-progressive disorders characterized by hypotonia and developmental\\u000a delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum.\\u000a We report the mapping of a disease gene in a large inbred Lebanese Druze family, with five cases of a new form of non-progressive\\u000a autosomal

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

2002-01-01

14

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

PubMed

Congenital cerebellar ataxias are a heterogeneous group of non-progressive disorders characterized by hypotonia and developmental delay followed by the appearance of ataxia, and often associated with dysarthria, mental retardation, and atrophy of the cerebellum. We report the mapping of a disease gene in a large inbred Lebanese Druze family, with five cases of a new form of non-progressive autosomal recessive congenital ataxia associated with optic atrophy, severe mental retardation, and structural skin abnormalities, to a 3.6-cM interval on chromosome 15q24-15q26. PMID:12030328

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

2002-03-01

15

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

PubMed Central

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.

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

2014-01-01

16

Homozygosity mapping in 64 Syrian consanguineous families with non-specific intellectual disability reveals 11 novel loci and high heterogeneity  

PubMed Central

Non-specific intellectual disability of autosomal recessive inheritance (NS-ARID) represents an important fraction of severe cognitive dysfunction disorders. To date, only 10 genes have been identified, and further 24 linked-ARID loci have been reported, as well as others with suggestive linkage. To discover novel genes causing NS-ARID, we undertook genome-wide homozygosity mapping in 64 consanguineous multiplex families of Syrian descent. A total of 11 families revealed unique, significantly linked loci at 4q26-4q28 (MRT17), 6q12-q15 (MRT18), 18p11 (MRT19), 16p12-q12 (MRT20), 11p15 (MRT21), 11p13-q14 (MRT23), 6p12 (MRT24), 12q13-q15 (MRT25), 14q11-q12 (MRT26), 15q23-q26 (MRT27), and 6q26-q27 (MRT28), respectively. Loci ranged between 1.2 and 45.6?Mb in length. One family showed linkage to chromosome 8q24.3, and we identified a mutation in TRAPPC9. Our study further highlights the extreme heterogeneity of NS-ARID, and suggests that no major disease gene is to be expected, at least in this study group. Systematic analysis of large numbers of affected families, as presented here, will help discovering the genetic causes of ID. PMID:21629298

Abou Jamra, R; Wohlfart, Sigrun; Zweier, Markus; Uebe, Steffen; Priebe, Lutz; Ekici, Arif; Giesebrecht, Susanne; Abboud, Ahmad; Al Khateeb, Mohammed Ayman; Fakher, Mahmoud; Hamdan, Saber; Ismael, Amina; Muhammad, Safia; Nöthen, Markus M; Schumacher, Johannes; Reis, André

2011-01-01

17

© 2009 Molecular Vision Novel SIL1 mutations in consanguineous Pakistani families mapping to chromosomes 5q31  

E-print Network

Purpose: To investigate the genetic basis of Marinesco-Sjogren syndrome (MSS) in consanguineous Pakistani families. Methods: Two consanguineous Pakistani families with congenital cataract and muscular dystrophy were enrolled for this study. Detailed ophthalmic and systemic examination including slit lamp microscopy, electromyogram and computed tomography scans were performed to characterize the syndrome. Blood samples were collected from affected and unaffected individuals and a genome wide scan consisting of 382 polymorphic microsatellite markers was performed. Coding exons, exon-intron boundaries, 5 ’ UTR, and 3 ’ UTR of the candidate gene SIL1 residing in the linkage interval was sequenced bi-directionally. Results: Clinical examination of the affected members of families 60067 and 60078 revealed features of MSS. The linked interval at chromosome 5q31 harbors SIL1. Sequencing of SIL1 in family 60067 revealed a homozygous substitution; c1240C>T, leading to a premature substitution; p.Q414X. Similarly, sequencing of SIL1 in family 60078 identified a homozygous change; c.274C>T, leading to a non conservative substitution; p.R92W. Conclusion: In conclusion, our data report two novel missense mutations in two consanguineous Pakistani families affected with MSS. Congenital cataracts are one of the major causes of vision loss in children worldwide and are responsible for about one

S. Amer Riazuddin; Laleh Amiri-kordestani; Haiba Kaul; Tariq Butt; Xiaodong Jiao; Sheikh Riazuddin; J. Fielding Hejtmancik; Ophthalmic Genetics

18

Less important role of family size reduction in the recent drastic decrease of consanguineous marriage in Japan  

Microsoft Academic Search

Summary The consanguinity rate in Japan has rapidly decreased during the last 20 years. Possible causes of such decrease were analyzed by comparing chronological changes in the mean number of opposite-sex first cousins and in the rate of first-cousin marriage among 12,448 grandchildren of 891 proband women, using family registers,koseki, at a public office in Nagano Prefecture. The number of

Katumi Tanaka; Reiko Hayase

1977-01-01

19

Down syndrome and consanguinity  

PubMed Central

Background: Among the genetics disorders, Down syndrome (DS) is the major cause of mental retardation, congenital heart and intestinal disease. So far, no certain therapeutic method has been suggested for the treatment of this syndrome. The aim of the current survey was to investigate the frequency of parental consanguinity, maternal age in the patients with DS. Materials and Methods: This study was conducted on 38 consecutive patients with clinically and laboratory confirmed DS who referred to the genetic lab of a referral University Hospital. The G-banding method for karyotyping was employed. Results: The patients were 21 males and 17 females within the age of 16 days to 28 years old. Free trisomy (92.1%, n = 35) was the most common chromosomal abnormality. The frequency of DS was higher among the non-consanguine marriages (71.1%) in comparison with the consanguine marriages (28.9%). Mean age of the mothers in the consanguine marriages (mean = 27.1 ± 6.3) was lower than in the non-consanguine marriages (mean = 31.1 ± 7.7). Conclusion: Higher frequency of DS among the non-consanguine marriages in comparison with the consanguine marriages, may suggest that DS diagnostic tests might be done on all embryos regardless of the parents’ familial relationship. PMID:24523787

Rezayat, Amir Akhavan; Nazarabadi, Mohammad Hassanzadeh; Andalibi, Mohammad Sobhan Sheikh; Ardabili, Hossein Mohaddes; Shokri, Maryam; Mirzaie, Salmeh; Jarahi, Lida

2013-01-01

20

Initial expression of the Papillon-Lefevre syndrome in consanguine family.  

PubMed

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

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

2012-01-01

21

Molecular analysis of a consanguineous Iranian polycystic kidney disease family identifies a PKD2 mutation that aids diagnostics  

PubMed Central

Background Polycystic kidney diseases (PKD) are a group of monogenic disorders that are inherited dominantly (autosomal dominant PKD; ADPKD) or recessively, including, autosomal recessive PKD (ARPKD). A number of recessive, syndromic disorders also involve PKD but have a range of pleiotropic phenotypes beyond the kidney, and are enriched in consanguineous families. Case presentation We describe here a consanguineous Iranian pedigree in which PKD was diagnosed in four generations, but also included cases with additional abnormalities, including mental retardation. We employed molecular screening to reveal the etiology of the PKD. Since the PKD seemed to be dominantly inherited, molecular diagnostics was performed by direct sequencing of the ADPKD genes, PKD1 and PKD2. Clinical and imaging data was collected on family members. The sequence analysis revealed a PKD2 single base-pair deletion, c.1142delG, and segregation was demonstrated in 16 PKD patients from different branches of the family. In keeping with other reports, the PKD2 phenotype in this family was overall mild, and characterized by conserved kidney function, although 12 cases had some evidence of renal insufficiency. Several younger mutation carriers had borderline or no clinical characteristics of ADPKD, while a patient that required a renal transplant at 14 y did not have the PKD2 mutation. Conclusions The molecular analysis of an Iranian family showed that the PKD was due to a PKD2 mutation. The identification of the causative mutation allowed an accurate diagnosis in a number of individuals with equivocal imaging data. Consequently, these patients could be followed appropriately as at-risk individuals. In addition, the PKD2 diagnosis ruled out a syndromic form of PKD as the cause of the additional phenotypes in the family. PMID:24011172

2013-01-01

22

Phenotype of three consanguineous Tunisian families with early-onset retinal degeneration caused by an R91W homozygous mutation in the RPE65 gene  

Microsoft Academic Search

Purpose  To identify the genetic defect, and to phenotype, three consanguineous Tunisian families presenting with early-onset retinal degeneration (EORD).Methods  All accessible family members were included. They underwent blood sampling and ophthalmological examination including, when possible, full-field ERG and pupillometry. A genome-wide linkage analysis was initiated. Mutation analysis of the RPE65 gene within the linked interval was performed by bi-directional sequencing.Results  Eleven out of

Leila El Matri; Aude Ambresin; Daniel F. Schorderet; Aki Kawasaki; Mathias W. Seeliger; Andreas Wenzel; Yvan Arsenijevic; Francis L. Munier

2006-01-01

23

Novel mutations in RDH5 cause fundus albipunctatus in two consanguineous Pakistani families  

PubMed Central

Purpose To identify the underlying genetic causes of fundus albipunctatus (FA), a rare form of congenital stationary night blindness that is characterized by the presence of white dots in the midperiphery of the retina and delayed dark adaptation, in Pakistan. Methods Two families with FA were identified by fundus examination, and genome-wide single nucleotide polymorphism genotyping was performed for two individuals from family A and six individuals from family B. Genotyping data were subsequently used to identify the identical homozygous regions present in the affected individuals of both families using the online homozygosity mapping tool Homozygosity Mapper. Candidate genes selected from the homozygous regions were sequenced. Results Three identical homozygous regions were identified in affected persons of family A (on chromosomes 8, 10, and 12), whereas a single shared homozygous region on chromosome 12 was found in family B. In both families, the homozygous region on chromosome 12 harbored the retinol dehydrogenase 5 (RDH5) gene, in which mutations are known to be causative of FA. RDH5 sequence analysis revealed a novel five base pair deletion, c.913_917delGTGCT (p.Val305Hisfs*29), in family A, and a novel missense mutation, c.758T>G (p.Met253Arg), in family B. Conclusions We identified two novel disease-causing RDH5 mutations in Pakistani families with FA, which will improve diagnosis and genetic counseling, and may even lead to treatment of this disease in these families. PMID:22736946

Ajmal, Muhammad; Khan, Muhammad Imran; Neveling, Kornelia; Khan, Yar Muhammad; Ali, Syeda Hafiza Benish; Ahmed, Waqas; Iqbal, Muhammad Safdar; Azam, Maleeha; den Hollander, Anneke I.; Collin, Rob W.J.; Qamar, Raheel

2012-01-01

24

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

PubMed

Anomalies of eye development can lead to the rare eye malformations microphthalmia and anophthalmia (small or absent ocular globes), which are genetically very heterogeneous. Several genes have been associated with microphthalmia and anophthalmia, and exome sequencing has contributed to the identification of new genes. Very recently, homozygous variations within ALDH1A3 have been associated with autosomal recessive microphthalmia with or without cysts or coloboma, and with variable subphenotypes of developmental delay/autism spectrum disorder in eight families. In a consanguineous family where three of the five siblings were affected with microphthalmia/coloboma, we identified a novel homozygous missense mutation in ALDH1A3 using exome sequencing. Of the three affected siblings, one had intellectual disability and one had intellectual disability and autism, while the last one presented with normal development. This study contributes further to the description of the clinical spectrum associated with ALDH1A3 mutations, and illustrates the interfamilial clinical variation observed in individuals with ALDH1A3 mutations. PMID:24024553

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

2014-09-01

25

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

PubMed Central

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

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

2012-01-01

26

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

PubMed Central

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

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

2010-01-01

27

Cosegregation of a Novel Homozygous CYP11B1 Mutation with the Phenotype of Non-Classical Congenital Adrenal Hyperplasia in a Consanguineous Family  

Microsoft Academic Search

We report a novel missense mutation of CYP11B1 causing non-classical 11?-hydroxylase deficiency in 3 members of a consanguineous Turkish family. Two siblings presented with clinical evidence of precocious pseudopubarche. Biochemistry suggested 11?-hydroxylase deficiency and genetic analysis revealed that they were homozygous for the missense mutation L489S within exon 9 of the CYP11B1 gene. The unaffected parents were heterozygotes for the

C. J. Peters; T. Nugent; L. A. Perry; K. Davies; Y. Morel; W. M. Drake; M. O. Savage; L. B. Johnston

2007-01-01

28

Prevalence and perceptions about consanguineous marriages among patients presenting to family physicians, in 2001 at a Teaching Hospital in Karachi, Pakistan  

Microsoft Academic Search

Aim : Consanguineous marriages are common in Pakistan despite their declining popularity in the developed world. In the present study, a questionnaire based survey was used to record the attitudes and perceptions of consanguineous marriages among the sample population. Methods : A questionnaire was developed to collect information on the acceptability of, and percep- tions about, consanguineous marriages among patients

Waris Qidwai; Iqbal Azam Syed; Faisal M Khan

2003-01-01

29

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

PubMed Central

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

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

2012-01-01

30

Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families.  

PubMed

Split-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identified. The study, presented here, described three consanguineous Pakistani families segregating SHFM in autosomal recessive manner. Linkage in the families was searched by genotyping microsatellite markers and mutation screening of candidate gene was performed by Sanger DNA sequencing. Clinical features of affected members of these families exhibited SHFM phenotype with involvement of hands and feet. Genotyping using microsatellite markers mapped the families to WNT10B gene at SHFM6 on chromosome 12q13.11-q13. Subsequently, sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation (c.1165_1168delAAGT) in one family and 7-bp duplication (c.300_306dupAGGGCGG) in two other families. Structure-based analysis showed a significant conformational shift in the active binding site of mutated WNT10B (p.Lys388Glufs*36), influencing binding with Fzd8. The mutations identified in the WNT10B gene extend the body of evidence implicating it in the pathogenesis of SHFM. PMID:24211389

Aziz, Abdul; Irfanullah; Khan, Saadullah; Zimri, Faridullah Khan; Muhammad, Noor; Rashid, Sajid; Ahmad, Wasim

2014-01-25

31

Clinical and molecular analysis of a large family with three distinct phenotypes of progressive muscular dystrophy  

Microsoft Academic Search

Summary We describe a unique six-generation, highly consanguineous family originating from an isolated mountainous village in the Russian province of Daghestan. Three separate clinical phenotypes of progressive muscular dystrophy were identified in this large family. Seven patients developed a classical limb-girdle variant of muscular dystrophy (LGMD), with disease onset at 15-30 years and loss of ambulation within a 25-year course.

S. N. Illarioshkin; I. A. Ivanova-Smolenskaya; H. Tanaka; N. V. Vereshchagin; E. D. Markova; V. V. Poleshchuk; S. M. Lozhnikova; V. S. Sukhorukov; S. A. Limborska; P. A. Slominsky; K. B. Bulayeva; S. Tsuji

1996-01-01

32

Bleeding disorders in the tribe: result of consanguineous in breeding  

Microsoft Academic Search

OBJECTIVE: To determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages. DESIGN: Cross Sectional Study INTRODUCTION: Countries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia.

Munira Borhany; Zaen Pahore; Zeeshan ul Qadr; Muhammad Rehan; Arshi Naz; Asif Khan; Saqib Ansari; Tasneem Farzana; Muhammad Nadeem; Syed Amir Raza; Tahir Shamsi

2010-01-01

33

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

PubMed Central

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

2013-01-01

34

From "New Genetics" to Everyday Knowledge: Ideas about How Genetic Diseases Are Transmitted in Two Large Brazilian Families  

ERIC Educational Resources Information Center

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected…

Santos, Silvana; Bizzo, Nelio

2005-01-01

35

Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene.  

PubMed

Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA). Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1), might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry) and also in unrelated individuals from the general population (European ancestry). Through identity-by-descent (IBD) mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R) mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009). We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6)). Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry), and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT). Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted. PMID:24520335

Okada, Yukinori; Diogo, Dorothee; Greenberg, Jeffrey D; Mouassess, Faten; Achkar, Walid A L; Fulton, Robert S; Denny, Joshua C; Gupta, Namrata; Mirel, Daniel; Gabriel, Stacy; Li, Gang; Kremer, Joel M; Pappas, Dimitrios A; Carroll, Robert J; Eyler, Anne E; Trynka, Gosia; Stahl, Eli A; Cui, Jing; Saxena, Richa; Coenen, Marieke J H; Guchelaar, Henk-Jan; Huizinga, Tom W J; Dieudé, Philippe; Mariette, Xavier; Barton, Anne; Canhão, Helena; Fonseca, João E; de Vries, Niek; Tak, Paul P; Moreland, Larry W; Bridges, S Louis; Miceli-Richard, Corinne; Choi, Hyon K; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Raj, Towfique; De Jager, Philip L; Raychaudhuri, Soumya; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Siminovitch, Katherine A; Gregersen, Peter K; Mardis, Elaine R; Arayssi, Thurayya; Kazkaz, Layla A; Plenge, Robert M

2014-01-01

36

Was the Darwin/Wedgwood Dynasty Adversely Affected by Consanguinity?  

NSDL National Science Digital Library

Charles Darwin, who was married to his first cousin, Emma Wedgwood, was one of the first experimentalists to demonstrate the adverse effects of inbreeding and to question the consequences of consanguineous mating. He documented the phenomenon of inbreeding depression for numerous plant species, and this caused him to worry about the health of his own children, who were often ill. To determine whether Darwin's fears were justified, we constructed a pedigree of the Darwin/Wedgwood dynasty from the large quantity of genealogical information published on these families. The inbreeding coefficients (F) computed from the pedigree show that Darwin's children were subject to a moderate level of inbreeding (F 5 0.0630), and the progeny of related families had still higher inbreeding values (e.g., F 5 0.1255 for the progeny of Henry Wedgwood, Emma Wedgwood's brother). The analysis of a sample of 25 Darwin/Wedgwood families belonging to four consecutive generations shows a statistically significant positive association between child mortality (death at or before the age of 10 years) and inbreeding coefficient detected by means of nonparametric tests (ÃÂ = 0.309, P = 0.040). Our findings suggest that the high childhood mortality experienced by the Darwin progeny (3 of his 10 children died at age 10 or younger) might be a result of increased homozygosity of deleterious recessive alleles produced by the consanguineous marriages within the Darwin/Wedgwood dynasty.

Tim Berra (The Ohio State University;Dept of Evolution, Ecology and Organismal Biology)

2010-05-03

37

Organ donation consanguinity or universality.  

PubMed

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

Kishore, R R

1996-01-01

38

Arranged marriage, consanguinity and epilepsy  

Microsoft Academic Search

Arranged marriage is where parents choose marital partners for their children. It is a norm in many parts of Asia and Middle East. A marriage is said to be consanguineous where the marriages are solemnized among persons with close biological relations. There is considerable overlap in arranged and consanguineous marriages with many cultures adopting both practices. Recent studies showed that

MM Mehndiratta; B Paul; P Mehndiratta Mehndiratta

39

Consanguinity and hearing impairment in developing countries: a custom to be discouraged.  

PubMed

Consanguineous marriage is a tradition which is commonly practised among Asian, African, and Latin American communities whether they are living in their own countries or settled in Europe or the USA. These communities, in addition to their custom of interrelated marriage, have large families and are a rapidly growing population. The siblings of consanguineous marriages have a significantly higher incidence of autosomal recessive diseases including hearing impairment. Two epidemiological surveys were carried out 10 years apart. There were 6,421 subjects from Riyadh City and 9,540 from all other parts of the Kingdom of Saudi Arabia. A random sample was examined otologically and a questionnaire was filled in that included age, sex, family relation, number of siblings, etc. ENT examination and audiological assessment were performed. Consanguinity was found among 22 per cent as first cousins and 23 per cent as second cousins in the first survey. In the second survey 19 per cent were first cousins and 28 per cent second cousins. The rate of consanguinity was 45 per cent in the first survey and 47 per cent in the second. The prevalence of hereditary sensorineural hearing loss (SNHL) was 66.07 per cent and 36.6 per cent in the first and second survey respectively. The incidence of hereditary hearing impairment is very high in developing countries compared to developed countries. Prevention is essential to reduce the incidence of genetic hearing loss. Consanguinity should be discouraged through health education of the public about the adverse effect of interrelated marriage. Genetic counselling, premarital and antenatal screening are to be applied whenever possible, at least for those at risk of developing genetic diseases including hearing impairment. PMID:12437836

Zakzouk, Siraj

2002-10-01

40

Consanguinity and reproductive health among Arabs  

Microsoft Academic Search

Consanguineous marriages have been practiced since the early existence of modern humans. Until now consanguinity is widely practiced in several global communities with variable rates depending on religion, culture, and geography. Arab populations have a long tradition of consanguinity due to socio-cultural factors. Many Arab countries display some of the highest rates of consanguineous marriages in the world, and specifically

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

2009-01-01

41

Robinow syndrome with parental consanguinity  

Microsoft Academic Search

We describe the clinical features of Robinow syndrome in the first child of a consanguineous Turkish couple. This observation supports the view that severe vertebral anomalies are a feature of the autosomal-recessive form of Robinow syndrome.

D. Glaser; J. Herbst; K. Roggenkamp; W. Tünte; W. Lenz

1989-01-01

42

From new genetics to everyday knowledge: Ideas about how genetic diseases are transmitted in two large Brazilian families  

NASA Astrophysics Data System (ADS)

This study focuses on everyday or lay understandings of inheritance. In the northeastern Brazil, 100 individuals were interviewed in order to describe how they explain the origin of genetic disorders affecting their relatives for several generations. There were involved 60 individuals from a large consanguineous family with many members affected with a neurodegenerative disorder, SPOAN syndrome (spastic paraplegia, optic atrophy and neuropathy), and 40 individuals of another family living with neurofibromatosis type 1 (NF1). The results indicate that families here studied have built narratives to explain the origin of genetic diseases, saying that an ancestor infected with syphilis gave rise to disorders and birthmarks transmitted to descendents.

Santos, Silvana; Bizzo, Nelio

2005-07-01

43

Consanguinity and increased risk for schizophrenia in Egypt  

PubMed Central

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

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

44

Consanguinity associated with increased risk for bipolar I disorder in Egypt.  

PubMed

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 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

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; El Sheshtawy, Eman; El-Boraie, Osama; El-Chennawi, Farha; Devlin, Bernie; Nimgaonkar, Vishwajit L

2009-09-01

45

The Prevalence of Congenital Malformations and its Correlation with Consanguineous Marriages  

PubMed Central

Objectives Consanguinity has been a long standing social habit among some Iranians. This study is aimed at determining the role of consanguinity on congenital malformations and the correlation of inbreeding coefficient with anomalies. Methods In this cross-sectional study, all the newborns who were born during 9 months period from April to December 2008. (n=1195) at Shahid Sadoughi hospital, Yazd, Iran were studied. Results From 1195 neonates, 300 (25%) were from consanguineous marriages and 895 (75%) were from non-familial marriages. From 45 cases with anomalies, 34 (2.8%) cases were from familial marriages, while only 11 (0.9%) cases were from non-familial marriages. There was a significant correlation between parental marriages and the prevalence of anomaly (p=0.018). Conclusion The prevalence of congenital anomalies was mostly observed in consanguineous marriages compared to non consanguineous marriages. PMID:22125696

Tayebi, Naeimeh; Yazdani, Katayon; Naghshin, Nazila

2010-01-01

46

On Some Novel Aspects of Consanguineous Marriages  

Microsoft Academic Search

Consanguineous marriages, often viewed as incestuous and objectionable, are more widespread than commonly perceived. They integrate multiple facets of human adaptation: economic, cultural and genetic. The widely touted explanation for the origin and persistence of consanguinity is that it provides many socioeconomic benefits; however, this view may be too simplistic. The bias against consanguinity may preclude an objective understanding of

S. Denic; N. Nagelkerke; M. M. Agarwal

2011-01-01

47

The Perils of SNP Microarray Testing: Uncovering Unexpected Consanguinity  

PubMed Central

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

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

2013-01-01

48

A novel insertion mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene underlies Grebe-type chondrodysplasia in a consanguineous Pakistani family  

Microsoft Academic Search

BACKGROUND: Grebe-type chondrodysplasia (GCD) is a rare autosomal recessive syndrome characterized by severe acromesomelic limb shortness with non-functional knob like fingers resembling toes. Mutations in the cartilage-derived morphogenetic protein 1 (CDMP1) gene cause Grebe-type chondrodysplasia. METHODS: Genotyping of six members of a Pakistani family with Grebe-type chondrodysplasia, including two affected and four unaffected individuals, was carried out by using polymorphic

Sulman Basit; Syed Kamran-ul-Hassan Naqvi; Naveed Wasif; Ghazanfar Ali; Muhammad Ansar; Wasim Ahmad

2008-01-01

49

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

PubMed Central

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

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

2014-01-01

50

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

PubMed

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

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

2014-04-01

51

Bleeding disorders in the tribe: result of consanguineous in breeding  

PubMed Central

Objective To determine the frequency and clinical features of bleeding disorders in the tribe as a result of consanguineous marriages. Design Cross Sectional Study Introduction Countries in which consanguinity is a normal practice, these rare autosomal recessive disorders run in close families and tribes. Here we describe a family, living in village Ali Murad Chandio, District Badin, labeled as haemophilia. Patients & Methods Our team visited the village & developed the pedigree of the whole extended family, up to seven generations. Performa was filled by incorporating patients, family history of bleeding, signs & symptoms, and bleeding from any site. From them 144 individuals were screened with CBC, bleeding time, platelet aggregation studies & RiCoF. While for PT, APTT, VWF assay and Factor VIII assay, samples were kept frozen at -70 degrees C until tested. Results The family tree of the seven generations comprises of 533 individuals, 63 subjects died over a period of 20 years and 470 were alive. Out of all those 144 subjects were selected on the basis of the bleeding history. Among them 98(68.1%) were diagnosed to have a bleeding disorder; 44.9% patients were male and 55.1% patients were female. Median age of all the patients was 20.81, range (4 months- 80 yrs). The results of bleeding have shown that majority had gum bleeding, epistaxis and menorrhagia. Most common bleeding disorder was Von Willebrand disease and Platelet functional disorders. Conclusion Consanguineous marriages keep all the beneficial and adversely affecting recessive genes within the family; in homozygous states. These genes express themselves and result in life threatening diseases. Awareness, education & genetic counseling will be needed to prevent the spread of such common occurrence of these bleeding disorders in the community. PMID:20822539

2010-01-01

52

Consanguinity pattern and heritability of Vitiligo in Arar, Saudi Arabia  

PubMed Central

Context: Epidemiological studies have shown that vitiligo is a complex trait, involving combinations of pathogenic effects of multiple susceptibility genes as well as environmental risk factors. Aim: To observe whether consanguinity increased the incidence of vitiligo in Saudi patients from Arar. Patients and Methods: This study included 69 Saudi patients with vitiligo and their families. These patients, selected from the experience specialist dermatology center in Arar, from April 2011 to 2012, were interviewed by a dermatologist to confirm the diagnosis and complete a questionnaire. Results: A total of 69 patients, 40 males and 29 females were selected. Their mean age was 34.5 ± 11.8 years with the median age of 23 years. The mean age at onset of disease was 27.9 ± 12.9 years. The mean duration of the disease was 9.7 ± 5.3 years. The frequency of focal, vulgaris, universal, and acrofacial subtypes was 22 (31.9%), 21 (30.4%), 8 (11.6%), and 18 (26.1%), respectively. A positive family history of vitiligo was obtained in 45 (65.2%) cases. A comparison of the frequency of vitiligo among siblings in relation to the general population was more in accord with the multifactorial model. Conclusion: Consanguinity in marriage increases the incidence of the disease. Therefore, genetic counseling and premarital examination would be important contributions to lower the prevalence of vitiligo. PMID:24696629

Alenizi, Dhaifallah A.

2014-01-01

53

A MEASURE OF CONSANGUINITY Fred Richman  

E-print Network

. * * For simple relationships the consanguineal distance specializes to the civil * *degree, less two if the relationship goes through full siblings. This measure is * *deduced from axioms motivated is a mixture of equal* * parts of the blood of his two parents. We use this model as the motivation for our

Richman, Fred

54

A MEASURE OF CONSANGUINITY Fred Richman  

E-print Network

multiple kinship connections. For simple relationships the consanguineal distance specializes to the civil degree, less two if the relationship goes through full siblings. This measure is deduced from axioms of his two parents. We use this model as the motivation for our computa- tions since it seems to re ect

Richman, Fred

55

A MEASURE OF CONSANGUINITY Fred Richman  

E-print Network

multiple kinship connections. For simple relationships the consanguineal distance specializes to the civil degree, less two if the relationship goes through full siblings. This measure is deduced from axioms of the blood of his two parents. We use this model as the motivation for our computa­ tions since it seems

Richman, Fred

56

Consanguineous marriage and reproduction in Beirut, Lebanon.  

PubMed Central

Effects of consanguineous marriages on couples' fertility and on offspring mortality were investigated in Beirut through a population-based health survey of 2,752 households. A multistage random sampling procedure was used, and information was obtained from all ever-married women in the household about their reproductive performance and genealogical relationship with spouse; demographic and socioeconomic information was also recorded. Twenty-five percent of all marriages were between relatives, and the spouses were first cousins in approximately 57% of all consanguineous marriages. Total pregnancies, live births, and living children were significantly higher among consanguineous couples than among nonconsanguineous ones, as was the proportion dead among children ever born. However, no difference remained in either fertility or mortality, when allowance was made for socioeconomic status, religious affiliation, and marriage duration. The issue of confounding is discussed, and the lack of significant pattern in the final analysis is interpreted as resulting from a long-term practice of consanguineous marriages. PMID:3400644

Khlat, M

1988-01-01

57

Consanguinity and Its Sociodemographic Differentials in Bhimber District, Azad Jammu and Kashmir, Pakistan  

PubMed Central

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

Jabeen, Nazish

2014-01-01

58

Does consanguinity increase the risk of schizophrenia? Study based on primary health care centre visits  

PubMed Central

Background Consanguinity has been suggested as a risk factor for the development of schizophrenia in offspring in some Middle Eastern countries. Aim The purpose of this study was to review the frequency, pattern of parental consanguinity, and family history of schizophrenia among schizophrenia patients in Qatar, and to determine their impact on the associated risk factors. Design This is a cross-sectional study which was conducted between January 2009 and December 2010, in the setting of primary health care (PHC) centres of the Supreme Council of Health, State of Qatar. Subjects A total of 1491 patients aged 18–55 years were approached, of whom 1184 individuals agreed to participate in the study, giving a response rate of 79.4%. Methods The study was based on face-to-face interviews using a specially designed questionnaire that covered sociodemographic characteristics and genetic and other biological factors (e.g. obstetric complications), and a diagnostic screening questionnaire which consisted of six questions about the symptoms of schizophrenia. The diagnostic screening questionnaire was reviewed and used to calculate the final score, which determined a provisional diagnosis. The psychiatrists discussed the psychiatric diagnosis and confirmed it using DSM-IV criteria. The degree of consanguinity between the patient's parents was recorded. Consanguinity was evaluated based on the coefficient of inbreeding (F), which is the probability of homozygosity. Results More than half of the schizophrenia patients were female (57.1%) and over 45 years of age (62.5%). A family history of schizophrenia was significantly more common in parents of schizophrenia patients than in the Arab population without schizophrenia (24.6% vs. 17.1%; P = 0.038). Parental consanguinity was elevated among the patients with schizophrenia (41.3%) with a higher mean coefficient of inbreeding (0.04356 ± 0.028) than in non-schizophrenic subjects (28.7%) with a lower mean coefficient of inbreeding (0.0298 ± 0.035). Schizophrenia diagnoses were more frequent among the offspring of consanguineous parents than among the offspring of non-consanguineous parents. Conclusion The substantial risk observed in the present study reveals that consanguinity is an important risk factor for schizophrenia in Qatar. In addition, the study confirms that the higher familial risks provide strong genetic epidemiological evidence for the overall heritable effects in the aetiology of schizophrenia. PMID:24294299

2012-01-01

59

Large Constituent Families Help Children Parse Compounds  

ERIC Educational Resources Information Center

The family size of the constituents of compound words, or the number of compounds sharing the constituents, has been shown to affect adults' access to compound words in the mental lexicon. The present study was designed to see if family size would affect children's segmentation of compounds. Twenty-five English-speaking children between 3;7 and…

Krott, Andrea; Nicoladis, Elena

2005-01-01

60

Race, consanguinity and social features in Birmingham babies: a basis for prospective study.  

PubMed Central

STUDY OBJECTIVE--The aim of the study was to investigate the influence of consanguinity on children's health. DESIGN--The study is a prospective survey from birth to five years of a cohort of babies born in a multiracial community. This report details the initial findings on consanguinity. SETTING--Participating families live predominantly in three health districts of Birmingham, and were recruited in three local maternity hospitals. PARTICIPANTS--Babies of 2432 European mothers, 509 Afro-Caribbean mothers, 625 Indian mothers, 956 Pakistani mothers, and 216 Bangladeshi mothers have been enrolled in the study. Eighty mothers refused to participate. MEASUREMENTS AND RESULTS--Sociodemographic information was obtained using a structured questionnaire administered at interview. Interview data were supplemented with obstetric information from the medical records. The highest prevalence of parental consanguinity was in Pakistani Muslims (69%), whereas in Muslims from other countries it was 23%, and it was less than 1% in non-Muslims. In the majority of consanguineous Muslim pedigrees the degree of inbreeding was greater than that for first cousin parents. CONCLUSIONS--This prospective study will allow an assessment to be made about any ill health in childhood arising from parental consanguinity, about whether screening programmes are indicated for particular autosomal recessive diseases, and about whether premarital health education might be beneficial. The study has also documented parental ages in different races and this, together with the levels of parental consanguinity in all races, will be useful in genetic methods for assessing the frequency of recessive genes, the possibility of genetic heterogeneity, and whether or not parental age effect exists for new mutations of specific genetic disorders. PMID:2370500

Bundey, S; Alam, H; Kaur, A; Mir, S; Lancashire, R J

1990-01-01

61

A large family of bacterial activator proteins.  

PubMed Central

At least nine different bacterial proteins belong to the LysR family. The gene sequence for one of these proteins is presented here. Six others (Escherichia coli LysR, IlvY, CysB; Salmonella typhimurium MetR; Rhizobium NodD; and Enterobacter cloacae AmpR) are known to activate other genes. Based on sequence alignments, each member of this family is predicted to have a helix-turn-helix DNA binding motif near its amino terminus. The combined evidence indicates that all nine proteins are related by common ancestry, are similarly folded, and are not detectably related to other known bacterial regulatory proteins. The DNA database searching procedure and other methods used in this study should be useful in detecting other groups of related proteins. PMID:3413113

Henikoff, S; Haughn, G W; Calvo, J M; Wallace, J C

1988-01-01

62

Consanguinity and Birth Defects in the Jerusalem Perinatal Study Cohort  

Microsoft Academic Search

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

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

2008-01-01

63

Relationship between consanguinity and depression in a south Indian population  

PubMed Central

A Pilot study was Carried out to study the association of consanguinity marriage with depression. It was observed that the consanguinity of marriage was associated with depression. The odds ratio was 5.66 (CI: 2.42-13.54). The age and sex had an association with depression. The age and sex adjusted odds ratio of consanguinity marriage was 7.66 (CI: 3.93-19.45) indicating that it is independently associated with depression. PMID:19742204

Rao, T. S. Sathyanarayana; Prabhakar, A. K.; Jagannatha Rao, K. S.; Sambamurthy, K.; Asha, M. R.; Ram, Dushad; Nanda, Ananya

2009-01-01

64

Consanguineous unions and child health in the State of Qatar.  

PubMed

The aim of the study was to estimate the prevalence and sociodemographic predictors of consanguineous unions in the State of Qatar and to assess the association between consanguinity, fertility and child health. A representative sample of 1800 Qatari women aged > or =15 years was approached for the study. Of these, 1515 (84.2%) women agreed to participate. The consanguineous marriage rate was 54.0% with estimated population confidence limits of 52.3-55.7%. First cousin unions were the most common form of cousin marriage. The level of parental consanguinity (both in the respondent's parents and her parents-in-law) was quite high. In a multivariable analysis, both education of the respondent and her husband as well as parental consanguinity were found to be strong predictors of consanguineous unions in the index generation. Although fertility was high in both groups, the mean number of pregnancies was somewhat higher in respondents with first cousin unions. Concomitantly they also had a slighter higher rate of livebirths than women in non-consanguineous unions. The occurrence of asthma, mental retardation, epilepsy and diabetes was significantly more common in offspring of all consanguineous than non-consanguineous couples. PMID:16911015

Bener, Abdulbari; Hussain, Rafat

2006-09-01

65

Consanguineous marriages in the province of Antalya, Turkey  

Microsoft Academic Search

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

Ö. M. Alper; H. Erengin; A. E Manguo?lu; T. Bilgen; Z. Çetin; N. Dedeo?lu; G. Lüleci

2004-01-01

66

Autosomal dominant stationary night-blindness. A large family rediscovered.  

PubMed

In 1909, 2 years after the famous publication by Nettleship, a large family with congenital stationary night-blindness of the 'Nougaret type' was published by the Danish district surgeon, Sigurd Rambusch. In 1990 the 'Rambusch family', still resident in the original area, was sought out and rediscovered, at which time the reconstructed part of the pedigree comprised more than 200 affected persons in 11 generations. Dark adaptometry and electroretinography were performed on a few affected family members, including a descendant with a uniocular affection. The pedigree is presented and recordings of dark adaptation courses and electroretinographical responses from a few family members are demonstrated. PMID:1789082

Rosenberg, T; Haim, M; Piczenik, Y; Simonsen, S E

1991-12-01

67

Consanguinity and polygenic diseases: a model for antibody deficiencies.  

PubMed

Primary immunodeficiencies represent a heterogeneous group of disorders of the immune system, predisposing to various types of infections. Among them, common variable immunodeficiency is the most common symptomatic antibody deficiency. It includes several different forms characterized by defects in the terminal stage of B lymphocyte differentiation, leading to markedly reduced immunoglobulin serum levels and increased susceptibility to bacterial infections. The clinical phenotype is complex, including autoimmunity, granulomatous inflammation, lymphoproliferative disorders and malignancies. Rare autosomal recessive mutations in a number of single genes have recently been reported. However, the underlying genetic defects remain unknown in the majority of cases. In order to seek new genes responsible for the disease, we studied a consanguineous Italian family through exome sequencing combined with homozygosity mapping. Six missense homozygous variants passed our filtering selection and at least two of them were associated with some aspects of the pathological phenotype. Our data remark the complexity of immune system disorders and emphasize the difficulty to understand the significance of genetic results and their correlation with the disease phenotype. PMID:25060277

Di Pierro, Valentina; Zuntini, Roberta; Cancrini, Caterina; Finocchi, Andrea; Angelino, Giulia; Rossi, Paolo; Ferrari, Simona

2014-01-01

68

SNP array-based homozygosity mapping reveals MCPH1 deletion in family with autosomal recessive mental retardation and mild microcephaly  

Microsoft Academic Search

Very little is known about the molecular basis of autosomal recessive MR (ARMR) because in developed countries, small family\\u000a sizes preclude mapping and identification of the relevant gene defects. We therefore chose to investigate genetic causes of\\u000a ARMR in large consanguineous Iranian families. This study reports on a family with six mentally retarded members. Array-based\\u000a homozygosity mapping and high-resolution microarray-based

Masoud Garshasbi; Mohammad Mahdi Motazacker; Kimia Kahrizi; Farkhondeh Behjati; Seyedeh Sedigheh Abedini; Sahar Esmaeeli Nieh; Saghar Ghasemi Firouzabadi; Christian Becker; Franz Rüschendorf; Peter Nürnberg; Andreas Tzschach; Reza Vazifehmand; Fikret Erdogan; Reinhard Ullmann; Steffen Lenzner; Andreas W. Kuss; H. Hilger Ropers; Hossein Najmabadi

2006-01-01

69

Airfoil family design for large offshore wind turbine blades  

NASA Astrophysics Data System (ADS)

Wind turbine blades size has scaled-up during last years due to wind turbine platform increase especially for offshore applications. The EOLIA project 2007-2010 (Spanish Goverment funded project) was focused on the design of large offshore wind turbines for deep waters. The project was managed by ACCIONA Energia and the wind turbine technology was designed by ACCIONA Windpower. The project included the design of a wind turbine airfoil family especially conceived for large offshore wind turbine blades, in the order of 5MW machine. Large offshore wind turbines suffer high extreme loads due to their size, in addition the lack of noise restrictions allow higher tip speeds. Consequently, the airfoils presented in this work are designed for high Reynolds numbers with the main goal of reducing blade loads and mantainig power production. The new airfoil family was designed in collaboration with CENER (Spanish National Renewable Energy Centre). The airfoil family was designed using a evolutionary algorithm based optimization tool with different objectives, both aerodynamic and structural, coupled with an airfoil geometry generation tool. Force coefficients of the designed airfoil were obtained using the panel code XFOIL in which the boundary layer/inviscid flow coupling is ineracted via surface transpiration model. The desing methodology includes a novel technique to define the objective functions based on normalizing the functions using weight parameters created from data of airfoils used as reference. Four airfoils have been designed, here three of them will be presented, with relative thickness of 18%, 21%, 25%, which have been verified with the in-house CFD code, Wind Multi Block WMB, and later validated with wind tunnel experiments. Some of the objectives for the designed airfoils concern the aerodynamic behavior (high efficiency and lift, high tangential coefficient, insensitivity to rough conditions, etc.), others concern the geometry (good for structural design, compatibility for the different airfoil family members, etc.) and with the ultimate objective that the airfoils will reduce the blade loads. In this paper the whole airfoil design process and the main characteristics of the airfoil family are described. Some force coefficients for the design Reynolds number are also presented. The new designed airfoils have been studied with computational calculations (panel method code and CFD) and also in a wind tunnel experimental campaign. Some of these results will be also presented in this paper.

Méndez, B.; Munduate, X.; San Miguel, U.

2014-06-01

70

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

PubMed

This paper uses a wealth shock from the construction of a flood protection embankment in rural Bangladesh coupled with data on the universe of all 52,000 marriage decisions between 1982 and 1996 to examine changes in marital prospects for households protected by the embankment relative to unprotected households living on the other side of the river. We use difference-in-difference specifications to document that brides from protected households commanded larger dowries, married wealthier households, and became less likely to marry biological relatives. Financial liquidity-constrained households appear to use within-family marriage (in which one can promise ex-post payments) as a form of credit to meet up-front dowry demands, but the resultant wealth shock for households protected by the embankment relaxed this need to marry consanguineously. Our results shed light on the socioeconomic roots of consanguinity, which carries health risks for offspring but can also carry substantial benefits for the families involved. PMID:23619998

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

2013-10-01

71

Letters to the Editor CONSANGUINITY AND HETEROGENEITY: CYSTIC FIBROSIS  

E-print Network

Letters to the Editor CONSANGUINITY AND HETEROGENEITY: CYSTIC FIBROSIS NEED NOT BE HOMOGENEOUS, ET AL.: Incidence in Italy, genetic heterogeneity, and segregation analysis of cystic fibrosis. Am J Hum Genet 37:338-349, 1985 2. Tsui LC, BUCHWALD M, BARKER D, ET AL.: Cystic fibrosis locus defined

Botstein, David

72

The frequency of consanguineous marriage among British Pakistanis  

Microsoft Academic Search

An enquiry answered by 100 randomly selected British Pakistani mothers in the postnatal wards of two hospitals in West Yorkshire showed that 55 were married to their first cousins, while in only 33 cases had their mother been married to her first cousin. This suggests an increasing rate of consanguineous marriage in this relatively small group, by contrast with the

A Darr; B Modell

1988-01-01

73

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

PubMed Central

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, ?=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.???Keywords: congenital glaucoma; CYP1B1; gene; genetic counselling PMID:10851252

Martin, S; Sutherland, J.; Levin, A.; Klose, R.; Priston, M.; Heon, E.

2000-01-01

74

Genetic Counseling in Southern Iran: Consanguinity and Reason for Referral  

Microsoft Academic Search

Population based genetic counseling that promotes public health goals is an appropriate health care service. The genetic counseling\\u000a center in Shiraz, southern Iran serves most of the clients in the region. During a 4-year period, 2,686 couples presented\\u000a for genetic counseling. Data files revealed that 85% had consanguineous relationships (1.5% double first cousin, 74% first\\u000a cousin, 8% second cousin, 1.5%

Mohsen Fathzadeh; Mohammad Ali Babaie Bigi; Masood Bazrgar; Majid Yavarian; Hamid Reza Tabatabaee; Seyed Mohammad Akrami

2008-01-01

75

Are families poor because they are large or are they large because they are poor?  

PubMed

In the Philippines time allocation studies suggest that children cost considerable amounts of time and energy on the part of the mother and other siblings in addition to direct financial outlays which figure prominently. Yet, these costs seem to be compensated for by economic and noneconomic benefits. The time costs of children are moderated to the extent that mother's time has a low opportunity cost, given lack of marketable skills or sheer absence of employment opportunities. It is at the expense of investment in human capital (in terms of education and health) that economic benefits from child labor are forthcoming. As neither unemployment of the mother nor child labor is desirable, it would seem that economic benefits from children are expensive. The child's mental and physical development tends to be impaired due to deficient health, nutrition, and education inputs because family resources and parental care have to be spread so thinly among the many competing demands of the large family. Mother's health is negatively affected by frequent and closely spaced pregnancies, and she is effectively prevented from actual or potential participation in development. It is to these less immediate and not directly observable disadvantages of a large family that parents must be sensitized so that they will realize the need to limit family size. From the social perspective, the population program may be viewed as a strategy for human resource development. The challenge to policymakers has become formidable. Due to rapidly increasing population, the need to telescope the reduction of income inequality and poverty has become urgent. Continuing population growth tends to nullify whatever advances are made toward the distributional objective. Population and development policy needs to be directed to the poor in rural areas in general and more specifically to the rural poor in the backward regions of the Visayas, Bicol, Bocos, and Northern Mindanao. Given the extreme poverty of these groups, the family planning programs would seem to require complementary development inputs such as health, nutrition, and education. A less expensive strategy may be sufficient for the comparatively better off regions and social groups. PMID:12279386

Pernia, E M

1982-01-01

76

Familial Paroxysmal Dystonic Choreoathetosis: Clinical Findings in a Large Japanese Family and Genetic Linkage to 2q  

Microsoft Academic Search

Patients and Methods: We studied a large Japanese family in which at least 17 members in 6 generations have been affected by PDC. We interviewed and examined 26 family members, 8 of whom revealed choreoathetosis- like and dystonialike involuntary movement and 1 of whom revealed no involuntary movement but only muscle stiffness such as the aura of paroxysmal dystonic cho-

Hirotaka Matsuo; Keiko Kamakura; Masaaki Saito; Masamichi Okano; Terumasa Nagase; Yutaka Tadano; Ken-ichi Kaida; Akira Hirata; Norikazu Miyamoto; Toshihiro Masaki; Ryohji Nakamura; Kazuo Motoyoshi; Hajime Tanaka; Shoji Tsuji

1999-01-01

77

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

PubMed

The practice of consanguineous marriage has been the culturally preferred form of marriage in most Arab and the Middle Eastern countries, including Oman, but due to a paucity of population-based data in the past there is a dearth of information about its form and dynamics in Oman. Recent national-level surveys allow this gap to be filled. This paper examines the prevalence, trends and determinants of consanguineous marriages in Oman using data from the 2000 Oman National Health Survey. The results indicate a very high prevalence of consanguineous marriage in Oman, as more than half (52%) of marriages are consanguineous. First cousin unions are the most common type of consanguineous unions, constituting 39% of all marriages and 75% of all consanguineous marriages. The study observed various patterns of consanguinity, some of them common with other Arab nations, and some unique in nature. Women's age at marriage, employment, place of childhood residence and geographical region appear to be significant determinants of consanguineous marriages. Consanguineous marriage shows a strong association with marital stability, early age at marriage and early-age childbearing. There has been no appreciable change in the prevalence of consanguineous unions in Oman over the last four decades despite massive socioeconomic development and modernization. However, recent marriage cohorts show slight declining trends. The results suggest that consanguinity is likely to remain stable in the future or decline at a slow rate. Specific health education and genetic counselling should be followed in line with WHO recommendations to minimize the negative health consequences of consanguinity for child health. PMID:22317781

Islam, M Mazharul

2012-09-01

78

Diagnosis of Bardet-Biedl Syndrome in Consecutive Pregnancies Affected with Echogenic Kidneys and Polydactyly in a Consanguineous Couple  

PubMed Central

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathic human genetic disorder with variable expression that is difficult to diagnose in pregnancy without known risk factors. Homozygosity testing has been shown to be a useful tool in identifying BBS mutations and candidate genes in affected individuals. We present the first case of prenatal diagnosis of BBS in consecutive pregnancies aided by homozygosity testing via SNP microarray analysis. This case demonstrates a novel approach to the evaluation of recurrent echogenic kidneys in consanguineous couple with no significant family history. PMID:23533844

Baker, Tieneka M.; Sturm, Erica L.; Turner, Clesson E.; Petersen, Scott M.

2013-01-01

79

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

PubMed

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

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

2014-07-01

80

Fertility Related Attitudes of Minority Mothers with Large and Small Families.  

ERIC Educational Resources Information Center

The relationship between certain attitudes and the levels of fertility in five cultural groups was explored in this study. The group studied were blacks, Cubans, American Indians, migrant Chicanos, and white Protestants. Mothers, aged 35-45, with one or two children (small family) or five children (large family) were compared. Attitudes measured…

Linn, Margaret W.; And Others

81

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

PubMed

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

Krishan, G

1986-05-01

82

The mushroom family Psathyrellaceae: Evidence for large-scale polyphyly of the genus Psathyrella  

E-print Network

(Smith, 1972). Species of Psathyrella are often found on decaying logs, woody debris, humus, or soilThe mushroom family Psathyrellaceae: Evidence for large-scale polyphyly of the genus Psathyrella. gracilis, formed a large clade with Coprinellus, which appeared to be derived from within Psathyrella

Hibbett, David S.

83

Consanguinity Mapping of Congenital Heart Disease in a South Indian Population  

Microsoft Academic Search

BackgroundParental 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

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

2010-01-01

84

Trends of consanguineous marriages in a Sunni Muslim population of West Bengal, India.  

PubMed

The Muslim population of the Chaltaberia village in the district of South 24 Parganas in West Bengal is divided into several wards (paras) inhabited by people of specific surnames. The frequency of endogamous marriages within surnames is greater than randomly expected ones. An incomplete reproductive isolation is observed among the five dominant surnames. Consanguineous marriages occur more often outside the village than inside. Leaving out marriages between long distances, a small median distance of 6.36 km is recorded. The neighborhood area works up to be 552.2 km2, which is rather small. There is an underlying process of breeding isolation by distance. A generation length of 21 years has been used for examining the temporal change in consanguineous marriages and inbreeding, which generally appears to increase. There is a general trend of decline in consanguineous marriages towards the southern part of West Bengal and eastern part of Assam among the Bengalee Muslims. The frequency of consanguineous marriages is 7.3% out of all marriages (N=1153) that have taken place in six generations in the population. The first cousin marriage is nearly 50% of all marriages. Patrilineal marriages are common in marriages between second and third cousins. An increase of consanguineous marriages in the younger generation was observed, but the total frequency agrees with a general trend of a decline in the frequency of consanguineous marriages among the Muslims in this part of India. PMID:17987905

Mukherjee, D P; Das, Sanghamitra; Banik, Sudip Datta

2007-09-01

85

Age correlation between mates and average consanguinity in age-structured human populations.  

PubMed Central

When population geneticists wish to determine the genetic consequences of some aspect of mating behavior, it is often necessary to compare observed levels of consanguinity to the level expected when mating is random with respect to the factor being studied. Expectations under random mating are often derived from discrete generation models that ignore age structure. Observed frequencies of consanguineous matings are due to processes that are continuous in time and are affected by variables that are functions of age structure. The extent to which this discrepancy between the models and reality might distort conclusions drawn from comparisons of observed and expected behavior has received insufficient attention. One potential source of error is the tendency for people to choose mates whose ages differ from their own by a certain amount; this tendency influences the frequency of consanguineous matings. Age correlation between mates should therefore also affect average consanguinity between mates and average inbreeding in the population. Expected levels of consanguinity might then differ depending on whether or not age structure has been taken into account. Hajnal developed a model that predicts the frequencies of consanguineous matings in age-structured populations. Hajnal's model is extended here to include relationships that are defined by lineal descent as well as by common ancestry, and to allow calculation of the frequencies of consanguineous matings in the absence of age correlation between mates. The extended model is then used to determine the effect of age correlation between mates on average consanguinity under various sets of conditions. The magnitude of this effect depends on the degree to which the increased frequency of some types of consanguineous matings is offset by the decrease in other types of matings. There is a fairly wide range of conditions under which this compensation is nearly complete and therefore under which the overall effect of age correlation is small. But the size of this effect is sensitive to many factors, especially the distribution of age differences between mates and the variances of ages at maternity and paternity. Under some conditions, age correlation between mates will have a substantial effect on average consanguinity. PMID:6614010

Leslie, P W

1983-01-01

86

Polar Localization of the Autotransporter Family of Large Bacterial Virulence Proteins  

Microsoft Academic Search

Autotransporters are an extensive family of large secreted virulence-associated proteins of gram-negative bacteria. Secretion of such large proteins poses unique challenges to bacteria. We demonstrate that autotrans- porters from a wide variety of rod-shaped pathogens, including IcsA and SepA of Shigella flexneri, AIDA-I of diffusely adherent Escherichia coli, and BrkA of Bordetella pertussis, are localized to the bacterial pole. The

Sumita Jain; Peter van Ulsen; Inga Benz; M. Alexander Schmidt; Rachel Fernandez; Jan Tommassen; Marcia B. Goldberg

2006-01-01

87

A Large Multiple Endocrine Neoplasia Type 1 Family with Clinical Expression Suggestive of Anticipation  

Microsoft Academic Search

We describe a large multigenerational multiple endocrine neopla- sia Type 1 (MEN1) family with clinical expression suggestive of an- ticipation. In the second and third generations, two deceased obligate gene carriers died at the ages of 85 and 76 without the history of MEN1, whereas two other living gene carriers above the age of 65 have had no clinical evidence

SOPHIE GIRAUD; HELENE CHOPLIN; BIN TEAN TEH; JAMES LESPINASSE; ANNE JOUVET; FRANCOISE LABAT-MOLEUR; GILBERT LENOIR; BEATRICE HAMON; PATRICK HAMON; ALAIN CALENDER

2010-01-01

88

Hepatic vascular malformations in hereditary hemorrhagic telangiectasia: Doppler sonographic screening in a large family  

Microsoft Academic Search

Background\\/Aims: The prevalence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia has been estimated in the literature on clinical criteria, thus giving unreliable data. In our study the presence of hepatic vascular malformations in hereditary hemorrhagic telangiectasia was evaluated in a large Italian family by using Doppler sonography as screening technique. Doppler sonographic findings were compared to computed tomography and

Elisabetta Buscarini; Luigi Buscarini; Cesare Danesino; Mauro Piantanida; Giuseppe Civardi; Pietro Quaretti; Sandro Rossi; Michele Di Stasi; Matteo Silva

1997-01-01

89

Genetic heterogeneity in psoriasis vulgaris based on linkage analyses of a large family material  

SciTech Connect

Information on psoriasis among parents and siblings in 14,008 families has been collected. On the basis of this material, evidence for monogenetic autosomal recessive inheritance of psoriasis has recently been presented. Indications from more than one type of non-pustular psoriasis has been obtained from the population genetic data. Molecular genetic linkage analysis of psoriasis to a number of polymorphic genetic markers for a large number of families has been made. It is apparent that there is genetic heterogeneity in a psoriasis population with regard to psoriasis genes. Using the computer program Linkage 5.0 and a formula for heterogeneity, a lodscore over 3.0 for one locus has been obtained. This locus has further been confirmed by several other markers in the vicinity. The locus found is linked to slightly over half of the families, indicating that there are more genetically independent types of psoriasis. The age at onset of those families that are apparently linked to this locus have a slightly higher age at onset than those not linked to that locus but with a considerable overlap. In spite of close coverage of the whole chromosomes number 6 and 17, no linkage has been found in this regions. This indicates that neither the HLA region nor the region earlier found to be involved in one family with psoriasis are primarily involved in our families.

Wahlstroem, J.; Swanbeck, G.; Inerot, A. [ Univ. of Goeteborg (Sweden)] [and others

1994-09-01

90

Phenotype-Genotype Correlation in Wilson Disease in a Large Lebanese Family: Association of c.2299insC with Hepatic and of p. Ala1003Thr with Neurologic Phenotype  

PubMed Central

Genotype phenotype correlations in Wilson disease (WD) are best established in homozygous patients or in compound heterozygous patients carrying the same set of mutations. We determined the clinical phenotype of patients with WD carrying the c.2298_2299insC in Exon 8 (c.2299insC) or the p. Ala1003Thr missense substitution in Exon 13 mutations in the homozygous or compound heterozygous state. We investigated 76 members of a single large Lebanese family. Their genotypes were determined, and clinical assessments were carried out for affected subjects. We also performed a literature search retrieving the phenotypes of patients carrying the same mutations of our patients in the homozygous or compound heterozygous state. There were 7 consanguineous marriages in this family and the prevalence of WD was 8.9% and of carriers of ATP7B mutation 44.7%. WD was confirmed in 9 out of 76 subjects. All 9 had the c.2299insC mutation, 5 homozygous and 4-compound heterozygous with p. Ala1003Thr. Six of our patients had hepatic, 2 had neurologic and 1 had asymptomatic phenotype. Based on our data and a literature review, clear phenotypes were reported for 38 patients worldwide carrying the c.2299insC mutation. About 53% of those have hepatic and 29% have neurologic phenotype. Furthermore, there were 10 compound heterozygous patients carrying the p. Ala1003Thr mutation. Among those, 80% having c.2299insC as the second mutation had hepatic phenotype, and all others had neurologic phenotype. We hereby report an association between the c.2299insC mutation and hepatic phenotype and between the p. Ala1003Thr mutation and neurologic phenotype. PMID:25390358

Usta, Julnar; Wehbeh, Antonios; Rida, Khaled; El-Rifai, Omar; Estiphan, Theresa Alicia; Majarian, Tamar; Barada, Kassem

2014-01-01

91

CDK6 associates with the centrosome during mitosis and is mutated in a large Pakistani family with primary microcephaly.  

PubMed

Autosomal recessive primary microcephaly (MCPH) is characterized by reduced head circumference, reduction in the size of the cerebral cortex with otherwise grossly normal brain structure and variable intellectual disability. MCPH is caused by mutations of 11 different genes which code for proteins implicated in cell division and cell cycle regulation. We studied a consanguineous eight-generation family from Pakistan with ten microcephalic children using homozygosity mapping and found a new MCPH locus at HSA 7q21.11-q21.3. Sanger sequencing of the most relevant candidate genes in this region revealed a homozygous single nucleotide substitution c.589G>A in CDK6, which encodes cyclin-dependent kinase 6. The mutation changes a highly conserved alanine at position 197 into threonine (p.Ala197Thr). Post hoc whole-exome sequencing corroborated this mutation's identification as the causal variant. CDK6 is an important protein for the control of the cell cycle and differentiation of various cell types. We show here for the first time that CDK6 associates with the centrosome during mitosis; however, this was not observed in patient fibroblasts. Moreover, the mutant primary fibroblasts exhibited supernumerary centrosomes, disorganized microtubules and mitotic spindles, an increased centrosome nucleus distance, reduced cell proliferation and impaired cell motility and polarity. Upon ectopic expression of the mutant protein and knockdown of CDK6 through shRNA, we noted similar effects. We propose that the identified CDK6 mutation leads to reduced cell proliferation and impairs the correct functioning of the centrosome in microtubule organization and its positioning near the nucleus which are key determinants during neurogenesis. PMID:23918663

Hussain, Muhammad S; Baig, Shahid M; Neumann, Sascha; Peche, Vivek S; Szczepanski, Sandra; Nürnberg, Gudrun; Tariq, Muhammad; Jameel, Muhammad; Khan, Tahir N; Fatima, Ambrin; Malik, Naveed A; Ahmad, Ilyas; Altmüller, Janine; Frommolt, Peter; Thiele, Holger; Höhne, Wolfgang; Yigit, Gökhan; Wollnik, Bernd; Neubauer, Bernd A; Nürnberg, Peter; Noegel, Angelika A

2013-12-20

92

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

PubMed

In genetics, a consanguineous marriage means union between couples who are related as second cousins or closer. The present cross-sectional study was carried out in order to illustrate the prevalence and types of consanguineous marriages in the Shi'a population living in widespread territories in Lebanon including the Bekaa Valley, the south of Lebanon and the southern suburb of Beirut. Data on types of marriages were collected using a simple questionnaire. The total number of couples in the study was 1203. Consanguineous marriage was classified by the degree of relationship between couples. The overall frequency of consanguinity was found to be 28.4%, with first cousin marriages (21.3%) being the most common type followed by first cousins once removed (5.5%), then double first cousins (0.8%). The frequencies of second cousin and beyond second cousin marriages were the same at 0.4% of all the marriages. The mean inbreeding coefficient (?) was estimated at about 0.0161 for the population. There were no significant differences between the three studied territories for frequencies of different types of marriages (p>0.1), nor were there significant differences between the rural and urban areas (p>0.1). PMID:23302154

El-Kheshen, Ghadir; Saadat, Mostafa

2013-09-01

93

Consanguinity: A Risk Factor for Preterm Birth at Less Than 33 Weeks' Gestation  

PubMed Central

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

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

94

Consanguineous Marriages and Their Effects on Common Adult Diseases: Studies from an Endogamous Population  

Microsoft Academic Search

Objectives: The aim of the study was to determine the extent and nature of consanguinity in the Qatari population and its effects on common adult diseases. Subjects and Methods: The study was conducted in urban and semi-urban areas of Qatar between October 2004 and May 2005. The total sample of 1,050 married Qatari females 15 years of age and over

Abdulbari Bener; Rafat Hussain; Ahmad S. Teebi

2007-01-01

95

The influence of admixture and consanguinity on population genetic diversity in Middle East.  

PubMed

The Middle East (ME) is an important crossroad where modern humans migrated 'out of Africa' and spread into Europe and Asia. After the initial peopling and long-term isolation leading to well-differentiated populations, the ME also had a crucial role in subsequent human migrations among Africa, Europe and Asia; thus, recent population admixture has been common in the ME. On the other hand, consanguinity, a well-known practice in the ME, often reduces genetic diversity and works in opposition to admixture. Here, we explored the degree to which admixture and consanguinity jointly affected genetic diversity in ME populations. Genome-wide single-nucleotide polymorphism data were generated in two representative ME populations (Arabian and Iranian), with comparisons made with populations worldwide. Our results revealed an overall higher genetic diversity in both ME populations relative to other non-African populations. We identified a much larger number of long runs of homozygosity in ME populations than in any other populations, which was most likely attributed to high levels of consanguineous marriages that significantly decreased both individual and population heterozygosity. Additionally, we were able to distinguish African, European and Asian ancestries in ME populations and quantify the impact of admixture and consanguinity with statistical approaches. Interestingly, genomic regions with significantly excessive ancestry from individual source populations are functionally enriched in olfactory pathways, which were suspected to be under natural selection. Our findings suggest that genetic admixture, consanguinity and natural selection have collectively shaped the genetic diversity of ME populations, which has important implications in both evolutionary studies and medical practices. PMID:25253659

Yang, Xiong; Al-Bustan, Suzanne; Feng, Qidi; Guo, Wei; Ma, Zhiming; Marafie, Makia; Jacob, Sindhu; Al-Mulla, Fahd; Xu, Shuhua

2014-11-01

96

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

PubMed Central

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

2013-01-01

97

Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course.  

PubMed

Autosomal dominant brachyolmia (Type 3, OMIM #113500) belongs to a group of skeletal dysplasias caused by mutations in the transient receptor potential cation channel, subfamily V, member 4 (TRPV4) gene, encoding a Ca++-permeable, non-selective cation channel. The disorder is characterized by disproportionate short stature with short trunk, scoliosis and platyspondyly. The phenotypic variability and long-term natural course remain inadequately characterized. The purpose of this study was to describe a large Swedish family with brachyolmia type 3 due to a heterozygous TRPV4 mutation c.1847G>A (p.R616Q) in 11 individuals. The mutation has previously been detected in another family with autosomal dominant brachyolmia [Rock et al., 2008]. Review of hospital records and patient assessments indicated that clinical symptoms of brachyolmia became evident by school age with chronic pain in the spine and hips; radiographic changes were evident earlier. Growth was not affected during early childhood but deteriorated with age in some patients due to increasing spinal involvement. Affected individuals had a wide range of subjective symptoms with chronic pain in the extremities and the spine, and paresthesias. Our findings indicate that autosomal dominant brachyolmia may be associated with significant long-term morbidity, as seen in this family. PMID:24677493

Grigelioniene, Giedre; Geiberger, Stefan; Horemuzova, Eva; Moström, Eva; Jäntti, Nina; Neumeyer, Lo; Åström, Eva; Nordenskjöld, Magnus; Nordgren, Ann; Mäkitie, Outi

2014-07-01

98

Novel germline APC gene mutation in a large familial adenomatous polyposis kindred displaying variable phenotypes.  

PubMed Central

The APC gene is mutated in the germline of people from families where there is a predisposition to develop polyposis coli. Many mutations have been described but the relation between their site and the phenotypic expression of the disease remains unclear. The most commonly seen mutation occurs at codon 1309. Many other mutations have been described towards the 5' end of exon 15 of the APC gene but comparatively few have been seen towards the 3' end. Recent reports have indicated the possibility of a functional boundary with respect to severity and age of onset of disease, which lies towards the 5' end of the gene. This report describes a large family whose affected members present with a very variable phenotype ranging from an early onset and severe form to a comparatively mild later onset one. The mutation that predisposes to disease in this family is at a previously undescribed site that lies towards the 3' end of exon 15 of the APC gene, which results in a stop codon. Interestingly, the stop codon is 63 codons downstream of the mutation and therefore may affect the expression of the disease. The addition of this mutation to the growing list of mutations described in the APC gene may provide some insight into the genotype/phenotype relation of the disease thus contributing to the understanding and significance of mutations at specific sites in the APC gene. Images Figure 2 PMID:7797123

Scott, R J; van der Luijt, R; Spycher, M; Mary, J L; Müller, A; Hoppeler, T; Haner, M; Müller, H; Martinoli, S; Brazzola, P L

1995-01-01

99

A Novel SIX3 Mutation Segregates With Holoprosencephaly in a Large Family  

PubMed Central

Holoprosencephaly is the most common structural malformation of the forebrain in humans and has a complex etiology including chromosomal aberrations, single gene mutations and environmental components. Here we present the pertinent clinical findings among members of an unusually large kindred ascertained over 15 years ago following the evaluation and subsequent genetic work-up of a female infant with congenital anomalies. A genome-wide scan and linkage analysis showed only suggestive evidence of linkage to markers on chromosome 2 among the most likely of several pedigree interpretations. We now report that a novel missense mutation in the SIX3 holoprosencephaly gene is the likely cause in this family. Molecular genetic analysis and/or clinical characterization now show that at least 15 members of this family are presumed SIX3 mutation gene carriers, with clinical manifestations ranging from phenotypically normal adults (non-penetrance) to alobar holoprosencephaly incompatible with postnatal life. This particular family represents a seminal example of the variable manifestations of gene mutations in holoprosencephaly and difficulties encountered in their elucidation. PMID:19353631

Solomon, Benjamin D.; Lacbawan, Felicitas; Jain, Mahim; Domene, Sabina; Roessler, Erich; Moore, Cynthia; Dobyns, William B.; Muenke, Maximilian

2009-01-01

100

Analysis of Arabidopsis genome sequence reveals a large new gene family in plants.  

PubMed

A detailed analysis of the currently available Arabidopsis thaliana genomic sequence has revealed the presence of a large number of open reading frames with homology to the stigmatic self-incompatibility (S) genes of Papaver rhoeas. The products of these potential genes are all predicted to be relatively small, basic, secreted proteins with similar predicted secondary structures. We have named these potential genes SPH (S-protein homologues). Their presence appears to have been largely missed by the prediction methods currently used on the genomic sequence. Equivalent homologues could not be detected in the human, microbial, Drosophila or C. elegans genomic databases, suggesting a function specific to plants. Preliminary RT-PCR analysis indicates that at least two members of the family (SPH1, SPH8) are expressed, with expression being greatest in floral tissues. The gene family may total more than 100 members, and its discovery not only illustrates the importance of the genome sequencing efforts, but also indicates the extent of information which remains hidden after the initial trawl for potential genes. PMID:10344198

Ride, J P; Davies, E M; Franklin, F C; Marshall, D F

1999-03-01

101

MTHFR homozygous mutation and additional risk factors for cerebral infarction in a large Italian family.  

PubMed

Several cases with cerebral infarctions associated with the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) have been reported. Given the large number of asymptomatic individuals with the MTHFR mutation, additional risk factors for cerebral infarction should be considered. This study describes a large family with the MTHFR mutation and a combination of heterozygous factor V Leiden mutations and different additional exogenous and endogenous thrombogenic risk factors. Psychomotor retardation and a left fronto-insular infarct associated with the MTHFR mutation together with diminished factor VII and low level of protein C was documented in the first patient. In the second patient, generalized epilepsy and a malacic area in the right nucleus lenticularis was associated with the MTHFR mutation and a low level of protein C. In the third patient, right hemiparesis and a left fronto-temporal porencephalic cyst were documented, together with the MTHFR mutation and hyperhomocysteinemia. An extensive search of additional circumstantial and genetic thrombogenic risk factors should be useful for prophylaxis and prognosis of infants with cerebral infarctions associated with the MTHFR mutation and of their related family members. PMID:19068258

Del Balzo, Francesca; Spalice, Alberto; Perla, Massimo; Properzi, Enrico; Iannetti, Paola

2009-01-01

102

Splice-site mutations in the TRIC gene underlie autosomal recessive nonsyndromic hearing impairment in Pakistani families  

PubMed Central

Hereditary hearing impairment (HI) displays extensive genetic heterogeneity. To date, 67 autosomal recessive nonsyndromic hearing impairment (ARNSHI) loci have been mapped, and 24 genes have been identified. This report describes three large consanguineous ARNSHI Pakistani families, all of which display linkage to marker loci located in the genetic interval of DFNB49 locus on chromosome 5q13. Recently, Riazuddin et al. (Am J Hum Genet 2006; 79:1040–1051) reported that variants within the TRIC gene, which encodes tricellulin, are responsible for HI due to DFNB49. TRIC gene sequencing in these three families led to the identification of a novel mutation (IVS4 + 1G > A) in one family and the discovery of a previously described mutation (IVS4 + 2T > C) in two families. It is estimated that 1.06% (95% confidence interval 0.02–3.06%) of families with ARNSHI in Pakistan manifest HI due to mutations in the TRIC gene. PMID:18084694

Chishti, Muhammad S.; Bhatti, Attya; Tamim, Sana; Lee, Kwanghyuk; McDonald, Merry-Lynn; Leal, Suzanne M.

2009-01-01

103

A large and functionally diverse family of Fad2 genes in safflower (Carthamus tinctorius L.)  

PubMed Central

Background The application and nutritional value of vegetable oil is highly dependent on its fatty acid composition, especially the relative proportion of its two major fatty acids, i.e oleic acid and linoleic acid. Microsomal oleoyl phosphatidylcholine desaturase encoded by FAD2 gene is known to introduce a double bond at the ?12 position of an oleic acid on phosphatidylcholine and convert it to linoleic acid. The known plant FAD2 enzymes are encoded by small gene families consisting of 1-4 members. In addition to the classic oleate ?12-desaturation activity, functional variants of FAD2 that are capable of undertaking additional or alternative acyl modifications have also been reported in a limited number of plant species. In this study, our objective was to identify FAD2 genes from safflower and analyse their differential expression profile and potentially diversified functionality. Results We report here the characterization and functional expression of an exceptionally large FAD2 gene family from safflower, and the temporal and spatial expression profiles of these genes as revealed through Real-Time quantitative PCR. The diversified functionalities of some of the safflower FAD2 gene family members were demonstrated by ectopic expression in yeast and transient expression in Nicotiana benthamiana leaves. CtFAD2-1 and CtFAD2-10 were demonstrated to be oleate desaturases specifically expressed in developing seeds and flower head, respectively, while CtFAD2-2 appears to have relatively low oleate desaturation activity throughout the plant. CtFAD2-5 and CtFAD2-8 are specifically expressed in root tissues, while CtFAD2-3, 4, 6, 7 are mostly expressed in the cotyledons and hypocotyls in young safflower seedlings. CtFAD2-9 was found to encode a novel desaturase operating on C16:1 substrate. CtFAD2-11 is a tri-functional enzyme able to introduce a carbon double bond in either cis or trans configuration, or a carbon triple (acetylenic) bond at the ?12 position. Conclusions In this study, we isolated an unusually large FAD2 gene family with 11 members from safflower. The seed expressed FAD2 oleate ?12 desaturase genes identified in this study will provide candidate targets to manipulate the oleic acid level in safflower seed oil. Further, the divergent FAD2 enzymes with novel functionality could be used to produce rare fatty acids, such as crepenynic acid, in genetically engineered crop plants that are precursors for economically important phytoalexins and oleochemical products. PMID:23289946

2013-01-01

104

Exclusion of LCA5 locus in a consanguineous Turkish family with macular coloboma-type LCA  

Microsoft Academic Search

BackgroundLeber's congenital amaurosis (LCA) is an inherited retinal dystrophy, which causes severe visual impairment in early childhood. Recent molecular genetic studies have linked 11 loci (AIPL1, CRB1, CRX, GUCY2D, RPE65, RDH12, RPGRIP1, TULP1, LCA3, LCA5, and LCA9) to LCA. LCA5 is a new locus, which maps to the 6q11–q16 chromosomal region and was found to be associated with macular coloboma-type

R K Özgül; B Bozkurt; H K?ratl?; A Ö?ü?

2006-01-01

105

[Information should be given on consanguinity as a risk factor for congenital malformations].  

PubMed

In the Born in Bradford study, an increased risk for congenital anomalies was found in the Pakistani subpopulation of Bradford, where cousin marriage is relatively frequent. While consanguinity may be associated with a risk for congenital malformations, it does not prove a causal relationship. Whatever the case, high perinatal mortality as well as the high prevalence of congenital anomalies are good reasons for implementing the knowledge on reproductive risks that has been available for many years. Well-known risk factors include higher maternal age, that was associated with congenital anomalies in the British mothers. Further research in an intervention study may provide more data on whether the associations found are causal. Implementing preconception care should involve primary care physicians, who need both facilities and training. In the Netherlands, the high perinatal mortality, especially in some big cities, could profit from similar interventions. Dutch primary care physicians consider it their responsibility to discuss consanguinity with patients, although there is some reluctance because of anticipated religious and social value conflicts. Without information reaching the target populations, they may lack awareness and will not ask for information themselves. People from Dutch migrant groups would prefer to be informed about reproductive risks of consanguinity by their primary care physicians. PMID:24397975

Cornel, Martina C; Houwink, Elisa J F; Houwink, Pieter E F

2014-01-01

106

Phenotype variability and neonatal diabetes in a large family with heterozygous mutation of the glucokinase gene.  

PubMed

Monogenic diabetes caused by mutations in the glucokinase gene (GCK-MODY) is usually characterized by a mild clinical phenotype. The clinical course of diabetes may be, however, highly variable. The authors present a child with diabetes manifesting with ketoacidosis during the neonatal period, born in a large family with ten members bearing a heterozygous p.Gly223Ser mutation in GCK. DNA sequencing and multiplex ligation-dependent probe amplification were used to confirm GCK mutation and exclude other de novo mutations in other known genes associated with monogenic diabetes. Continuous glucose monitoring (CGM) was used to assess daily glycemic profiles. At the onset of diabetes the child had hyperglycemia 765 mg/dl with pH 7.09. Her glycated hemoglobin level was 8.6% (70.5 mmol/mol). The C-peptide level was below normal range (<0.5 pmol/ml) at onset, and the three- and 6-month follow-up examinations. Current evaluation at age 3 still showed unsatisfactory metabolic control with HbA1c level equal to 8.1% (65.0 mmol/mol). CGM data showed glucose concentrations profile similar to poorly controlled type 1 diabetes. The patient was confirmed to be heterozygous for the p.Gly223Ser mutation and did not show any point mutations or deletions within other monogenic diabetes genes. Other family members with p.Gly223Ser mutation had retained C-peptide levels and mild diabetes manageable with diet (five individuals), oral hypoglycemizing agents (five patients), or insulin (one patient). This mutation was absent within all healthy family members. Heterozygous mutations of the GCK gene may result in neonatal diabetes similar to type 1 diabetes, the cause of such phenotype variety is still unknown. The possibility of other additional, unknown mutations seems to be the most likely explanation for the unusual presentation of GCK-MODY. PMID:21437567

Borowiec, Maciej; Mysliwiec, Malgorzata; Fendler, Wojciech; Antosik, Karolina; Brandt, Agnieszka; Malecki, Maciej; Mlynarski, Wojciech

2011-09-01

107

Recursive characterization of a large family of discrete probability distributions showing extra-Poisson variation  

Microsoft Academic Search

This article analyses the broad family of discrete probability distributions generated by relating Prob (y) to Prob (y?1), …, Prob (y?n), for some n?1, through a recursive equation. This family contains the binomial, negative binomial and Poisson distributions as well as the Katz family of distributions. In addition, the suggested family contains some convolutions of Poisson distributions and other generalized

Alberto Luceño

2005-01-01

108

Genetic and environmental factors affecting bone mineral density in large families.  

PubMed Central

This study assessed whether relatives with low bone mineral density (BMD) could be identified in five large families using historical, biochemical, and genetic markers for osteoporosis. Fifty of 65 relatives had their bone density and bone turnover markers measured, together with an assessment of their risk factors for osteoporosis. Only 33% (5/15) of siblings, 50% (6/12) of children and 43% (10/23) of nephews and nieces had entirely normal BMD. There was no difference in life-style risk factors for osteoporosis, history of previous fractures or body mass index between normal subjects and those with osteopenia or osteoporosis. Osteopenic individuals had a significantly higher than normal osteocalcin value. Within families, there was no clear association between BMD and any of the genetic markers (vitamin D receptor gene polymorphisms, COL 1A1 and COL 1A2 polymorphisms of the collagen gene), either alone or in combination. The addition of genetic markers to the other risk factors for low BMD did not improve the prediction of BMD. In conclusion, we suggest that the presence of osteoporosis in a first degree relative should be one of the clinical indications for bone density measurement as the individuals at risk would not be picked up by other methods. PMID:9799889

Yeap, S. S.; Beaumont, M.; Bennett, A.; Keating, N. A.; White, D. A.; Hosking, D. J.

1998-01-01

109

Functional divergence of the glutathione S-transferase supergene family in Physcomitrella patens reveals complex patterns of large gene family evolution in land plants.  

PubMed

Plant glutathione S-transferases (GSTs) are multifunctional proteins encoded by a large gene family that play major roles in the detoxification of xenobiotics and oxidative stress metabolism. To date, studies on the GST gene family have focused mainly on vascular plants (particularly agricultural plants). In contrast, little information is available on the molecular characteristics of this large gene family in nonvascular plants. In addition, the evolutionary patterns of this family in land plants remain unclear. In this study, we identified 37 GST genes from the whole genome of the moss Physcomitrella patens, a nonvascular representative of early land plants. The 37 P. patens GSTs were divided into 10 classes, including two new classes (hemerythrin and iota). However, no tau GSTs were identified, which represent the largest class among vascular plants. P. patens GST gene family members showed extensive functional divergence in their gene structures, gene expression responses to abiotic stressors, enzymatic characteristics, and the subcellular locations of the encoded proteins. A joint phylogenetic analysis of GSTs from P. patens and other higher vascular plants showed that different class GSTs had distinct duplication patterns during the evolution of land plants. By examining multiple characteristics, this study revealed complex patterns of evolutionary divergence among the GST gene family in land plants. PMID:23188805

Liu, Yan-Jing; Han, Xue-Min; Ren, Lin-Ling; Yang, Hai-Ling; Zeng, Qing-Yin

2013-02-01

110

Moxidectin and the avermectins: Consanguinity but not identity  

PubMed Central

The avermectins and milbemycins contain a common macrocyclic lactone (ML) ring, but are fermentation products of different organisms. The principal structural difference is that avermectins have sugar groups at C13 of the macrocyclic ring, whereas the milbemycins are protonated at C13. Moxidectin (MOX), belonging to the milbemycin family, has other differences, including a methoxime at C23. The avermectins and MOX have broad-spectrum activity against nematodes and arthropods. They have similar but not identical, spectral ranges of activity and some avermectins and MOX have diverse formulations for great user flexibility. The longer half-life of MOX and its safety profile, allow MOX to be used in long-acting formulations. Some important differences between MOX and avermectins in interaction with various invertebrate ligand-gated ion channels are known and could be the basis of different efficacy and safety profiles. Modelling of IVM interaction with glutamate-gated ion channels suggest different interactions will occur with MOX. Similarly, profound differences between MOX and the avermectins are seen in interactions with ABC transporters in mammals and nematodes. These differences are important for pharmacokinetics, toxicity in animals with defective transporter expression, and probable mechanisms of resistance. Resistance to the avermectins has become widespread in parasites of some hosts and MOX resistance also exists and is increasing. There is some degree of cross-resistance between the avermectins and MOX, but avermectin resistance and MOX resistance are not identical. In many cases when resistance to avermectins is noticed, MOX produces a higher efficacy and quite often is fully effective at recommended dose rates. These similarities and differences should be appreciated for optimal decisions about parasite control, delaying, managing or reversing resistances, and also for appropriate anthelmintic combination. PMID:24533275

Prichard, Roger; Menez, Cecile; Lespine, Anne

2012-01-01

111

Family Strengthening Writ Large: On becoming a Nation that Promotes Strong Families and Successful Youth. Policy Brief No. 24  

ERIC Educational Resources Information Center

Culture and systemic change are paramount to achieving significant and long-lasting gains in child and youth wellbeing and, in time, securing the future of our nation. This brief, based on a high-level synthesis of eight years of experience and research in place-based family strengthening, makes the case for a national transformation to a society…

Online Submission, 2007

2007-01-01

112

Application of a high-throughput genotyping method for loci exclusion in non-consanguineous Australian pedigrees with autosomal recessive retinitis pigmentosa  

PubMed Central

Purpose Retinitis pigmentosa (RP) is the most common form of inherited blindness, caused by progressive degeneration of photoreceptor cells in the retina, and affects approximately 1 in 3,000 people. Over the past decade, significant progress has been made in gene therapy for RP and related diseases, making genetic characterization increasingly important. Recently, high-throughput technologies have provided an option for reasonably fast, cost-effective genetic characterization of autosomal recessive RP (arRP). The current study used a single nucleotide polymorphism (SNP) genotyping method to exclude up to 28 possible disease-causing genes in 31 non-consanguineous Australian families affected by arRP. Methods DNA samples were collected from 59 individuals affected with arRP and 74 unaffected family members from 31 Australian families. Five to six SNPs were genotyped for 28 genes known to cause arRP or the related disease Leber congenital amaurosis (LCA). Cosegregation analyses were used to exclude possible causative genes from each of the 31 families. Bidirectional sequencing was used to identify disease-causing mutations in prioritized genes that were not excluded with cosegregation analyses. Results Two families were excluded from analysis due to identification of false paternity. An average of 28.9% of genes were excluded per family when only one affected individual was available, in contrast to an average of 71.4% or 89.8% of genes when either two, or three or more affected individuals were analyzed, respectively. A statistically significant relationship between the proportion of genes excluded and the number of affected individuals analyzed was identified using a multivariate regression model (p<0.0001). Subsequent DNA sequencing resulted in identification of the likely disease-causing gene as CRB1 in one family (c.2548 G>A) and USH2A in two families (c.2276 G>T). Conclusions This study has shown that SNP genotyping cosegregation analysis can be successfully used to refine and expedite the genetic characterization of arRP in a non-consanguineous population; however, this method is effective only when DNA samples are available from more than one affected individual. PMID:22876132

Paterson, Rachel L.; McLaren, Terri L.; Hewitt, Alex W.; Hoffmann, Ling; Lamey, Tina M.

2012-01-01

113

Large BRCA1 and BRCA2 genomic rearrangements in Malaysian high risk breast-ovarian cancer families.  

PubMed

Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2. PMID:20617377

Kang, Peter; Mariapun, Shivaani; Phuah, Sze Yee; Lim, Linda Shushan; Liu, Jianjun; Yoon, Sook-Yee; Thong, Meow Keong; Mohd Taib, Nur Aishah; Yip, Cheng Har; Teo, Soo-Hwang

2010-11-01

114

Large, rapidly evolving intergenic spacers in the mitochondrial DNA of the salamander family Ambystomatidae (Amphibia: Caudata).  

PubMed

We report the presence, in the mitochondrial DNA (mtDNA) of all of the sexual species of the salamander family Ambystomatidae, of a shared 240-bp intergenic spacer between tRNAThr and tRNAPro. We place the intergenic spacer in context by presenting the sequence of 1,746 bp of mtDNA from Ambystoma tigrinum tigrinum, describe the nucleotide composition of the intergenic spacer in all of the species of Ambystomatidae, and compare it to other coding and noncoding regions of Ambystoma and several other vertebrate mtDNAs. The nucleotide substitution rate of the intergenic spacer is approximately three times faster than the substitution rate of the control region, as shown by comparisons among six Ambystoma macrodactylum sequences and eight members of the Ambystoma tigrinum complex. We also found additional inserts within the intergenic spacers of five species that varied from 87-444 bp in length. The presence of the intergenic spacer in all sexual species of Ambystomatidae suggests that it arose at least 20 MYA and has been a stable component of the ambystomatid mtDNA ever since. As such, it represents one of the few examples of a large and persistent intergenic spacer in the mtDNA of any vertebrate clade. PMID:9364774

McKnight, M L; Shaffer, H B

1997-11-01

115

Scoliosis, blindness and arachnodactyly in a large Turkish family: is it a new syndrome?  

PubMed

In this report we have described an affected sib in a large Turkish family who appears to have a new distinct dominantly-inherited blindness, scoliosis and arachnodactyly syndrome. The combination of clinical abnormalities in these patients did not initially suggest Marfan syndrome or other connective tissue disorders associated with ectopia lentis. The proband was a 16-year-old boy who was referred to our clinics for scoliosis. He had arachnodactyly of both fingers and toes. He had been suffering from progressive visual loss and strabismus since he was eight-years-old. His 20-year-old brother had severe kyphoscoliosis, and arachnodactyly of fingers and toes. He was 130 cm tall and was bilaterally blind. His 23-year-old sister had only eye findings but no arachnodactyly or scoliosis. His 60-year-old father had mild scoliosis, blindness and arachnodactyly and mother was normal. We performed routine mutation analyses in the genes FBN1, TGFBR1 and TGFBR2, but no mutation has been detected. Our Turkish patients are most likely affected by a hitherto unrecorded condition which is caused by an autosomal dominant gene defect with variable expression but we can not exclude multigenic inheritance. Further studies are needed to assess the contribution of sex influence to the syndrome because the female relative is less affected. PMID:18990988

Dundar, M; Erkilic, K; Argun, M; Caglayan, A O; Comeglio, P; Koseoglu, E; Matyas, G; Child, A H

2008-01-01

116

Atrial fibrillation anticoagulation care in a large urban family medicine practice  

PubMed Central

Abstract Objective To determine the proportion of patients with atrial fibrillation (AF) in primary care achieving guideline-concordant stroke prevention treatment based on both the previous (2010) and the updated (2012) Canadian guideline recommendations. Design Retrospective chart review. Participants Primary care patients (N = 204) with AF. The mean age was 71.3 years and 53.4% were women. Setting Large urban community family practice in Toronto, Ont. Main outcome measures Patient demographic characteristics such as sex and age; a list of current cardiac medications including anticoagulants and antiplatelets; the total number of medications; relevant current and past medical history including presence of diabetes, stroke or transient ischemic attack, hypertension, and vascular disease; number of visits to the family physician and cardiologist in the past year and past 5 years, and how many of these were for AF; the number of visits to the emergency department or hospitalizations for AF, congestive heart failure, or stroke; if patients were taking warfarin, how often their international normalized ratios were recorded, and how many times they were in the reference range; CHADS2 (congestive heart failure, hypertension, age ? 75, diabetes mellitus, and stroke or transient ischemic attack) score, if recorded; and reason for not taking oral anticoagulants when they should have been, if recorded. Results Among those who had CHADS2 scores of 0, 64 patients (97.0%) were receiving appropriate stroke prevention in AF (SPAF) treatment according to the 2010 guidelines. When the 2012 guidelines were applied, 39 patients (59.1%) were receiving appropriate SPAF treatment (P < .001). For those with CHADS2 scores of 1, 88.4% of patients had appropriate SPAF treatment according to the 2010 guidelines, but only 55.1% were adequately treated according to the 2012 guidelines (P < .001). Of the patients at the highest risk (CHADS2 score > 1), 68.1% were adequately treated with anticoagulation and an additional 8.7% (6 of 69) had documented reasons why they were not taking anticoagulants. Conclusion When assessed using the 2012 Canadian Cardiovascular Society AF guidelines, the proportion of patients receiving appropriate SPAF therapy in this primary care setting decreased substantially. All patients with CHADS2 scores of 0 or 1 should be reassessed to ensure that they are receiving optimal stroke prevention treatment. PMID:24627401

Valentinis, Alissia; Ivers, Noah; Bhatia, Sacha; Meshkat, Nazanin; Leblanc, Kori; Ha, Andrew; Morra, Dante

2014-01-01

117

Whole Exome Sequencing Identifies a Causal RBM20 Mutation in a Large Pedigree with Familial Dilated Cardiomyopathy  

PubMed Central

Background Whole exome sequencing (WES) is a powerful technique for Mendelian disease gene discovery. However, variant prioritization remains a challenge. We applied WES to identify the causal variant in a large family with familial dilated cardiomyopathy (DMC) of unknown etiology. Methods and Results A large family with autosomal dominant, familial DCM was identified. Exome capture and sequencing was performed in 3 remotely related, affected subjects predicted to share <0.1% of their genomes by descent. Shared variants were filtered for rarity, evolutionary conservation, and predicted functional significance, and remaining variants were filtered against 71 locally generated exomes. Variants were also prioritized using the Variant Annotation Analysis and Search Tool (VAAST). Final candidates were validated by Sanger sequencing and tested for segregation. There were 664 shared heterozygous nonsense, missense, or splice site variants, of which 26 were rare (minor allele frequency ? 0.001 or not reported) in two public databases. Filtering against internal exomes reduced the number of candidates to 2, and of these, a single variant (c.1907 G>A) in RBM20, segregated with disease status and was absent in unaffected internal reference exomes. Bioinformatic prioritization with VAAST supported this result. Conclusions WES of remotely related DCM subjects from a large, multiplex family, followed by systematic filtering, identified a causal RBM20 mutation without the need for linkage analysis. PMID:23861363

Wells, Quinn S.; Becker, Jason R.; Su, Yan R.; Mosley, Jonathan D.; Weeke, Peter; D'Aoust, Laura; Ausborn, Natalie L.; Ramirez, Andrea H.; Pfotenhauer, Jean P.; Naftilan, Allen J.; Markham, Larry; Exil, Vernat; Roden, Dan M.; Hong, Charles C.

2013-01-01

118

Family Dinner and Disordered Eating Behaviors in a Large Cohort of Adolescents  

Microsoft Academic Search

We aimed to examine longitudinal associations between family dinner and disordered eating behaviors among adolescents. We studied 7535 females and 5913 males, 9 to 14 years of age in 1996. We performed multivariable logistic regression to assess the associations of previous year family dinner with 1-year incidence of each of 3 outcomes: purging, binge eating, and frequent dieting. Compared to

Jess Haines; Matthew W. Gillman; Sheryl Rifas-Shiman; Alison E. Field; S. Bryn Austin

2009-01-01

119

Genealogy, natural history, and phenotype of Alstrom syndrome in a large Acadian kindred and three additional families  

Microsoft Academic Search

We describe a large Acadian kindred including 8 Alstrom Syndrome (AS) patients, with an age range of 4 to 26 at the time of clinical assessment. The affected subjects come from 5 nuclear families within this kindred. The phenotype includes early childhood retinopathy, progressive sensorineural hearing loss, truncal obesity, and acanthosis nigricans. In addition, hyperinsulinemia and hypertriglyceridemia with normal cholesterol

Jan D. Marshall; Mark D. Ludman; Sarah E. Shea; Sonia R. Salisbury; Steven M. Willi; Robert G. LaRoche; Patsy M. Nishina

1997-01-01

120

Spectrum of SPG4 Mutations in a Large Collection of North American Families With Hereditary Spastic Paraplegia  

Microsoft Academic Search

Background: Hereditary spastic paraplegia (HSP) is a neu- rodegenerative disease characterized by progressive spas- ticity and weakness of the lower limbs. The most com- mon form of HSP is caused by mutations in the SPG4 gene, which codes for spastin, an adenosine triphosphatase with various cellular activities (AAA) protein family member. Objective: To investigate a large collection of predomi- nantly

Inge A. Meijer; Collette K. Hand; P. Cossette; Denise A. Figlewicz; Guy A. Rouleau

2002-01-01

121

Characterization of the p16 gene in the mouse: Evidence for a large gene family  

SciTech Connect

The p16 gene product is an inhibitor of the cyclin-dependent kinase 4 (CDK4)/cyclin D complex. When uninhibited, the CDK4/cyclin D complex participates in the phosphorylation of the retinoblastoma (RB) protein and renders it inactive. Upon inactivation of the RB protein, transition from the G{sub 1} to the S phase of mitosis occurs and results in cellular proliferation. Thus, p16 is presumed to act as a negative regulator of cell growth by preventing the phosphorylation, and thereby subsequent inactivation, of RB by CDK4/cyclin D. Recently, the p16 gene (also known as the multiple tumor suppressor 1 (MTS1) gene) has been mapped to chromosome 9p21 and found to be deleted or mutated in a number of tumor cell lines. These findings support the role of p16 as a growth inhibitor or tumor suppressor gene and suggest that the mutation of this gene may have global implications in carcinogenesis. We have chosen to test the functional significance of p16 mutations in vivo through the generation of a mouse mutant for p16. In preparation for this undertaking, eight apparently independent (as judged by restriction enzyme digestion and differential hybridization) mouse genomic embryonic stem cell clones have been identified using exon 2 from the human p16 gene as a probe. The identification of these multiple nonoverlapping clones was not entirely surprising since the reduced stringency hybridization of a zoo blot with the same probe also revealed 10-15 positive EcoRI fragments in all species tested, including human, monkey, cow, dog, cat, rabbit, hamster, mouse, chicken and D. melanogaster. Taken together, these findings suggest that the p16 gene is a member of a large gene family. The location of these genomic clones, as well as their potential expression in the mouse, is currently under investigation.

Fountain, J.W.; Giendening, J.M.; Flores, J.F. [Univ. of Southern California, Los Angeles, CA (United States)] [and others

1994-09-01

122

Identification of MYOC gene mutation and polymorphism in a large Malay family with juvenile-onset open angle glaucoma  

PubMed Central

Purpose To screen for mutations in the coding region of the myocilin (MYOC) gene in a large Malay family with juvenile-onset open angle glaucoma (JOAG). Methods A total of 122 family members were thoroughly examined and screened for JOAG. Venipuncture was conducted. Genomic DNA was extracted from peripheral blood leukocytes. The presence of a mutation and a polymorphism was ascertained with PCR amplification followed by the direct sequencing technique. Results Thirty-two of the 122 screened family members were identified to have JOAG (11 new cases and 21 known cases). An autosomal dominant inheritance pattern with incomplete penetrance was observed. A C?A substitution at position 1440 in exon 3 that changes asparagine (AAC) to lysine (AAA) was identified in affected family members except two probands (III:5 and IV:6). Six probands were identified as having the Asn480Lys mutation but have not developed the disease yet. An intronic polymorphism IVS2 730 +35 G>A was also identified. There was a significant association between Asn480Lys (p<0.001) and IVS2 730+35G>A (p<0.001) in the affected and unaffected probands in this family. Conclusions The Asn480Lys mutation and the IVS2 730+35 G>A polymorphism increased susceptibility to JOAG in this large Malay pedigree. Identifying the MYOC mutations and polymorphisms is important for providing presymptomatic molecular diagnosis. PMID:24883016

Mimiwati, Z; Nurliza, K; Marini, M; Liza-Sharmini, AT

2014-01-01

123

Reconstruction of Oomycete Genome Evolution Identifies Differences in Evolutionary Trajectories Leading to Present-Day Large Gene Families  

PubMed Central

The taxonomic class of oomycetes contains numerous pathogens of plants and animals but is related to nonpathogenic diatoms and brown algae. Oomycetes have flexible genomes comprising large gene families that play roles in pathogenicity. The evolutionary processes that shaped the gene content have not yet been studied by applying systematic tree reconciliation of the phylome of these species. We analyzed evolutionary dynamics of ten Stramenopiles. Gene gains, duplications, and losses were inferred by tree reconciliation of 18,459 gene trees constituting the phylome with a highly supported species phylogeny. We reconstructed a strikingly large last common ancestor of the Stramenopiles that contained ?10,000 genes. Throughout evolution, the genomes of pathogenic oomycetes have constantly gained and lost genes, though gene gains through duplications outnumber the losses. The branch leading to the plant pathogenic Phytophthora genus was identified as a major transition point characterized by increased frequency of duplication events that has likely driven the speciation within this genus. Large gene families encoding different classes of enzymes associated with pathogenicity such as glycoside hydrolases are formed by complex and distinct patterns of duplications and losses leading to their expansion in extant oomycetes. This study unveils the large-scale evolutionary dynamics that shaped the genomes of pathogenic oomycetes. By the application of phylogenetic based analyses methods, it provides additional insights that shed light on the complex history of oomycete genome evolution and the emergence of large gene families characteristic for this important class of pathogens. PMID:22230142

Seidl, Michael F.; Van den Ackerveken, Guido; Govers, Francine; Snel, Berend

2012-01-01

124

Familial clustering of Langerhans cell histiocytosis.  

PubMed

Langerhans cell histiocytosis (LCH) is considered a non-hereditary disorder. Evaluation of the few familial cases might provide insight into its aetiology and pathogenesis. We conducted a survey to identify familial LCH cases. Data on family history, zygosity assessment in twins, clinical and laboratory features, treatment outcome, and present status were collected. According to variable confidence for twins monozygosity assessment, we termed these pairs 'presumed monozygotic' (pMZ). Nine families had more than one affected relative: five with LCH-concordant twin pairs, four with LCH in siblings or cousins. Three twin pairs not concordant for LCH were also studied. Overall, four of five pMZ twin pairs and one of three dizygotic (DZ) pairs were concordant for LCH. The pMZ twins had simultaneous and early disease onset (mean age 5.4 months); onset was at 21 months in the DZ pair. Clinical features were similar in the pMZ pairs. One pair of DZ twins had disseminated LCH. The three healthy twins (one pMZ, two DZ) remain asymptomatic 0.3, 5.9 and 4.7 years, respectively, after disease onset in their co-twins. Of the two families with affected non-twin siblings, one had known parental consanguinity and the other possible consanguinity. Potential consanguinity was also present in one of the two families with affected first cousins. Our data support high LCH concordance rates in pMZ twins and add the finding of LCH concordance in one of three dizygotic pairs studied. Taken together with our identification of LCH in siblings and first cousins from known or possibly consanguineous families, and with prior reports of three affected parent-child pairs, the data support a role for genetic factor(s) in LCH. The work-up of newly diagnosed patients should include a careful, extensive family history and chromosome studies. When possible, constitutional and/or lesional DNA should be obtained for future study. PMID:10606898

Aricò, M; Nichols, K; Whitlock, J A; Arceci, R; Haupt, R; Mittler, U; Kühne, T; Lombardi, A; Ishii, E; Egeler, R M; Danesino, C

1999-12-01

125

Whole-proteome phylogeny of large dsDNA virus families by an alignment-free method  

PubMed Central

The vast sequence divergence among different virus groups has presented a great challenge to alignment-based sequence comparison among different virus families. Using an alignment-free comparison method, we construct the whole-proteome phylogeny for a population of viruses from 11 viral families comprising 142 large dsDNA eukaryote viruses. The method is based on the feature frequency profiles (FFP), where the length of the feature (l-mer) is selected to be optimal for phylogenomic inference. We observe that (i) the FFP phylogeny segregates the population into clades, the membership of each has remarkable agreement with current classification by the International Committee on the Taxonomy of Viruses, with one exception that the mimivirus joins the phycodnavirus family; (ii) the FFP tree detects potential evolutionary relationships among some viral families; (iii) the relative position of the 3 herpesvirus subfamilies in the FFP tree differs from gene alignment-based analysis; (iv) the FFP tree suggests the taxonomic positions of certain “unclassified” viruses; and (v) the FFP method identifies candidates for horizontal gene transfer between virus families. PMID:19553209

Wu, Guohong Albert; Jun, Se-Ran; Sims, Gregory E.; Kim, Sung-Hou

2009-01-01

126

Between Acculturation and Ambivalence: Knowledge of Genetics and Attitudes towards Genetic Testing in a Consanguineous Bedouin Community  

Microsoft Academic Search

The Bedouins of the Negev (Southern part of Israel) are a community at increased risk for genetic diseases and congenital anomalies as a result of frequent consanguinity (particularly patrilateral parallel-cousin marriage) and underutilization of prenatal genetic tests due to a Muslim ban on abortion. Objective: To assess the knowledge and attitudes of Bedouin schoolchildren and their teachers towards a community-based,

Aviad E. Raz; Marcela Atar; Maya Rodnay; Ilana Shoham-Vardi; Rivka Carmi

2003-01-01

127

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

PubMed

Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder, incompatible with life. It is characterized by enlarged polycystic kidneys and post axial polydactyly. Foetal or neonatal death is caused by pulmonary hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed for her current pregnancy at 18 weeks of gestation showed features consistent with MKS. The termination of pregnancy was declined and a live newborn female was delivered via an emergency caeserean section at 34 weeks of gestation due to previous history of lower segment caesarean section (LSCS) & leaking. Physical examination of the neonate confirmed the features of MKS. The neonate died within 4-5 hours of birth. This case represented a second trimester diagnosis of a recurrent case of MKS in a non-consanguineous marriage. PMID:24353549

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

2013-01-01

128

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

PubMed Central

Meckel-Gruber Syndrome (MKS) is a rare, autosomal recessive genetic disorder, incompatible with life. It is characterized by enlarged polycystic kidneys and post axial polydactyly. Foetal or neonatal death is caused by pulmonary hypoplasia. We report a case of a 35 year old woman who presented at 7 weeks of gestation of her sixth pregnancy. A transabdominal anomaly ultrasound performed for her current pregnancy at 18 weeks of gestation showed features consistent with MKS. The termination of pregnancy was declined and a live newborn female was delivered via an emergency caeserean section at 34 weeks of gestation due to previous history of lower segment caesarean section (LSCS) & leaking. Physical examination of the neonate confirmed the features of MKS. The neonate died within 4-5 hours of birth. This case represented a second trimester diagnosis of a recurrent case of MKS in a non-consanguineous marriage. PMID:24353549

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

2013-01-01

129

A novel RUNX2 missense mutation predicted to disrupt DNA binding causes cleidocranial dysplasia in a large Chinese family with hyperplastic nails  

Microsoft Academic Search

BACKGROUND: Cleidocranial dysplasia (CCD) is a dominantly inherited disease characterized by hypoplastic or absent clavicles, large fontanels, dental dysplasia, and delayed skeletal development. The purpose of this study is to investigate the genetic basis of Chinese family with CCD. METHODS: Here, a large Chinese family with CCD and hyperplastic nails was recruited. The clinical features displayed a significant intrafamilial variation.

Shaohua Tang; Qiyu Xu; Xueqin Xu; Jicheng Du; Xuemei Yang; Yusheng Jiang; Xiaoqin Wang; Nancy Speck; Taosheng Huang

2007-01-01

130

Combining family- and population-based imputation data for association analysis of rare and common variants in large pedigrees.  

PubMed

In the last two decades, complex traits have become the main focus of genetic studies. The hypothesis that both rare and common variants are associated with complex traits is increasingly being discussed. Family-based association studies using relatively large pedigrees are suitable for both rare and common variant identification. Because of the high cost of sequencing technologies, imputation methods are important for increasing the amount of information at low cost. A recent family-based imputation method, Genotype Imputation Given Inheritance (GIGI), is able to handle large pedigrees and accurately impute rare variants, but does less well for common variants where population-based methods perform better. Here, we propose a flexible approach to combine imputation data from both family- and population-based methods. We also extend the Sequence Kernel Association Test for Rare and Common variants (SKAT-RC), originally proposed for data from unrelated subjects, to family data in order to make use of such imputed data. We call this extension "famSKAT-RC." We compare the performance of famSKAT-RC and several other existing burden and kernel association tests. In simulated pedigree sequence data, our results show an increase of imputation accuracy from use of our combining approach. Also, they show an increase of power of the association tests with this approach over the use of either family- or population-based imputation methods alone, in the context of rare and common variants. Moreover, our results show better performance of famSKAT-RC compared to the other considered tests, in most scenarios investigated here. PMID:25132070

Saad, Mohamad; Wijsman, Ellen M

2014-11-01

131

ORIGINAL ARTICLE Familial steroid-sensitive nephrotic syndrome  

E-print Network

ORIGINAL ARTICLE Familial steroid-sensitive nephrotic syndrome in Southern Israel: clinical January 2007 # IPNA 2007 Abstract Reports on genetically informative steroid-re- sponsive (sensitive with a high rate of consanguinity. The clinical presentation and steroid response of its 11 affected

Friedman, Nir

132

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

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.

Weiss, S.; Korostishevsky, M. [Sackler Faculty of Medicine, Ramat-Aviv (Israel); Frydman, M. [Haim Sheba Medical Center, Tel-Hashomer (Israel)] [and others

1994-09-01

133

Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis.  

PubMed

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet. We undertook exome sequencing of 3 distantly related affected individuals. Bioinformatics filtering revealed a known pathogenic missense mutation c.188G>A (p.Arg63His) in TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders. PMID:25337069

Daly, Sarah B; Shah, Hitesh; O'Sullivan, James; Anderson, Beverley; Bhaskar, Sanjeev; Williams, Simon; Al-Sheqaih, Nada; Mueed Bidchol, Abdul; Banka, Siddharth; Newman, William G; Girisha, Katta M

2014-08-01

134

Exome Sequencing Identifies a Dominant TNNT3 Mutation in a Large Family with Distal Arthrogryposis  

PubMed Central

Distal arthrogryposis (DA) is a group of rare, clinically and genetically heterogeneous disorders primarily characterized by congenital contractures of the distal limb joints without a neuromuscular disease. Mutations in at least 8 different genes have been shown to cause DA. Here, we report a 4-generation Indian family with 18 affected members presenting variable features of camptodactyly, brachydactyly, syndactyly, decreased flexion palmar creases, ulnar deviation of the hands, sandal gaps and club feet. We undertook exome sequencing of 3 distantly related affected individuals. Bioinformatics filtering revealed a known pathogenic missense mutation c.188G>A (p.Arg63His) in TNNT3 in all 3 affected individuals that segregated with the phenotype. The affected individuals exhibit significant phenotypic variability. This study demonstrates the value of exome sequencing helping to define the causative variant in genetically heterogeneous disorders. PMID:25337069

Daly, Sarah B.; Shah, Hitesh; O'Sullivan, James; Anderson, Beverley; Bhaskar, Sanjeev; Williams, Simon; Al-Sheqaih, Nada; Mueed Bidchol, Abdul; Banka, Siddharth; Newman, William G.; Girisha, Katta M.

2014-01-01

135

Large Lepton-flavor Mixings from E8 Kodaira Singularity: Lopsided Texture via F-theory Family Unification  

E-print Network

We show that a special type of colliding 7-brane configuration of a codimension-two singularity realizes not only a six-dimensional spectrum with exactly the same quantum numbers as that of the three-generation E7/(SU(5) x U(1)^3) coset family unification model, but also the three sets of nonchiral singlet pairs with precisely the correct U(1) charges needed for explaining the Yukawa hierarchies and large lepton-flavor mixings in a well-known seesaw scenario.

Mizoguchi, Shun'ya

2014-01-01

136

Familial aggregation of melanoma risks in a large population-based sample of melanoma cases  

Microsoft Academic Search

ObjectiveMelanoma has been shown in numerous studies to be associated with sun exposure, and with host phenotypic factors of genetic origin. In this study we use information from a large series of incident cases of melanoma from an international population-based study to examine the patterns of incidence of melanoma in the first-degree relatives of these cases. Methods: A total of

Colin B. Begg; Amanda Hummer; Urvi Mujumdar; Bruce K. Armstrong; Anne Kricker; Loraine D. Marrett; Robert C. Millikan; Stephen B. Gruber; Hoda Anton-Culver; Judith B. Klotz; Roberto Zanetti; Richard P. Gallagher; Terence Dwyer; Timothy R. Rebbeck; Marrianne R. Berwick

2004-01-01

137

Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm  

PubMed Central

SUMMARY Izumo, a sperm membrane protein, is essential for gamete fusion in the mouse. It has an Ig (Immunoglobulin) domain and an N-terminal domain for which neither the functions nor homologous sequences are known. In the present work we identified three novel proteins showing an N-terminal domain with significant homology to the N-terminal domain of Izumo. We named this region "Izumo domain", and the novel proteins “Izumo 2”,”Izumo 3” and “Izumo 4”, retaining “Izumo 1” for the first described member of the family. Izumo 1, 2 and 3 are transmembrane proteins expressed specifically in the testis, and Izumo 4 is a soluble protein expressed in the testis and in other tissues. Electrophoresis under mildly denaturing conditions, followed by Western blot analysis, showed that Izumo 1, 3 and 4 formed protein complexes on sperm, Izumo 1 forming several larger complexes and Izumo 3 and 4 forming a single larger complex. Studies using different recombinant Izumo constructs suggested the Izumo domain possesses the ability to form dimers, whereas the transmembrane domain or the cytoplasmic domain or both of Izumo 1 are required for the formation of multimers of higher order. Co-immunoprecipitation studies showed the presence of other sperm proteins associated with Izumo-1, suggesting Izumo 1 forms a multi-protein membrane complex. Our results raise the possibility that Izumo 1 might be involved in organizing or stabilizing a multi-protein complex essential for the function of the membrane fusion machinery. PMID:19658160

Ellerman, Diego A; Pei, Jimin; Gupta, Surabhi; Snell, William J; Myles, Diana; Primakoff, Paul

2013-01-01

138

Rhodopsin F45L Allele Does Not Cause Autosomal Dominant Retinitis Pigmentosa in a Large Caucasian Family  

PubMed Central

Purpose To ascertain the potential pathogenicity of a retinitis pigmentosa (RP)-causing RHO F45L allele in a family affected by congenital achromatopsia (ACHM). Methods Case series/observational study that included two patients with ACHM and 24 extended family members. Molecular genetic analysis was performed to identify RHO F45L carrier status in the family and a control population. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to image the photoreceptor mosaic and assess rod and cone structure. Spectral domain optical coherence tomography (SD-OCT) was used to examine retinal lamination. Comprehensive clinical testing included acuity, color vision, and dilated fundus examination. Electroretinography was used to assess rod and cone function. Results Five carriers of the RHO F45L allele alone (24–80 years) and three carriers in combination with a heterozygous CNGA3 mutant allele (10–64 years) were all free of the classic symptoms and signs of RP. In heterozygous carriers of both mutations, SD-OCT showed normal retinal thickness and intact outer retinal layers; rod and cone densities were within normal limits on AOSLO. The phenotype in two individuals affected with ACHM and harboring the RHO F45L allele was indistinguishable from that previously reported for ACHM. Conclusions The RHO F45L allele is not pathogenic in this large family; hence, the two ACHM patients would unlikely develop RP in the future. Translational Relevance The combined approach of comprehensive molecular analysis of individual genomes and noninvasive cellular resolution retinal imaging enhances the current repertoire of clinical diagnostic tools, giving a substantial impetus to personalized medicine. PMID:24049715

Vincent, Andrea L.; Carroll, Joseph; Fishman, Gerald A.; Sauer, Alexandra; Sharp, Dianne; Summerfelt, Phyllis; Williams, Vesper; Dubis, Adam M.; Kohl, Susanne; Wong, Fulton

2013-01-01

139

Atypical 18p- syndrome associated with partial trisomy 16p in a chromosomally unbalanced child of consanguineous parents with an identical balanced translocation.  

PubMed

A 2 month old male infant was found to have mild growth retardation, prominent forehead, low set ears, low nasal bridge, rounded facies, cleft palate, webbed neck, shawl scrotum, and absent right kidney. The propositus, a product of a consanguineous marriage, had extremely rare abnormal cytogenetic findings. His karyotype contained three derivative chromosomes that originated from a familial translocation, t(16;18)(p13.3;p11.2) carried by both parents. Based on parental studies, the infant's unbalanced karyotype was defined as: [46,XY,t(16;18)(p13.3;p11.2), der(18)t(16;18).ish t(16;18)(16ptel-,16qtel+,18ptel+,wcp16+,wcp18+;16ptel+,18ptel-,wcp16+,wcp18+), der(18)t(16;18)(16ptel+,18ptel-,wcp16+,wcp18+)]. We describe this child at 2 months of age with a follow up at 4 1/2 years, exhibiting a mixed clinical picture with features of both 18p- and partial trisomy 16p13.3. PMID:15953407

Kupchik, Gabriel S; Barrett, Shannon K; Babu, Arvind; Charria-Ortiz, Gustavo; Velinov, Milen; Macera, Michael J

2005-01-01

140

Molecular and neurological characterizations of three Saudi families with lipoid proteinosis  

PubMed Central

Background Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood. It is caused by homozygous or compound heterozygous mutations in the ECM1 gene. The disease is largely uncharacterized in Arab population and the mutation(s) spectrum in the Arab population is largely unknown. We report the neurologic and neuroradiologic characteristics and ECM1 gene mutations of seven individuals with lipoid proteinosis (LP) from three unrelated consanguineous families. Methods Clinical, neurologic, and neuro-ophthalmologic examinations; skin histopathology; brain CT and MRI; and sequencing of the fullECM1 gene. Results All seven affected individuals had skin scarring and hoarseness from early childhood. The two children in Family 1 had worse skin involvement and worse hoarseness than affected children of Families 2 and 3. Both children in Family 1 were modestly mentally retarded, and one had typical calcifications of the amygdalae on CT scan. Affected individuals in Families 2 and 3 had no grossneurologic, neurodevelopmental, or neuroimaging abnormalities. Skin histopathology was compatible with LP in all three families. Sequencing the full coding region of ECM1 gene revealed two novel mutationsin Family 1 (c.1300-1301delAA) and Family 2 (p.Cys269Tyr) and in Family 3 a previously described 1163 bp deletion starting 34 bp into intron 8. Conclusions These individuals illustrate the neurologic spectrum of LP, including variable mental retardation, personality changes, and mesial temporal calcificationand imply that significant neurologic involvement may be somewhat less common than previously thought. The cause of neurologic abnormalities was not clear from either neuroimaging or from what is known about ECM1 function. The severity of dermatologic abnormalities and hoarseness generally correlated with neurologic abnormalities, with Family 1 being somewhat more affected in all spheres than the other two families. Nevertheless, phenotype-genotype correlation was not obvious, possibly because of difficulty quantifying the neurologic phenotype and because of genetic complexity. PMID:21349189

2011-01-01

141

Genetic power of a Brazilian three-generation family with generalized aggressive periodontitis. II.  

PubMed

The genetic power of a Brazilian three-generation family with generalized aggressive periodontitis (GAgP) has been reported. The empirical logarithms of the odds (LOD) score thresholds for genetic linkage analysis of complex diseases proposed by Haines rely on confirmation from independent datasets. This study estimated the power of another large Brazilian family with GAgP for future linkage analysis. The three-generation family was seen at the Dental School of the Federal University of Bahia. Following the previously described methodology, full-mouth periodontal probing at 6 sites/tooth was performed in all 19 family members. Six out of 12 siblings were affected with GAgP. All affected family members were non-smokers and did not present diabetes or any other systemic condition or consanguinity. A parametric simulation (?=0) was performed on 100 replicates using the statistical software SLINK for linkage analysis. There was maximum expected LOD scores of 3.75 and 3.45 at penetrance rate F=0.98, and both studied phenocopy rates P=0.0 and P=0.02, respectively. The power of the study increased with the increase of the adopted penetrance rates in both studied phenocopy rates. The studied Brazilian three-generation family showed statistical power for future genetic linkage analysis of candidate genes to GAgP. PMID:21519652

Rapp, Gisela Estela; Pineda-Trujillo, Nicolas; McQuillin, Andrew; Tonetti, Maurizio

2011-01-01

142

Lipid transfer particle from the silkworm, Bombyx mori, is a novel member of the apoB/large lipid transfer protein family[S  

PubMed Central

Lipid transfer particle (LTP) is a high-molecular-weight, very high-density lipoprotein known to catalyze the transfer of lipids between a variety of lipoproteins, including both insects and vertebrates. Studying the biosynthesis and regulation pathways of LTP in detail has not been possible due to a lack of information regarding the apoproteins. Here, we sequenced the cDNA and deduced amino acid sequences for three apoproteins of LTP from the silkworm (Bombyx mori). The three subunit proteins of the LTP are coded by two genes, apoLTP-II/I and apoLTP-III. ApoLTP-I and apoLTP-II are predicted to be generated by posttranslational cleavage of the precursor protein, apoLTP-II/I. Clusters of amphipathic secondary structure within apoLTP-II/I are similar to Homo sapiens apolipoprotein B (apoB) and insect lipophorins. The apoLTP-II/I gene is a novel member of the apoB/large lipid transfer protein gene family. ApoLTP-III has a putative conserved juvenile hormone-binding protein superfamily domain. Expression of apoLTP-II/I and apoLTP-III genes was synchronized and both genes were primarily expressed in the fat body at the stage corresponding to increased lipid transport needs. We are now in a position to study in detail the physiological role of LTP and its biosynthesis and assembly. PMID:23812557

Yokoyama, Hiroshi; Yokoyama, Takeru; Yuasa, Masashi; Fujimoto, Hirofumi; Sakudoh, Takashi; Honda, Naoko; Fugo, Hajime; Tsuchida, Kozo

2013-01-01

143

A Large Family of Antivirulence Regulators Modulates the Effects of Transcriptional Activators in Gram-negative Pathogenic Bacteria  

PubMed Central

We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44–100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

Santiago, Araceli E.; Ruiz-Perez, Fernando; Jo, Noah Y.; Vijayakumar, Vidhya; Gong, Mei Q.; Nataro, James P.

2014-01-01

144

Schizophrenia and HLA: No association with PCR-SSOP typed classical loci in a large Irish familial sample.  

PubMed

Susceptibility to autoimmunity is strongly influence by genes clustered in the MHC region, particularly class I and class II antigens. It has been proposed that there is an immune component in the aetiology of schizophrenia, and the distribution of human leukocyte antigens (HLA) in schizophrenic patients and controls has been investigated in numerous studies. Positive associations have been reported between schizophrenia and the HLA-A1, A2, A9, B5, Cw4, and DR8 and negative associations with HLA-DR4 and HLA-DQbeta*0602. Small sample size, variable diagnostic methodology, unreliable laboratory and statistical procedures, and possible mismatching of cases and controls may have contributed to a lack of consistency of results to date. Therefore, in this investigation we used a large and carefully diagnosed homogeneous Irish familial schizophrenic sample compared with ethnically matched controls. All alleles were determined using polymerase chain reaction amplification followed by short specific oligoprobes. We found no evidence of association with 80 HLA alleles (some previously not examined) from 4 genes. Our data therefore do not support the involvement of these classical HLA loci in the aetiology of schizophrenia at least in these Irish families. The remaining classical HLA loci (HLA-B and HLA-C) should be typed when reliable DNA-based methods become available. PMID:10402512

Hawi, Z; Gibson, S; Straub, R E; Walsh, D; Kendler, K S; Gill, M

1999-08-20

145

A large family of antivirulence regulators modulates the effects of transcriptional activators in Gram-negative pathogenic bacteria.  

PubMed

We have reported that transcription of a hypothetical small open reading frame (orf60) in enteroaggregative E. coli (EAEC) strain 042 is impaired after mutation of aggR, which encodes a global virulence activator. We have also reported that the cryptic orf60 locus was linked to protection against EAEC diarrhea in two epidemiologic studies. Here, we report that the orf60 product acts as a negative regulator of aggR itself. The orf60 protein product lacks homology to known repressors, but displays 44-100% similarity to at least fifty previously undescribed small (<10 kDa) hypothetical proteins found in many gram negative pathogen genomes. Expression of orf60 homologs from enterotoxigenic E. coli (ETEC) repressed the expression of the AraC-transcriptional ETEC regulator CfaD/Rns and its regulon in ETEC strain H10407. Complementation in trans of EAEC 042orf60 by orf60 homologs from ETEC and the mouse pathogen Citrobacter rodentium resulted in dramatic suppression of aggR. A C. rodentium orf60 homolog mutant showed increased levels of activator RegA and increased colonization of the adult mouse. We propose the name Aar (AggR-activated regulator) for the clinically and epidemiologically important orf60 product in EAEC, and postulate the existence of a large family of homologs among pathogenic Enterobacteriaceae and Pasteurellaceae. We propose the name ANR (AraC Negative Regulators) for this family. PMID:24875828

Santiago, Araceli E; Ruiz-Perez, Fernando; Jo, Noah Y; Vijayakumar, Vidhya; Gong, Mei Q; Nataro, James P

2014-05-01

146

The Exceptionally Large Genome of Hendra Virus: Support for Creation of a New Genus within the Family Paramyxoviridae  

PubMed Central

An outbreak of acute respiratory disease in Hendra, a suburb of Brisbane, Australia, in September 1994 resulted in the deaths of 14 racing horses and a horse trainer. The causative agent was a new member of the family Paramyxoviridae. The virus was originally called Equine morbillivirus but was renamed Hendra virus (HeV) when molecular characterization highlighted differences between it and members of the genus Morbillivirus. Less than 5 years later, the closely related Nipah virus (NiV) emerged in Malaysia, spread rapidly through the pig population, and caused the deaths of over 100 people. We report the characterization of the HeV L gene and protein, the genome termini, and gene boundary sequences, thus completing the HeV genome sequence. In the highly conserved region of the L protein, the HeV sequence GDNE differs from the GDNQ found in almost all other nonsegmented negative-strand (NNS) RNA viruses. HeV has an absolutely conserved intergenic trinucleotide sequence, 3?-GAA-5?, and highly conserved transcription initiation and termination sequences similar to those of respiroviruses and morbilliviruses. The large genome size (18,234 nucleotides), the unique complementary genome terminal sequences of HeV, and the limited homology with other members of the Paramyxoviridae suggest that HeV, together with NiV, should be classified in a new genus in this family. The large genome of HeV also fills a gap in the spectrum of genome sizes observed with NNS RNA virus genomes. As such, it provides a further piece in the puzzle of NNS RNA virus evolution. PMID:11024125

Wang, Lin-Fa; Yu, Meng; Hansson, Eric; Pritchard, L. Ian; Shiell, Brian; Michalski, Wojtek P.; Eaton, Bryan T.

2000-01-01

147

The Prevalence and Impact of Large Sudden Improvements During Adolescent Therapy for Depression: A Comparison Across Cognitive-Behavioral, Family, and Supportive Therapy  

Microsoft Academic Search

This study assessed the treatment specificity and impact on outcome of large, abrupt symptomatic improvements occurring prior to and during cognitive-behavioral, family, and supportive therapy. Eighty-seven depressed adolescents receiving at least 8 therapy sessions were included. Abrupt large decreases in depressive symptoms were identified by changes in weekly Beck Depression Inventory scores. Overall, 28% experienced a pretreatment gain and 39%

Scott T. Gaynor; V. Robin Weersing; David J. Kolko; Boris Birmaher; Jungeun Heo; David A. Brent

2003-01-01

148

Diagnostic dilemma: a young woman with Fabry disease symptoms, no family history, and a "sequencing cryptic" ?-galactosidase a large deletion.  

PubMed

Fabry disease, an X-linked lysosomal storage disorder, results from the deficient activity of ?-galactosidase A (?-Gal A). In affected males, the clinical diagnosis is confirmed by the markedly decreased ?-Gal A activity. However, in female heterozygotes, the ?-Gal A activity can range from low to normal due to random X-chromosomal inactivation, and diagnostic confirmation requires identification of the family's ?-Gal A gene mutation. In a young female who had occasional acroparesthesias, corneal opacities, and 15 to 50% of the lower limit of normal leukocyte ?-Gal A activity, ?-Gal A sequencing in two expert laboratories did not identify a confirmatory mutation, presenting a diagnostic dilemma. A renal biopsy proved diagnostic and renewed efforts to detect an ?-Gal A mutation. Subsequent gene dosage analyses identified a large ?-Gal A deletion confirming her heterozygosity, and she was started on enzyme replacement therapy. Thus, gene dosage analyses can detect large deletions (>50bp) in suspect heterozygotes for X-linked and autosomal dominant diseases that are "sequencing cryptic," resolving molecular diagnostic dilemmas. PMID:21641253

Feldt-Rasmussen, Ulla; Dobrovolny, Robert; Nazarenko, Irina; Ballegaard, Martin; Hasholt, Lis; Rasmussen, Ase K; Christensen, Erik I; Sorensen, Soren S; Wibrand, Flemming; Desnick, Robert J

2011-11-01

149

Atrichia with papular lesions in two Pakistani consanguineous families resulting from mutations in the human hairless gene  

Microsoft Academic Search

Atrichia with papular lesions (APL) is a rare autosomal recessive form of total alopecia, characterized by hair loss soon\\u000a after birth and the development of papular lesions of keratin-filled cysts over extensive areas of the body. Mutations in\\u000a the hairless (hr) gene, a putative single zinc finger transcription factor, have been implicated in the pathogenesis of this\\u000a disorder. In the

Peter John; Muhammad Aslam; Muhammad Arshad Rafiq; Muhammad Amin-ud-din; Sayedul Haque; Wasim Ahmad

2005-01-01

150

Familial chondrocalcinosis in the Chiloe Islands, Chile.  

PubMed Central

Studies about chondrocalcinosis in the Chiloe Islands (Chile) showed the high frequency of the disease there and how most of it is aggregated in a few highly involved families. Pedigrees and the high degree of consanguinity among parents of index cases pointed to a recessive inheritance. The presence of common Caucasian anthropological features of genetic value in the patients and the lack of Indian mixture in three of the involved families, documented back to 1600, suggest a Caucasian origin of the mutation. Biochemical studies of the patients' synovial fluid showed a significant rise in pyrophosphate concentration. Calcium, phosphorus, and alkaline phosphatase concentrations were not different from a control group. PMID:168817

Reginato, A J; Hollander, J L; Martinez, V; Valenzuela, F; Schiapachasse, V; Covarrubias, E; Jacobelli, S; Arinoviche, R; Silcox, D; Ruiz, F

1975-01-01

151

Kabuki make-up syndrome: a syndrome of mental retardation, unusual facies, large and protruding ears, and postnatal growth deficiency.  

PubMed

A previously unrecognized mental retardation malformation syndrome was observed in five unrelated Japanese children. Consistent clinical features included moderate-to-severe mental retardation, progressive dwarfism of postnatal onset, a peculiar facies characterized by long palpebral fissures, with eversion of the lateral third of the lower eyelids, arched eyebrows, broad and depressed nasal tip, large prominent earlobes, short fifth fingers, abnormal dermatoglyphics including absence of digital triradius c or d, and frequent otitis media in infancy. Inconsistent abnormalities included epicanthal folds, cleft or high-arched palate, widely spaced teeth, low occipital hair line, scoliosis, and dislocation of the hip joint. Neither familial occurrence nor parental consanguinity was noted. The etiology of the malformation syndrome remains unknown. PMID:7277096

Niikawa, N; Matsuura, N; Fukushima, Y; Ohsawa, T; Kajii, T

1981-10-01

152

Application of a sensitive collection heuristic for very large protein families: Evolutionary relationship between adipose triglyceride lipase (ATGL) and classic mammalian lipases  

PubMed Central

Background Manually finding subtle yet statistically significant links to distantly related homologues becomes practically impossible for very populated protein families due to the sheer number of similarity searches to be invoked and analyzed. The unclear evolutionary relationship between classical mammalian lipases and the recently discovered human adipose triglyceride lipase (ATGL; a patatin family member) is an exemplary case for such a problem. Results We describe an unsupervised, sensitive sequence segment collection heuristic suitable for assembling very large protein families. It is based on fan-like expanding, iterative database searches. To prevent inclusion of unrelated hits, additional criteria are introduced: minimal alignment length and overlap with starting sequence segments, finding starting sequences in reciprocal searches, automated filtering for compositional bias and repetitive patterns. This heuristic was implemented as FAMILYSEARCHER in the ANNIE sequence analysis environment and applied to search for protein links between the classical lipase family and the patatin-like group. Conclusion The FAMILYSEARCHER is an efficient tool for tracing distant evolutionary relationships involving large protein families. Although classical lipases and ATGL have no obvious sequence similarity and differ with regard to fold and catalytic mechanism, homology links detected with FAMILYSEARCHER show that they are evolutionarily related. The conserved sequence parts can be narrowed down to an ancestral core module consisting of three ?-strands, one ?-helix and a turn containing the typical nucleophilic serine. Moreover, this ancestral module also appears in numerous enzymes with various substrate specificities, but that critically rely on nucleophilic attack mechanisms. PMID:16551354

Schneider, Georg; Neuberger, Georg; Wildpaner, Michael; Tian, Sun; Berezovsky, Igor; Eisenhaber, Frank

2006-01-01

153

Familial Isolated Hyperparathyroidism as a Variant of Multiple Endocrine Neoplasia Type 1 in a Large Danish Pedigree  

Microsoft Academic Search

We report here our genetic findings of a family in which 14 mem- bers were affected with isolated primary hyperparathyroidism. Hy- perparathyroidism is the main feature of multiple endocrine neopla- sia type 1 (MEN1), making the recently cloned MEN1 gene a prime candidate gene in this family. Significantly positive lod scores were achieved with D11S4946 (3.36) and D11S4940 (3.53), and

MUSTAPHA KASSEM; TORBEN A. KRUSE; FUNG KI WONG; CATHARINA LARSSON; BIN TEAN TEH

2010-01-01

154

Distinctive clinicopathological features of 2 large families with amyotrophic lateral sclerosis having L106V mutation in SOD1 gene.  

PubMed

A clinicopathological study of 2 families with familial amyotrophic lateral sclerosis was previously reported [1]. The present study continues to investigate these families, with detailed clinical, genetic, and neuropathological studies performed on 24 patients, including 5 autopsy cases of the families. A point mutation at codon 106 (L106V) in the copper/zinc superoxide dismutase-1 (SOD1) gene was identified in the families. Average age at onset was 52.0 ± 9.4 years, and initial symptoms were weakness and atrophy in the distal muscles of the lower extremities in most patients. Half of the patients showed neurogenic bladder (overactive bladder) and sensory impairment. The neurophysiological study showed peripheral/central conduction delay. Neuropathological examination revealed severe motor neuron loss with many bizarre reactive astrocytes in the spinal anterior horn. SOD1-immunopositive Lewy body-like hyaline inclusions and aggregation of neurofilaments were observed in the surviving anterior horn cells. Degeneration of the corticospinal tract was relatively minor. In addition, slight but diffuse gliosis was identified in the hypothalamus and medial nucleus of thalamus. Neurogenic bladder, sensory impairment, and degeneration of the hypothalamus and thalamus might be specific features in patients with familial amyotrophic lateral sclerosis with L106V mutation in the SOD1 gene. PMID:22647583

Hineno, Akiyo; Nakamura, Akinori; Shimojima, Yoshio; Yoshida, Kunihiro; Oyanagai, Kiyomitsu; Ikeda, Shu-ichi

2012-08-15

155

Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab community  

Microsoft Academic Search

We have observed an unusually high prevalence of dementia of the Alzheimer type (DAT) in Wadi Ara, an inbred Arab community in northern Israel comprising ? 850 persons over the age of 60 years. Family studies revealed that more than one-third of the DAT cases are members of one hamula (tribal group) within Wadi Ara. To map chromosomal loci contributing

Lindsay A. Farrer; Abdalla Bowirrat; Robert P. Friedland; Kristin Waraska; Amos D. Korczyn; Clinton T. Baldwin

2003-01-01

156

A large family with hereditary MTC: role of RET genetic analysis in differential diagnosis between MEN 2A and FMTC.  

PubMed

Germline mutations of the RET proto-oncogene cause three different cancer syndromes: multiple endocrine neoplasia type 2A (MEN 2A), multiple endocrine neoplasia type 2B (MEN 2B) and familial medullary thyroid carcinoma (FMTC). In the absence of biochemical and/or clinical evidence of pheochromocytoma and hyperparathyroidism, patients with MEN 2A disease display the same phenotype of FMTC disease, although prognosis and clinical management in both affected and unaffected familial members are quite different. We studied a family with hereditary MTC, whose proband was referred to us because of enlarged cervical nodes and increased calcitonin serum levels 28 years after the total thyroidectomy for MTC. Cervical node dissection was carried out and subsequently the presence of MTC metastasis was histologically confirmed. A RET genomic mutation at codon 634 (TGC-->TTC) was identified in the proband and in seven out of 19 familial members studied. Accordingly, a hereditary disease was suggested. However, the strong association of RET mutation at codon 634 with the presence of pheochromocytoma in MEN 2 disease suggested a more rigorous management in all gene carriers. Indeed, during the follow-up pheochromocytoma was subsequently identified in the proband. This finding suggests that all families with a pedigree suggestive of FMTC should be regarded at risk from MEN 2A disease, at least when a critical mutation in the RET cysteine domain is detected. PMID:11280716

Chiefari, E; Chiarella, R; Crocetti, U; Tardio, B; Arturi, F; Russo, D; Trischitta, V; Filetti, S; Zingrillo, M

2001-01-01

157

Familial mitochondrial DNA depletion in liver: haplotype analysis of candidate genes  

Microsoft Academic Search

Two sons and one daughter of healthy consanguineous parents presented with fatal hepatic failure in association with severe\\u000a depletion of mitochondrial (mt)DNA in liver; a third son is healthy. Other published cases of mtDNA depletion concern single\\u000a members of a family, which excludes the use of haplotype analysis. In the family presented here, the inheritance of the genes\\u000a for mitochondrial

Johannes N. Spelbrink; Mieke J. M. Van Galen; R. Zwart; Henk D. Bakker; Anja Rovio; Howard T. Jacobs; Coby Van den Bogert

1998-01-01

158

A novel mutation in GJA3 associated with congenital Coppock-like cataract in a large Chinese family  

PubMed Central

Purpose To identify the potential pathogenic mutation over five generations of a Chinese family with congenital Coppock-like cataracts (CCL). Methods We investigated five generations of a Chinese family affected with CCL. The family resides in a relatively isolated region of northern China. Peripheral blood samples were collected from all of the family members, and genomic DNA was then extracted from the blood samples. A genome-wide linkage scan was performed using about 400 microsatellite markers. Two-point LOD (linkage odd disequilibrium) scores (Z) were calculated using the LINKAGE programs (ver. 5.1). Cyrillic software processed the resulting haplotypes. Mutation detection was performed in the candidate gene by direct sequencing. Results The maximum LOD score was obtained at marker D13S175 (lod score [Zmax]=5.90; recombination fraction [?]=0.0). Haplotype analysis traced the disease gene to a 6.99-cM interval bounded by D13S1316 and D13S1275 on chromosome 13q12.11. Direct sequencing of the candidate gene GJA3 (gap junction protein alpha-3) revealed a c.427G>A transition in exon 2 of GJA3 that co-segregated with the cataract in the family members and was not observed in 100 control patients. This single-nucleotide change resulted in the substitution of a highly conserved glycine by arginine (G143R). Conclusions The present study identified a novel mutation in GJA3 that causes CCL. As the first report to relate p.G143R mutation in GJA3, it expands the mutation spectrum of GJA3. Our report is the first in identification of the mutation of GJA3 in the cytoplasmic-loop domain. This mutation is associated with multiple members of a five-generation family with congenital CCL. PMID:22876138

Qu, Xin; Su, Sheng; Guan, Linan; Liu, Ping

2012-01-01

159

The major 85-kD surface antigen of the mammalian form of Trypanosoma cruzi is encoded by a large heterogeneous family of simultaneously expressed genes  

PubMed Central

Trypanosoma cruzi is an obligate intracellular protozoan parasite. The parasite mammalian stage surface antigens exhibit extensive antigenic diversity. We have characterized a family of T. cruzi genes that code for a polymorphic set of 85-kD surface antigens, the SA85-1 antigens. The family contains greater than 100 genes and pseudogenes, of which a minimum of nine are transcribed. The gene family is expressed in the mammalian stage only. A subset of the gene family is present in two telomere-linked copies in the genome. Telomere linkage of other expressed SA85-1 genes has not been demonstrated. We have shown that at least three members of the SA85-1 gene family encode antigens at the surface of the mammalian stage of the parasite. Interestingly, these three antigens are expressed on all the trypanosomes examined. This suggests that T. cruzi simultaneously expresses a large repertoire of similar, but diverse antigens at its surface. Thus, T. cruzi exhibits extensive antigenic diversity in a system unique from that of African trypanosomes, perhaps reflecting its intracellular niche. PMID:1695668

1990-01-01

160

Clinical variability of the cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy phenotype in two siblings of a large family showing the same mutation  

PubMed Central

A 44-year-old Albanian male was consulted and diagnosed with dementia. His magnetic resonance imaging suggested diffuse white matter changes. The suspicion of cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) was raised, and a genetic analysis confirmed such a suspicion through uncovering a pathogenic mutation at the level of exon 4 (c.475C>T) of chromosome 19. The patient came from a large family of 13 children, all of whom underwent clinical, genetic, and imaging examination. The pathogenic mutation was found present only in his eldest sister (50 years old), and she presented also very suggestive signs of CADASIL in her respective imaging study, but without any clinically significant counterpart. All other siblings were free from clinical and radiological signs of the disorder. Our opinion was that we were dealing with a mutation showing a very low level of penetrance, with only two siblings affected in a large Albanian family with 13 children. PMID:24124395

Vyshka, Gentian; Kruja, Jera

2013-01-01

161

To integrate family planning into the building up of mental civilization by offering comprehensive services.  

PubMed

The government of Nangong City, a newly instituted city with a relatively large proportion of agricultural workers has integrated family planning into the building up of mental civilization. As a result, in 1986, the family planning practice rate was 98.4%. One way the government accomplished this was by developing production to eliminate poverty, to show that population development has a significant impact on socioeconomic development. To help change people's attitudes about family planning, the government 1) used publicity, such as speechmaking, mass media, and courses in population theory; 2) awarded those who made contributions; 3) carried out publicity and education in accordance with characteristics of different groups of people; and 4) encouraged bridegrooms to live with their wives' families if the wives' parents had had no son. Another technique the government used as the popularization of scientific knowledge about population theory, physiology and hygiene, birth control, and eugenics and health in births. A 4th method was to popularize knowledge of laws and regulations, such as of early marriage and consanguineous marriage. 5th, the government developed social security undertakings: 1) giving priority to single-child families and 2) taking care of the elderly. Finally, the government improved maternal and child care by 1) providing premarital health care; 2) creating a project for healthier births and better upbringing; 3) family planning workers showing warm concern for reproductive women; and 4) controlling women's diseases and providing health care knowledge, as well as family planning services. These 6 activities have resulted in 1) the decreasing momentum of per capita arable land being controlled, 2) 1-child couples having more time to learn, 3) the development of educational undertakings, 4) a change in people's traditional practices, and 5) improvement in the understanding of patriotism. PMID:12281754

1988-03-01

162

A Large Deletion Disrupts the Exon 3 Transcription Activation Domain of the BRCA2 Gene in a Breast\\/Ovarian Cancer Family1  

Microsoft Academic Search

We describe the identification of a large deletion in the BRCA2 gene as the disease-causing mutation in a Swedish breast\\/ovarian cancer family. The 5068-bp deletion encompassed the 3' region of exon 3, including the 3' splice site and most of intron 3, and it resulted on the niRNA level in an inframe exon 3 skipping. The junction site also included

Margarete Nordling; Yvonne Engwall; Arne Wallgren; Tommy Martinsson

1998-01-01

163

The large soybean (Glycine max) WRKY TF family expanded by segmental duplication events and subsequent divergent selection among subgroups  

PubMed Central

Background WRKY genes encode one of the most abundant groups of transcription factors in higher plants, and its members regulate important biological process such as growth, development, and responses to biotic and abiotic stresses. Although the soybean genome sequence has been published, functional studies on soybean genes still lag behind those of other species. Results We identified a total of 133 WRKY members in the soybean genome. According to structural features of their encoded proteins and to the phylogenetic tree, the soybean WRKY family could be classified into three groups (groups I, II, and III). A majority of WRKY genes (76.7%; 102 of 133) were segmentally duplicated and 13.5% (18 of 133) of the genes were tandemly duplicated. This pattern was not apparent in Arabidopsis or rice. The transcriptome atlas revealed notable differential expression in either transcript abundance or in expression patterns under normal growth conditions, which indicated wide functional divergence in this family. Furthermore, some critical amino acids were detected using DIVERGE v2.0 in specific comparisons, suggesting that these sites have contributed to functional divergence among groups or subgroups. In addition, site model and branch-site model analyses of positive Darwinian selection (PDS) showed that different selection regimes could have affected the evolution of these groups. Sites with high probabilities of having been under PDS were found in groups I, II c, II e, and III. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. Conclusions In this work, all the WRKY genes, which were generated mainly through segmental duplication, were identified in the soybean genome. Moreover, differential expression and functional divergence of the duplicated WRKY genes were two major features of this family throughout their evolutionary history. Positive selection analysis revealed that the different groups have different evolutionary rates. Together, these results contribute to a detailed understanding of the molecular evolution of the WRKY gene family in soybean. PMID:24088323

2013-01-01

164

Deletion of exons 1-3 of the MEN1 gene in a large Italian family causes the loss of menin expression.  

PubMed

Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disease, characterized by parathyroid adenomas, endocrine gastroenteropancreatic tumors and pituitary adenomas, due to inactivating mutations of the MEN1 gene (chromosome 11q13). MEN1 mutations are mainly represented by nonsense, deletions/insertions, splice site or missense mutations that can be detected by direct sequencing of genomic DNA. However, MEN1 patients with large heterozygous deletions may escape classical genetic screening and may be misidentified as phenocopies, thereby hindering proper clinical surveillance. We employed a real-time polymerase chain reaction application, the TaqMan copy number variation assay, to evaluate a family in which we failed to identify an MEN1 mutation by direct sequencing, despite a clear clinical diagnosis of MEN1 syndrome. Using the TaqMan copy number variation assay we identified a large deletion of the MEN1 gene involving exons 1 and 2, in three affected family members, but not in the other nine family members that were to date clinically unaffected. The same genetic alteration was not found in a group of ten unaffected subjects, without family history of endocrine tumors. The MEN1 deletion was further confirmed by multiplex ligation-dependent probe amplification, which showed the deletion extended from exon 1 to exon 3. This new approach allowed us to correctly genetically diagnose three clinical MEN1 patients that were previously considered as MEN1 phenocopies. More importantly, we excluded the presence of genetic alterations in the unaffected family members. These results underline the importance of using a variety of available biotechnology approaches when pursuing a genetic diagnosis in a clinically suggestive setting of inherited endocrine cancer. PMID:24522746

Zatelli, Maria Chiara; Tagliati, Federico; Di Ruvo, Mauro; Castermans, Emilie; Cavazzini, Luigi; Daly, Adrian F; Ambrosio, Maria Rosaria; Beckers, Albert; degli Uberti, Ettore

2014-06-01

165

Congenital hypothyroidism: increased incidence in Asian families.  

PubMed Central

Screening in the North West health region of England showed a significantly higher incidence of congenital hypothyroidism in Asian families--1/918 compared with 1/3391 in non-Asians. This could only in part be explained by consanguinity. No differences were found in birth order, season of birth, gestational age, or birth weight between normal infants and those with congenital hypothyroidism. There was a significantly higher incidence of additional congenital abnormalities (9%) and a significantly increased mortality (5%) in infants with congenital hypothyroidism compared with unaffected infants. PMID:3415295

Rosenthal, M; Addison, G M; Price, D A

1988-01-01

166

ISH51: a large, degenerate family of insertion sequence-like elements in the genome of the archaebacterium, Halobacterium volcanii.  

PubMed Central

We describe a new family of repetitive elements in the genome of the archaebacterium Halobacterium volcanii. There are some 20-30 copies of this element, which we designate ISH51. Sequenced copies show typical insertion sequence characteristics (terminal inverted repeats, direct flanking repeats of "target site" DNA). However, members of the ISH51 family are highly heterogeneous, showing on average only 85% primary sequence homology; and some genomic copies appear to be severely truncated. Some ISH51 elements are clustered together in regions of relatively AT-rich DNA. There are at least five such AT-rich "islands" in the H. volcanii genome. Repetitive sequences homologous to ISH51 are found in the genomes of most Halobacterium and Halococcus species. Images PMID:3020501

Hofman, J D; Schalkwyk, L C; Doolittle, W F

1986-01-01

167

Plexins Are a Large Family of Receptors for Transmembrane, Secreted, and GPI-Anchored Semaphorins in Vertebrates  

Microsoft Academic Search

In Drosophila, plexin A is a functional receptor for semaphorin-1a. Here we show that the human plexin gene family comprises at least nine members in four subfamilies. Plexin-B1 is a receptor for the transmembrane semaphorin Sema4D (CD100), and plexin-C1 is a receptor for the GPI-anchored semaphorin Sema7A (Sema-K1). Secreted (class 3) semaphorins do not bind directly to plexins, but rather

Luca Tamagnone; Stefania Artigiani; Hang Chen; Zhigang He; Guo-li Ming; Hong-jun Song; Alain Chedotal; Margaret L. Winberg; Corey S. Goodman; Mu-ming Poo; Marc Tessier-Lavigne; Paolo M. Comoglio

1999-01-01

168

Age-related Macular Degeneration Clinical Features in a Large Family and Linkage to Chromosome 1q  

Microsoft Academic Search

Methods: An ARMD pedigree was identified, and the disease state of family members was documented by stereoscopic fundus photography and was classified us- ing a modified version of the Wisconsin Age-Related Maculopathy Grading System. A genome-wide screen at approximately 6-centimorgan spacing using a DNA- pooling strategy combined with shared-segment analy- sis was used to identify likely chromosomal regions. The entire

Michael L. Klein; Dennis W. Schultz; Al Edwards; Tara C. Matise; Kristal Rust; C. Blair Berselli; Karmen Trzupek; Richard G. Weleber; Jurg Ott; Mary K. Wirtz; Ted S. Acott; Arch Ophthalmol

1998-01-01

169

A Family-Wide RT-PCR Assay for Detection of Paramyxoviruses and Application to a Large-Scale Surveillance Study  

PubMed Central

Family-wide molecular diagnostic assays are valuable tools for initial identification of viruses during outbreaks and to limit costs of surveillance studies. Recent discoveries of paramyxoviruses have called for such assay that is able to detect all known and unknown paramyxoviruses in one round of PCR amplification. We have developed a RT-PCR assay consisting of a single degenerate primer set, able to detect all members of the Paramyxoviridae family including all virus genera within the subfamilies Paramyxovirinae and Pneumovirinae. Primers anneal to domain III of the polymerase gene, with the 3? end of the reverse primer annealing to the conserved motif GDNQ, which is proposed to be the active site for nucleotide polymerization. The assay was fully optimized and was shown to indeed detect all available paramyxoviruses tested. Clinical specimens from hospitalized patients that tested positive for known paramyxoviruses in conventional assays were also detected with the novel family-wide test. A high-throughput fluorescence-based RT-PCR version of the assay was developed for screening large numbers of specimens. A large number of samples collected from wild birds was tested, resulting in the detection of avian paramyxoviruses type 1 in both barnacle and white-fronted geese, and type 8 in barnacle geese. Avian metapneumovirus type C was found for the first time in Europe in mallards, greylag geese and common gulls. The single round family-wide RT-PCR assay described here is a useful tool for the detection of known and unknown paramyxoviruses, and screening of large sample collections from humans and animals. PMID:22496880

van Boheemen, Sander; Bestebroer, Theo M.; Verhagen, Josanne H.; Osterhaus, Albert D. M. E.; Pas, Suzan D.; Herfst, Sander; Fouchier, Ron A. M.

2012-01-01

170

Identification of rare DNA sequence variants in high-risk autism families and their prevalence in a large case/control population  

PubMed Central

Background Genetics clearly plays a major role in the etiology of autism spectrum disorders (ASDs), but studies to date are only beginning to characterize the causal genetic variants responsible. Until recently, studies using multiple extended multi-generation families to identify ASD risk genes had not been undertaken. Methods We identified haplotypes shared among individuals with ASDs in large multiplex families, followed by targeted DNA capture and sequencing to identify potential causal variants. We also assayed the prevalence of the identified variants in a large ASD case/control population. Results We identified 584 non-conservative missense, nonsense, frameshift and splice site variants that might predispose to autism in our high-risk families. Eleven of these variants were observed to have odds ratios greater than 1.5 in a set of 1,541 unrelated children with autism and 5,785 controls. Three variants, in the RAB11FIP5, ABP1, and JMJD7-PLA2G4B genes, each were observed in a single case and not in any controls. These variants also were not seen in public sequence databases, suggesting that they may be rare causal ASD variants. Twenty-eight additional rare variants were observed only in high-risk ASD families. Collectively, these 39 variants identify 36 genes as ASD risk genes. Segregation of sequence variants and of copy number variants previously detected in these families reveals a complex pattern, with only a RAB11FIP5 variant segregating to all affected individuals in one two-generation pedigree. Some affected individuals were found to have multiple potential risk alleles, including sequence variants and copy number variants (CNVs), suggesting that the high incidence of autism in these families could be best explained by variants at multiple loci. Conclusions Our study is the first to use haplotype sharing to identify familial ASD risk loci. In total, we identified 39 variants in 36 genes that may confer a genetic risk of developing autism. The observation of 11 of these variants in unrelated ASD cases further supports their role as ASD risk variants. PMID:24467814

2014-01-01

171

Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A.  

PubMed

Mutations in the KCNQ2 and KCNQ3 genes encoding for Kv 7.2 (KCNQ2; Q2) and Kv 7.3 (KCNQ3; Q3) voltage-dependent K(+) channel subunits, respectively, cause neonatal epilepsies with wide phenotypic heterogeneity. In addition to benign familial neonatal epilepsy (BFNE), KCNQ2 mutations have been recently found in families with one or more family members with a severe outcome, including drug-resistant seizures with psychomotor retardation, electroencephalogram (EEG) suppression-burst pattern (Ohtahara syndrome), and distinct neuroradiological features, a condition that was named "KCNQ2 encephalopathy." In the present article, we describe clinical, genetic, and functional data from 17 patients/families whose electroclinical presentation was consistent with the diagnosis of BFNE. Sixteen different heterozygous mutations were found in KCNQ2, including 10 substitutions, three insertions/deletions and three large deletions. One substitution was found in KCNQ3. Most of these mutations were novel, except for four KCNQ2 substitutions that were shown to be recurrent. Electrophysiological studies in mammalian cells revealed that homomeric or heteromeric KCNQ2 and/or KCNQ3 channels carrying mutant subunits with newly found substitutions displayed reduced current densities. In addition, we describe, for the first time, that some mutations impair channel regulation by syntaxin-1A, highlighting a novel pathogenetic mechanism for KCNQ2-related epilepsies. PMID:24375629

Soldovieri, Maria Virginia; Boutry-Kryza, Nadia; Milh, Mathieu; Doummar, Diane; Heron, Benedicte; Bourel, Emilie; Ambrosino, Paolo; Miceli, Francesco; De Maria, Michela; Dorison, Nathalie; Auvin, Stephane; Echenne, Bernard; Oertel, Julie; Riquet, Audrey; Lambert, Laetitia; Gerard, Marion; Roubergue, Anne; Calender, Alain; Mignot, Cyril; Taglialatela, Maurizio; Lesca, Gaetan

2014-03-01

172

Novel deletion in the pre-mRNA splicing gene PRPF31 causes autosomal dominant retinitis pigmentosa in a large Chinese family.  

PubMed

We report the identification of a novel 12 bp deletion of the pre-mRNA splicing gene PRPF31 in a large Chinese family with autosomal dominant retinitis pigmentosa (adRP). This mutation results in the deletion of four amino acids (DeltaH(111)K(112)F(113)I(114)) including H(111), an amino acid residue that is highly conserved throughout evolution. The 12 bp deletion co-segregates with the disease phenotype in 19 RP patients in the family, but is not present in unaffected relatives or 100 normal individuals. Our data indicate that the novel 12 bp deletion in PRPF31 causes retinitis pigementosa in this Chinese adRP family. In contrast to the incomplete penetrance observed in most adRP families linked to chromosome band 19q13.4 (RP11), the 12 bp PRPF31 deletion identified in this study appears to show high penetrance. These data expand the spectrum of PRPF31 mutations causing adRP, and confirm the role of PRPF31 in the pathogenesis of RP. PMID:12923864

Wang, Lejin; Ribaudo, Michael; Zhao, Kanxing; Yu, Ning; Chen, Qiuyun; Sun, Qiuxiang; Wang, Liming; Wang, Qing

2003-09-01

173

Congenital muscular dystrophy associated with calf hypertrophy, microcephaly and severe mental retardation in three Italian families: evidence for a novel CMD syndrome  

Microsoft Academic Search

We describe four Italian patients (aged 3, 4, 12, and 13 years ) affected by a novel autosomal form of recessive congenital muscular dystrophy. These patients were from three non-consanguineous families and presented an almost identical phenotype. This was characterized by hypotonia at birth, joint contractures associated with severe psychomotor retardation, absent speech, inability to walk and almost no interest

Marcello Villanova; Eugenio Mercuri; Enrico Bertini; Patrizia Sabatelli; Lucia Morandi; Marina Mora; Caroline Sewry; Martin Brockington; Susan C Brown; Ana Ferreiro; Nadir M Maraldi; Tatsushi Toda; Pascale Guicheney; Luciano Merlini; Francesco Muntoni

2000-01-01

174

A novel variation in the AVP gene resulting in familial neurohypophyseal diabetes insipidus in a large Italian kindred.  

PubMed

Familial neurohypophyseal diabetes insipidus (FNDI) is mostly an autosomal dominant inherited disorder presenting with severe polydipsia and polyuria typically in early childhood. To date, 69 different variations in the AVP gene encoding the AVP prohormone have been identified in autosomal dominant FNDI (adFNDI). In this study we present a family of seven generations, in which a novel variation in the AVP gene seems to cause adFNDI. Clinical assessment by 24 h urine collection, water deprivation test, desmopressin (dDAVP) challenge, and magnetic resonance imaging (MRI) of the posterior pituitary are presented. The diagnosis of adFNDI was confirmed by direct DNA sequence analysis of the AVP gene. Inheritance pattern and clinical history clearly pointed towards adFNDI. Inability of concentrating urine upon dehydration was demonstrated by a water deprivation test, and neurohypophyseal diabetes insipidus was strongly suspected after dDAVP administration, during which renal concentration ability quadrupled. MRI revealed a very weak pituitary "bright spot" in each of six subjects and a further reduction in the size of the neurohypophysis in a 7-year follow-up MRI scan in one subject. DNA sequence analysis revealed heterozygousity for a novel g.1785T > C gene variation predicting a p.Leu63Pro substitution in four affected subjects. Genetic testing in the diagnostic evaluation of families in which diabetes insipidus segregates is highly recommended in that interpretation of clinical assessments can be difficult. Furthermore, presymptomatic diagnosis can ease the parental concern of the carrier status of their offspring, and also avoid unnecessary surveillance of those being unaffected. PMID:22695750

Birkegaard, Camilla; Christensen, Jane H; Falorni, Alberto; Marzotti, Stefania; Minarelli, Viviana; Gregersen, Niels; Rittig, Søren

2013-06-01

175

First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer  

PubMed Central

Background CHEK2 is a multi-cancer susceptibility gene whose common germline mutations are known to contribute to the risk of developing breast and prostate cancer. Case presentation Here, we describe an Italian family with a high number of cases of breast cancer and other types of tumour subjected to the MLPA test to verify the presence of BRCA1, BRCA2 and CHEK2 deletions and duplications. We identified a new 23-kb duplication in the CHEK2 gene extending from intron 5 to 13 that was associated with breast cancer in the family. The presence and localisation of the alteration was confirmed by a second analysis by Next-Generation Sequencing. Conclusions This finding suggests that CHEK2 mutations are heterogeneous and that techniques other than sequencing, such as MLPA, are needed to identify CHEK2 mutations. It also indicates that CHEK2 rare variants, such as duplications, can confer a high susceptibility to cancer development and should thus be studied in depth as most of our knowledge of CHEK2 concerns common mutations. PMID:24986639

2014-01-01

176

Topological properties of large-scale structural brain networks in children with familial risk for reading difficulties  

PubMed Central

Developmental dyslexia is a neurobiological deficit characterized by persistent difficulty in learning to read in children and adults who otherwise possess normal intelligence. Functional and structural connectivity data suggest that developmental dyslexia could be a disconnection syndrome. However, whether abnormalities in connectivity exist in beginning readers at-risk for reading difficulties is unknown. Using graphtheoretical analysis, we investigated differences in global and regional topological properties of structural brain networks in 42 beginning readers with (FH+) and without (FH?) familial risk for reading difficulties. We constructed separate structural correlation networks based on measures of surface area and cortical thickness. Results revealed changes in topological properties in brain regions known to be abnormal in dyslexia (left supramarginal gyrus, left inferior frontal gyrus) in the FH+ group mainly in the network constructed from measures of cortical surface area. We also found alterations in topological properties in regions that are not often advertised as dyslexia but nonetheless play important role in reading (left posterior cingulate, hippocampus, and left precentral gyrus). To our knowledge, this is the first report of altered topological properties of structural correlation networks in children at risk for reading difficulty, and motivates future studies that examine the mechanisms underlying how these brain networks may mediate the influences of family history on reading outcome. PMID:23333415

Hosseini, S.M. Hadi; Black, Jessica M.; Soriano, Teresa; Bugescu, Nicolle; Martinez, Rociel; Raman, Mira M.; Kesler, Shelli R.; Hoeft, Fumiko

2013-01-01

177

A clinical evaluation tool for SNP arrays, especially for autosomal recessive conditions in offspring of consanguineous parents  

PubMed Central

Purpose: This report describes a fast online tool to accelerate and improve clinical interpretation of single nucleotide polymorphism array results for diagnostic purposes, when consanguinity or inbreeding is identified. Methods: We developed a web-based program that permits entry of regions of homozygosity and, using OMIM, UCSC, and NCBI databases, retrieves genes within these regions as well as their associated autosomal recessive disorders. Relevant OMIM Clinical Synopses can be searched, using key clinical terms permitting further filtering for candidate genes and disorders. Results: The tool aids the clinician by arriving at a short list of relevant candidate disorders, guiding the continued diagnostic work-up. Its efficacy is illustrated by presenting seven patients who were diagnosed using this tool. Conclusion: The online single nucleotide polymorphism array evaluation tool rapidly and systematically identifies relevant genes and associated conditions mapping to identified regions of homozygosity. The built-in OMIM clinical feature search allows the user to further filter to reach a short list of candidate conditions relevant for the diagnosis, making it possible to strategize more focused diagnostic testing. The tabulated results can be downloaded and saved to the desktop in an Excel format. Its efficacy is illustrated by providing a few clinical examples. PMID:23100014

Wierenga, Klaas J.; Jiang, Zhijie; Yang, Amy C.; Mulvihill, John J.; Tsinoremas, Nicholas F.

2013-01-01

178

Immunoglobulin heavy chain variable region and major histocompatibility region genes are linked to induced graves' disease in females from two very large families of recombinant inbred mice.  

PubMed

Graves' hyperthyroidism is caused by antibodies to the TSH receptor (TSHR) that mimic thyroid stimulation by TSH. Stimulating TSHR antibodies and hyperthyroidism can be induced by immunizing mice with adenovirus expressing the human TSHR A-subunit. Prior analysis of induced Graves' disease in small families of recombinant inbred (RI) female mice demonstrated strong genetic control but did not resolve trait loci for TSHR antibodies or elevated serum T4. We investigated the genetic basis for induced Graves' disease in female mice of two large RI families and combined data with earlier findings to provide phenotypes for 178 genotypes. TSHR antibodies measured by inhibition of TSH binding to its receptor were highly significantly linked in the BXD set to the major histocompatibility region (chromosome 17), consistent with observations in 3 other RI families. In the LXS family, we detected linkage between T4 levels after TSHR-adenovirus immunization and the Ig heavy chain variable region (Igvh, chromosome 12). This observation is a key finding because components of the antigen binding region of Igs determine antibody specificity and have been previously linked to induced thyroid-stimulating antibodies. Data from the LXS family provide the first evidence in mice of a direct link between induced hyperthyroidism and Igvh genes. A role for major histocompatibility genes has now been established for genetic susceptibility to Graves' disease in both humans and mice. Future studies using arrays incorporating variation in the complex human Ig gene locus will be necessary to determine whether Igvh genes are also linked to Graves' disease in humans. PMID:25051451

McLachlan, Sandra M; Aliesky, Holly; Banuelos, Bianca; Magana, Jessica; Williams, Robert W; Rapoport, Basil

2014-10-01

179

Transient receptor potential: a large family of new channels of which several are involved in cardiac arrhythmia.  

PubMed

The transient receptor potential (TRP) family of ion channels comprises more than 50 cation-permeable channels expressed throughout the animal kingdom. TRPs can be grouped into 7 main subfamilies according to structural homology: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), TRPA (ankyrin), and TRPN (NO mechanopotential). During the past 20 years, the cloning and characterization after reexpression of most members of these cation channels have led to a plethora of data and more recently to some understanding of their roles in various cells and tissues. Specifically in the heart, TRPs are known to be involved in various diseases, including hypertrophy, heart failure, and arrhythmia. The later part of this review focuses on the potential contribution of TRPs to cardiac rhythm and their potential proarrhythmic effects. Furthermore, several neurotransmitters that activate the formation of diacylglycerol could modulate cardiac rhythm or, like ATP, induce arrhythmia. PMID:19234573

Vassort, Guy; Alvarez, Julio

2009-02-01

180

A large deletion disrupts the exon 3 transcription activation domain of the BRCA2 gene in a breast/ovarian cancer family.  

PubMed

We describe the identification of a large deletion in the BRCA2 gene as the disease-causing mutation in a Swedish breast/ovarian cancer family. The 5068-bp deletion encompassed the 3' region of exon 3, including the 3' splice site and most of intron 3, and it resulted on the mRNA level in an inframe exon 3 skipping. The junction site also included an insertion of 4 bp (CCAT). The mutation (nt504del5068insCCAT) resulted in a genotype absent of the two transcription activation regions localized to exon 3. The breast cancer phenotype associated with the described mutation resembled the phenotype of breast cancer found in both BRCA1 and BRCA2 mutation carriers. This is the first report of a large deletion as the disease-causing mutation in the BRCA2 gene. PMID:9537232

Nordling, M; Karlsson, P; Wahlström, J; Engwall, Y; Wallgren, A; Martinsson, T

1998-04-01

181

Insulin-resistance and metabolic syndrome are related to executive function in women in a large family-based study  

PubMed Central

While type 2 diabetes is well-known to be associated with poorer cognitive performance, few studies have reported on the association of metabolic syndrome (MetS) and contributing factors, such as insulin-resistance (HOMA-IR), low adiponectin-, and high C-reactive protein (CRP)- levels. We studied whether these factors are related to cognitive function and which of the MetS components are independently associated. The study was embedded in an ongoing family-based cohort study in a Dutch population. All participants underwent physical examinations, biomedical measurements, and neuropsychological testing. Linear regression models were used to determine the association between MetS, HOMA-IR, adiponectin levels, CRP, and cognitive test scores. Cross-sectional analyses were performed in 1,898 subjects (mean age 48 years, 43% men). People with MetS had significantly higher HOMA-IR scores, lower adiponectin levels, and higher CRP levels. MetS and high HOMA-IR were associated with poorer executive function in women (P = 0.03 and P = 0.009). MetS and HOMA-IR are associated with poorer executive function in women. PMID:20585974

Schuur, M.; Henneman, P.; van Swieten, J. C.; Zillikens, M. C.; de Koning, I.; Janssens, A. C. J. W.; Witteman, J. C. M.; Aulchenko, Y. S.; Frants, R. R.; Oostra, B. A.; van Dijk, K. Willems

2010-01-01

182

GPR50 is not associated with childhood-onset mood disorders in a large sample of Hungarian families.  

PubMed

We investigated the relationship of the gene for the X-linked orphan G protein-coupled receptor (GPR50) to childhood-onset mood disorders in a sample of 384 families with 468 affected children and adolescents collected in Hungary. Our choice of this gene for study was based on a previous report of an association of GPR50 with bipolar disorder and major depressive disorder. A significant association with the deletion allele of an insertion/deletion polymorphism (Delta502-505) located in exon 2 had been reported in a sample of 226 patients with major depressive disorder and 264 patients with bipolar disorder. The association was more significant in females compared with males in those samples. We used for this study a polymorphism in complete linkage disequilibrium with the Delta502-505 polymorphism, Thr532Ala (rs561077), and two additional polymorphisms, Val606Ile (rs13440581) and an intronic polymorphism (rs2072621). We found no evidence for an association for the markers analyzed individually, nor for haplotypes of these markers. Further, we found no evidence of association when the results were analyzed in girls only (n=215). We, therefore, failed to replicate the previous association of this gene with mood disorders. PMID:18075476

Feng, Yu; Wigg, Karen; King, Nicole; Vetró, Agnes; Kiss, Eniko; Kapornai, Krisztina; Mayer, László; Gádoros, Júlia; Kennedy, James L; Kovacs, Maria; Barr, Cathy L

2007-12-01

183

Extending the spectrum of Ellis van Creveld syndrome: a large family with a mild mutation in the EVC gene  

PubMed Central

Background Ellis-van Creveld (EvC) syndrome is characterized by short limbs, short ribs, postaxial polydactyly, dysplastic nails and teeth and is inherited in an autosomal recessive pattern. We report a family with complex septal cardiac defects, rhizomelic limb shortening, and polydactyly, without the typical lip, dental, and nail abnormalities of EvC. The phenotype was inherited in an autosomal recessive pattern, with one instance of pseudodominant inheritance. Methods Because of the phenotypic overlap with EvC, microsatellite markers were used to test for linkage to the EVC/EVC2 locus. The results did not exclude linkage, so samples were sequenced for mutations. Results We identified a c.1868T>C mutation in EVC, which predicts p.L623P, and was homozygous in affected individuals. Conclusion We conclude that this EVC mutation is hypomorphic and that such mutations can cause a phenotype of cardiac and limb defects that is less severe than typical EvC. EVC mutation analysis should be considered in patients with cardiac and limb malformations, even if they do not manifest typical EvC syndrome. PMID:18947413

Ulucan, Hakan; Gul, Davut; Sapp, Julie C; Cockerham, John; Johnston, Jennifer J; Biesecker, Leslie G

2008-01-01

184

The large-conductance calcium-activated potassium channel holds the key to the conundrum of familial hypokalemic periodic paralysis  

PubMed Central

Purpose Familial hypokalemic periodic paralysis (HOKPP) is an autosomal dominant channelopathy characterized by episodic attacks of muscle weakness and hypokalemia. Mutations in the calcium channel gene, CACNA1S, or the sodium channel gene, SCN4A, have been found to be responsible for HOKPP; however, the mechanism that causes hypokalemia remains to be determined. The aim of this study was to improve the understanding of this mechanism by investigating the expression of calcium-activated potassium (KCa) channel genes in HOKPP patients. Methods We measured the intracellular calcium concentration with fura-2-acetoxymethyl ester in skeletal muscle cells of HOKPP patients and healthy individuals. We examined the mRNA and protein expression of KCa channel genes (KCNMA1, KCNN1, KCNN2, KCNN3, and KCNN4) in both cell types. Results Patient cells exhibited higher cytosolic calcium levels than normal cells. Quantitative reverse transcription polymerase chain reaction analysis showed that the mRNA levels of the KCa channel genes did not significantly differ between patient and normal cells. However, western blot analysis showed that protein levels of the KCNMA1 gene, which encodes KCa1.1 channels (also called big potassium channels), were significantly lower in the membrane fraction and higher in the cytosolic fraction of patient cells than normal cells. When patient cells were exposed to 50 mM potassium buffer, which was used to induce depolarization, the altered subcellular distribution of BK channels remained unchanged. Conclusion These findings suggest a novel mechanism for the development of hypokalemia and paralysis in HOKPP and demonstrate a connection between disease-associated mutations in calcium/sodium channels and pathogenic changes in nonmutant potassium channels. PMID:25379045

Kim, Sung-Jo; Kang, Sun-Yang; Yi, Jin Woong; Kim, Seung-Min

2014-01-01

185

Identification of Novel Mutations Causing Familial Primary Congenital Glaucoma in Indian Pedigrees  

Microsoft Academic Search

PURPOSE. To determine the possible molecular genetic defect underlying primary congenital glaucoma (PCG) in India and to identify the pathogenic mutations causing this childhood blind- ness. METHODS. Twenty-two members of five clinically well-charac- terized consanguineous families were studied. The primary candidate gene CYP1B1 was amplified from genomic DNA, sequenced, and analyzed in control subjects and patients to identify the disease-causing

Shirly G. Panicker; Aramati B. M. Reddy; Anil K. Mandal; Niyaz Ahmed; Hampapathalu A. Nagarajaram; Seyed E. Hasnain; Dorairajan Balasubramanian

186

Compound Heterozygosity for Two Novel SLC26A4 Mutations in a Large Iranian Pedigree with Pendred Syndrome  

PubMed Central

Objectives The aim of this study was to detect the genetic cause of deafness in a large Iranian family. Due to the importance of SLC26A4 in causing hearing loss, information about the gene mutations can be beneficial in molecular detection and management of deaf patients. Methods We investigated the genetic etiology in a large consanguineous family with 9 deaf patients from Fars province of Iran with no GJB2 mutations. Initially, linkage analysis was performed by four DFNB4 short tandem repeat markers. The result showed linkage to DFNB4 locus. Following that, DNA sequencing of all 21 exons, their adjacent intronic sequences and the promoter of SLC26A4 was carried out for mutation detection. Results Two novel mutations (c.863-864insT and c.881-882delAC) were identified in exon 7 of the gene, in both homozygous and compound heterozygous state in patients. Conclusion Our results supported the importance of the SLC26A4 mutations in the etiology of hearing loss among the Iranian patients and therefore its mutation screening should be considered after GJB2 in the molecular diagnostics of hearing loss, especially when enlarged vestibular aqueduct or goiter is detected. PMID:24353858

Yazdanpanahi, Nasrin; Tabatabaiefar, Mohammad Amin; Farrokhi, Effat; Abdian, Narges; Bagheri, Nader; Shahbazi, Shirin; Noormohammadi, Zahra

2013-01-01

187

Characterization of a novel missense mutation in the prodomain of GDF5, which underlies brachydactyly type C and mild Grebe type chondrodysplasia in a large Pakistani family.  

PubMed

All TGF-beta family members have a prodomain that is important for secretion. Lack of secretion of a TGF-beta family member GDF5 is known to underlie some skeletal abnormalities, such as brachydactyly type C that is characterized by a huge and unexplained phenotypic variability. To search for potential phenotypic modifiers regulating secretion of GDF5, we compared cells overexpressing wild type (Wt) GDF5 and GDF5 with a novel mutation in the prodomain identified in a large Pakistani family with Brachydactyly type C and mild Grebe type chondrodyslplasia (c527T>C; p.Leu176Pro). Initial in vitro expression studies revealed that the p.Leu176Pro mutant (Mut) GDF5 was not secreted outside the cells. We subsequently showed that GDF5 was capable of forming a complex with latent transforming growth factor binding proteins, LTBP1 and LTBP2. Furthermore, secretion of LTBP1 and LTBP2 was severely impaired in cells expressing the Mut-GDF5 compared to Wt-GDF5. Finally, we demonstrated that secretion of Wt-GDF5 was inhibited by the Mut-GDF5, but only when LTBP (LTBP1 or LTBP2) was co-expressed. Based on these findings, we suggest a novel model, where the dosage of secretory co-factors or stabilizing proteins like LTBP1 and LTBP2 in the microenvironment may affect the extent of GDF5 secretion and thereby function as modifiers in phenotypes caused by GDF5 mutations. PMID:23812741

Farooq, Muhammad; Nakai, Hiroyuki; Fujimoto, Atsushi; Fujikawa, Hiroki; Kjaer, Klaus Wilbrandt; Baig, Shahid Mahmood; Shimomura, Yutaka

2013-11-01

188

The ATL gene family from Arabidopsis thaliana and Oryza sativa comprises a large number of putative ubiquitin ligases of the RING-H2 type.  

PubMed

Ubiquitin ligases play an important regulatory role in the control of protein degradation processes via the ubiquitin/26S proteasome pathway in eukaryotes. These enzymes participate in substrate specification and mediate the transfer of ubiquitin to target proteins. A large number of ubiquitin ligases are predicted in the eukaryotes whose genomes have been sequenced; in Arabidopsis thaliana more than 1300 genes are thought to encode ubiquitin ligases. At least three classes of ubiquitin ligases are present in Arabidopsis, one of which comprises about 470 RING zinc-finger domain proteins. Within this class we have characterized the ATL family that encodes a RING-H2 finger. We identified 80 members of this family in A. thaliana and 121 in Oryza sativa. About 60% of the rice ATLs are clustered with A. thaliana ATLs, and in many cases the gene products showed sequence similarities beyond the ATL's conserved features, suggesting that they could be orthologous genes. Ninety percent of the ATLs are intronless genes, suggesting that the structure of the basic ATL protein may have evolved as a functional module. We carried out a survey of T-DNA insertions in 30% of the Arabidopsis ATL genes and screened for possible phenotypes. Four of these genes are likely to be essential for viability, since homozygous plants for the T-DNA insertion were not recovered. One of them, ATL8, is mainly expressed in young siliques, suggesting a role during embryogenesis. We also recovered a line carrying a T-DNA insertion in ATL43 that showed an ABA-insensitive phenotype, suggesting a role of this gene in the ABA response. The organization of ATLs in Arabidopsis and rice in this study will be a valuable comprehensive guide for this multigene family. PMID:16557337

Serrano, Mario; Parra, Socorro; Alcaraz, Luis D; Guzmán, Plinio

2006-04-01

189

Comparison of autoantibody specificities between traditional and bead-based assays in a large, diverse collection of SLE patients and family members  

PubMed Central

Objective The replacement of standard immunofluorescence anti-nuclear antibody (ANA) methods with bead-based assays is a new clinical option. A large, multi-racial cohort of SLE patients, blood relatives and unaffected control individuals was evaluated for familial aggregation and subset clustering of autoantibodies by high-throughput serum screening technology and traditional methods. Methods Serum samples (1,540 SLE patients, 1,127 unaffected relatives, and 906 healthy, population-based controls) were analyzed for SLE autoantibodies using a bead-based assay, immunofluorescence, and immunodiffusion. Autoantibody prevalence, disease sensitivity, clustering, and association with standard immunodiffusion results were evaluated. Results ANA frequency in SLE patient sera were 89%, 73%, and 67% by BioPlex 2200 and 94%, 84%, and 86% by immunofluorescence in African-American, Hispanic, and European-American patients respectively. 60kD Ro, La, Sm, nRNP A, and ribosomal P prevalence were compared across assays, with sensitivities ranging from 0.92 to 0.83 and specificities ranging from 0.90 to 0.79. Cluster autoantibody analysis showed association of three subsets: 1) 60kD Ro, 52kD Ro and La, 2) spliceosomal proteins, and 3) dsDNA, chromatin, and ribosomal P. Familial aggregation of Sm/RNP, ribosomal P, and 60kD Ro in SLE patient sibling pairs was observed (p ? 0.004). Simplex pedigree patients had a greater prevalence for dsDNA (p=0.0003) and chromatin (p=0.005) autoantibodies than multiplex patients. Conclusion ANA frequencies detected by a bead-based assay are lower in European-American SLE patients compared to immunofluorescence. These assays have strong positive predictive values across racial groups, provide useful information for clinical care, and provide unique insights to familial aggregation and autoantibody clustering. PMID:23112091

Bruner, Benjamin F.; Guthridge, Joel M.; Lu, Rufei; Vidal, Gabriel; Kelly, Jennifer A.; Robertson, Julie M.; Kamen, Diane L.; Gilkeson, Gary S.; Neas, Barbara R.; Reichlin, Morris; Scofield, R. Hal; Harley, John B.; James, Judith A.

2012-01-01

190

Identification of Rare Recurrent Copy Number Variants in High-Risk Autism Families and Their Prevalence in a Large ASD Population  

PubMed Central

Structural variation is thought to play a major etiological role in the development of autism spectrum disorders (ASDs), and numerous studies documenting the relevance of copy number variants (CNVs) in ASD have been published since 2006. To determine if large ASD families harbor high-impact CNVs that may have broader impact in the general ASD population, we used the Affymetrix genome-wide human SNP array 6.0 to identify 153 putative autism-specific CNVs present in 55 individuals with ASD from 9 multiplex ASD pedigrees. To evaluate the actual prevalence of these CNVs as well as 185 CNVs reportedly associated with ASD from published studies many of which are insufficiently powered, we designed a custom Illumina array and used it to interrogate these CNVs in 3,000 ASD cases and 6,000 controls. Additional single nucleotide variants (SNVs) on the array identified 25 CNVs that we did not detect in our family studies at the standard SNP array resolution. After molecular validation, our results demonstrated that 15 CNVs identified in high-risk ASD families also were found in two or more ASD cases with odds ratios greater than 2.0, strengthening their support as ASD risk variants. In addition, of the 25 CNVs identified using SNV probes on our custom array, 9 also had odds ratios greater than 2.0, suggesting that these CNVs also are ASD risk variants. Eighteen of the validated CNVs have not been reported previously in individuals with ASD and three have only been observed once. Finally, we confirmed the association of 31 of 185 published ASD-associated CNVs in our dataset with odds ratios greater than 2.0, suggesting they may be of clinical relevance in the evaluation of children with ASDs. Taken together, these data provide strong support for the existence and application of high-impact CNVs in the clinical genetic evaluation of children with ASD. PMID:23341896

Christensen, G. Bryce; Kim, Cecilia; Frackelton, Edward; Thomas, Kelly; da Silva, Renata Pellegrino; Stevens, Jeff; Baird, Lisa; Otterud, Brith; Ho, Karen; Varvil, Tena; Leppert, Tami; Lambert, Christophe G.; Leppert, Mark; Hakonarson, Hakon

2013-01-01

191

A rare branch-point mutation is associated with missplicing of fibrillin-2 in a large family with congenital contractural arachnodactyly.  

PubMed

Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to but genetically distinct from Marfan syndrome. Genetic-linkage analysis has implicated the fibrillin-2 gene (FBN2) as the CCA locus. Mutation analysis of two isolated CCA patients revealed missense mutations, indicating that defects in FBN2 may be responsible for this disorder. However, cosegregation of a mutant allele with the disease phenotype has not yet been established. We have investigated the primary cause of CCA in a large well-characterized kindred with five generations comprising 18 affected individuals. Previous studies demonstrated linkage of this family's CCA phenotype to FBN2. Mutation analysis of cDNA derived from the proband and her affected brother, using a nonisotopic RNase cleavage assay, revealed the partial skipping of exon 31. Approximately 25% mutant transcript is produced, which is apparently sufficient to cause a CCA phenotype. Sequence analysis of genomic DNA revealed an unusual base composition for intron 30 and identified the mutation, a g-26t transversion, in the vicinity of the splicing branch-point site in intron 30. Genomic DNA from 30 additional family members, both affected and unaffected, then was analyzed for the mutation. The results clearly demonstrate cosegregation of the branch-point mutation with the CCA phenotype. This is the first report of a CCA mutation in a multiplex family, unequivocally establishing that mutation in FBN2 are responsible for the CCA phenotype. In addition, branch-point mutations only very rarely have been associated with human disease, suggesting that the unusual composition of this intron influences splicing stability. PMID:9199560

Maslen, C; Babcock, D; Raghunath, M; Steinmann, B

1997-06-01

192

A Homozygous CARD9 Mutation in a Family with Susceptibility to Fungal Infections  

PubMed Central

BACKGROUND Chronic mucocutaneous candidiasis may be manifested as a primary immunodeficiency characterized by persistent or recurrent infections of the mucosa or the skin with candida species. Most cases are sporadic, but both autosomal dominant inheritance and autosomal recessive inheritance have been described. METHODS We performed genetic studies in 36 members of a large, consanguineous five-generation family, in which 4 members had recurrent fungal infections and an additional 3 members died during adolescence, 2 after invasive infection of the brain with candida species. All 36 family members were enrolled in the study, and 22 had blood samples taken for DNA analysis. Homozygosity mapping was used to locate the mutated gene. In the 4 affected family members (patients) and the 18 unaffected members we sequenced CARD9, the gene encoding the caspase recruitment domain-containing protein 9, carried out T-cell phenotyping, and performed functional studies, with the use of either leukocytes from the patients or a reconstituted murine model of the genetic defect. RESULTS We found linkage (lod score, 3.6) to a genomic interval on chromosome 9q, including CARD9. All four patients had a homozygous point mutation in CARD9, resulting in a premature termination codon (Q295X). Healthy family members had wild-type expression of the CARD9 protein; the four patients lacked wild-type expression, which was associated with low numbers of Th17 cells (helper T cells producing interleukin-17). Functional studies based on genetic reconstitution of myeloid cells from Card9?/? mice showed that the Q295X mutation impairs innate signaling from the antifungal pattern-recognition receptor dectin-1. CONCLUSIONS An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis is associated with homozygous mutations in CARD9. PMID:19864672

Glocker, Erik-Oliver; Hennigs, Andre; Nabavi, Mohammad; Schaffer, Alejandro A.; Woellner, Cristina; Salzer, Ulrich; Pfeifer, Dietmar; Veelken, Hendrik; Warnatz, Klaus; Tahami, Fariba; Jamal, Sarah; Manguiat, Annabelle; Rezaei, Nima; Amirzargar, Ali Akbar; Plebani, Alessandro; Hannesschlager, Nicole; Gross, Olaf; Ruland, Jurgen; Grimbacher, Bodo

2009-01-01

193

The vertebrate makorin ubiquitin ligase gene family has been shaped by large-scale duplication and retroposition from an ancestral gonad-specific, maternal-effect gene  

PubMed Central

Background Members of the makorin (mkrn) gene family encode RING/C3H zinc finger proteins with U3 ubiquitin ligase activity. Although these proteins have been described in a variety of eukaryotes such as plants, fungi, invertebrates and vertebrates including human, almost nothing is known about their structural and functional evolution. Results Via partial sequencing of a testis cDNA library from the poeciliid fish Xiphophorus maculatus, we have identified a new member of the makorin gene family, that we called mkrn4. In addition to the already described mkrn1 and mkrn2, mkrn4 is the third example of a makorin gene present in both tetrapods and ray-finned fish. However, this gene was not detected in mouse and rat, suggesting its loss in the lineage leading to rodent murids. Mkrn2 and mkrn4 are located in large ancient duplicated regions in tetrapod and fish genomes, suggesting the possible involvement of ancestral vertebrate-specific genome duplication in the formation of these genes. Intriguingly, many mkrn1 and mkrn2 intronless retrocopies have been detected in mammals but not in other vertebrates, most of them corresponding to pseudogenes. The nature and number of zinc fingers were found to be conserved in Mkrn1 and Mkrn2 but much more variable in Mkrn4, with lineage-specific differences. RT-qPCR analysis demonstrated a highly gonad-biased expression pattern for makorin genes in medaka and zebrafish (ray-finned fishes) and amphibians, but a strong relaxation of this specificity in birds and mammals. All three mkrn genes were maternally expressed before zygotic genome activation in both medaka and zebrafish early embryos. Conclusion Our analysis demonstrates that the makorin gene family has evolved through large-scale duplication and subsequent lineage-specific retroposition-mediated duplications in vertebrates. From the three major vertebrate mkrn genes, mkrn4 shows the highest evolutionary dynamics, with lineage-specific loss of zinc fingers and even complete gene elimination from certain groups of vertebrates. Comparative expression analysis strongly suggests that the ancestral E3 ubiquitin ligase function of the single copy mkrn gene before duplication in vertebrates was gonad-specific, with maternal expression in early embryos. PMID:21172006

2010-01-01

194

CD3G Gene Defects in Familial Autoimmune Thyroiditis.  

PubMed

The patients with CD3? deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCR??+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations. PMID:24910257

Gokturk, B; Keles, S; Kirac, M; Artac, H; Tokgoz, H; Guner, S N; Caliskan, U; Caliskaner, Z; van der Burg, M; van Dongen, J; Morgan, N V; Reisli, I

2014-11-01

195

Congenital myopathies in Israeli families.  

PubMed

The clinical features of 37 patients from 32 Israeli families with congenital myopathies evaluated between 1983 and 2004 are described: 13 children were diagnosed with congenital fiber type disproportion, 10 had myotubular myopathy, 7 had nemaline myopathy, 5 had central core disease, 1 had actin myopathy, and 1 had multi-minicore disease. There were 7 families (22%) that had parental consanguinity, and 4 families (12%) had more than 1 patient with congenital myopathy. Of the patients, 31 (84%) presented with clinical symptoms before 4 months of age, and 6 children (16%) presented after 1 year of age. Thirteen children (35%) had a severe phenotype with chronic ventilatory dependence or mortality before the age of 11 years. Facial weakness was associated with a severe phenotype. There was a high rate of a severe clinical phenotype in patients with myotubular myopathy (60%) and in patients with nemaline myopathy (57%), whereas in patients with congenital fiber type disproportion and in patients with central core disease, the proportion of a severe phenotype was lower (23% and 0%, respectively). PMID:17641259

Weiss, Karin; Shapira, Yehuda; Glick, Benjamin; Lerman-Sagie, Tally; Shahar, Eli; Goez, Helly; Kutai, Miriam; Nevo, Yoram

2007-06-01

196

Comparative Analysis of P450 Signature Motifs EXXR and CXG in the Large and Diverse Kingdom of Fungi: Identification of Evolutionarily Conserved Amino Acid Patterns Characteristic of P450 Family  

PubMed Central

Cytochrome P450 monooxygenases (P450s) are heme-thiolate proteins distributed across the biological kingdoms. P450s are catalytically versatile and play key roles in organisms primary and secondary metabolism. Identification of P450s across the biological kingdoms depends largely on the identification of two P450 signature motifs, EXXR and CXG, in the protein sequence. Once a putative protein has been identified as P450, it will be assigned to a family and subfamily based on the criteria that P450s within a family share more than 40% homology and members of subfamilies share more than 55% homology. However, to date, no evidence has been presented that can distinguish members of a P450 family. Here, for the first time we report the identification of EXXR- and CXG-motifs-based amino acid patterns that are characteristic of the P450 family. Analysis of P450 signature motifs in the under-explored fungal P450s from four different phyla, ascomycota, basidiomycota, zygomycota and chytridiomycota, indicated that the EXXR motif is highly variable and the CXG motif is somewhat variable. The amino acids threonine and leucine are preferred as second and third amino acids in the EXXR motif and proline and glycine are preferred as second and third amino acids in the CXG motif in fungal P450s. Analysis of 67 P450 families from biological kingdoms such as plants, animals, bacteria and fungi showed conservation of a set of amino acid patterns characteristic of a particular P450 family in EXXR and CXG motifs. This suggests that during the divergence of P450 families from a common ancestor these amino acids patterns evolve and are retained in each P450 family as a signature of that family. The role of amino acid patterns characteristic of a P450 family in the structural and/or functional aspects of members of the P450 family is a topic for future research. PMID:24743800

Syed, Khajamohiddin; Mashele, Samson Sitheni

2014-01-01

197

IFT27, encoding a small GTPase component of IFT particles, is mutated in a consanguineous family with Bardet-Biedl syndrome.  

PubMed

Bardet-Biedl syndrome (BBS) is an autosomal recessive ciliopathy with multisystem involvement. So far, 18 BBS genes have been identified and the majority of them are essential for the function of BBSome, a protein complex involved in transporting membrane proteins into and from cilia. Yet defects in the identified genes cannot account for all the BBS cases. The genetic heterogeneity of this disease poses significant challenge to the identification of additional BBS genes. In this study, we coupled human genetics with functional validation in zebrafish and identified IFT27 as a novel BBS gene (BBS19). This is the first time an intraflagellar transport (IFT) gene is implicated in the pathogenesis of BBS, highlighting the genetic complexity of this disease. PMID:24488770

Aldahmesh, Mohammed A; Li, Yuanyuan; Alhashem, Amal; Anazi, Shams; Alkuraya, Hisham; Hashem, Mais; Awaji, Ali A; Sogaty, Sameera; Alkharashi, Abdullah; Alzahrani, Saeed; Al Hazzaa, Selwa A; Xiong, Yong; Kong, Shanshan; Sun, Zhaoxia; Alkuraya, Fowzan S

2014-06-15

198

The phenotype of a CASQ2 mutation in a Saudi family with catecholaminergic polymorphic ventricular tachycardia.  

PubMed

Catecholaminergic polymorphic ventricular tachycardia (CPVT) manifests with episodic syncope or sudden death in young patients following physical activity or emotional stress. The autosomal recessive form of CPVT is caused by mutations in the CASQ2 gene. In a consanguineous family, a novel homozygous CASQ2 mutation (p.L77P) was identified in a child with CPVT who required implantation of a cardioverter defibrillator due to episodes of syncope while on medical therapy. Genetic testing found the younger sibling, who had normal initial clinical screening, to be affected. Our cases underscore the importance of family screening through genetic testing to preemptively apply the appropriate medical intervention in CPVT. PMID:22650415

Al-Hassnan, Zuhair N; Tulbah, Sahar; Al-Manea, Waleed; Al-Fayyadh, Majid

2013-05-01

199

An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation  

Microsoft Academic Search

Cerebral palsy (CP) is defined as any nonprogressive motor deficits resulting from cerebral abnormalities that occur in the prenatal or perinatal period. Symptoms become apparent during the first year of life. Genetic forms of CP account for about 2% in European populations but are thought to cause a substantial proportion in consanguineous families. We have identified a large consanguineous family

Anna Rajab; Seung-Yun Yoo; Aiman Abdulgalil; Salem Kathiri; Riaz Ahmed; Ganeshwaran H. Mochida; Adria Bodell; A. James Barkovich; Christopher A. Walsh

2006-01-01

200

Identification of a New Intronic BMPR2-Mutation and Early Diagnosis of Heritable Pulmonary Arterial Hypertension in a Large Family with Mean Clinical Follow-Up of 12 Years  

PubMed Central

Background Mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene can lead to hereditary pulmonary arterial hypertension (HPAH) and are detected in more than 80% of cases with familial aggregation of the disease. Factors determining disease penetrance are largely unknown. Methods A mean clinical follow-up of 12 years was accomplished in 46 family members including echocardiography, stress-Dopplerechocardiography and genetic analysis of TGF-? pathway genes. Right heart catheterization and RNA-analysis was performed in members with pathological findings. Results Manifest HPAH was diagnosed in 8 members, 4 were already deceased, two died during the follow-up, two are still alive. Normal pulmonary artery systolic pressure at rest but hypertensive response to exercise has been identified in 19 family members. Analysis of BMPR2 transcripts revealed aberrant splicing due to an insertion of an intronic Alu element adjacent to exon 6. All HPAH patients and 12 further asymptomatic family members carried this insertion. During follow-up two family members carrying hypertensive response and the Alu insertion developed manifest HPAH. Conclusion This is the first report of an intronic BMPR2 mutation due to an Alu element insertion causing HPAH in a large family which has been confirmed on RNA-level. Only those members that carried both hypertensive response and the mutation developed manifest HPAH during follow-up. Our findings highlight the importance of including further methods such as RNA analysis into the molecular genetic diagnostic of PAH patients. They suggest that at least in some families hypertensive response may be an additional risk factor for disease manifestation and penetrance. PMID:24621962

Pfarr, Nicole; Szamalek-Hoegel, Justyna; Lichtblau, Mona; Nagel, Christian; Egenlauf, Benjamin; Ehlken, Nicola; Grunig, Ekkehard

2014-01-01

201

Variable Myopathic Presentation in a Single Family with Novel Skeletal RYR1 Mutation  

PubMed Central

We describe an autosomal recessive heterogeneous congenital myopathy in a large consanguineous family. The disease is characterized by variable severity, progressive course in 3 of 4 patients, myopathic face without ophthalmoplegia and proximal muscle weakness. Absence of cores was noted in all patients. Genome wide linkage analysis revealed a single locus on chromosome 19q13 with Zmax?=?3.86 at ??=?0.0 and homozygosity of the polymorphic markers at this locus in patients. Direct sequencing of the main candidate gene within the candidate region, RYR1, was performed. A novel homozygous A to G nucleotide substitution (p.Y3016C) within exon 60 of the RYR1 gene was found in patients. ARMS PCR was used to screen for the mutation in all available family members and in an additional 150 healthy individuals. This procedure confirmed sequence analysis and did not reveal the A to G mutation (p.Y3016C) in 300 chromosomes from healthy individuals. Functional analysis on EBV immortalized cell lines showed no effect of the mutation on RyR1 pharmacological activation or the content of intracellular Ca2+ stores. Western blot analysis demonstrated a significant reduction of the RyR1 protein in the patient’s muscle concomitant with a reduction of the DHPR?1.1 protein. This novel mutation resulting in RyR1 protein decrease causes heterogeneous clinical presentation, including slow progression course and absence of centrally localized cores on muscle biopsy. We suggest that RYR1 related myopathy should be considered in a wide variety of clinical and pathological presentation in childhood myopathies. PMID:23894444

Rokach, Ori; Becker Cohen, Michal; Fellig, Yakov; Straussberg, Rachel; Dor, Talya; Daana, Muhannad; Mitrani-Rosenbaum, Stella; Nevo, Yoram

2013-01-01

202

Autosomal dominant Kufs` disease: Clinical heterogeneity in nine families, and exclusion of linkage to CLN1 and CLN3 markers in a large American kindred  

SciTech Connect

Most forms of neuronal ceroid lipofuscinosis (NCL) are autosomal recessive, and three genes have already been mapped: the infantile form (CLN 1); the juvenile form (CLN 3); and the early juvenile variant (CLN 5) on chromosomes 1, 16 and 13, respectively. Kufs` disease or adolescent-adult onset NCL is usually inherited as an autosomal recessive trait, and presents as three distinct clinical syndromes: progressive myoclonus epilepsy (PME) with onset in the early teens or around age 30; and onset of dementia with motor disability in the 30s. We have studied three families originating from different parts of the USA manifesting dominantly inherited Kufs` disease. Granular osmophilic deposits (GROD) were found in brain, but storage in skin was not an obligatory feature. Six dominantly inherited PME families have been ascertained from three different regions of Spain. No storage was found in skin or muscle in any of these families. The mean age of onset in the American families is earlier, the clinical manifestations more severe, and the progression much more rapid that in the Spanish families. These findings would suggest the possibility of genetic heterogeneity involving two or more loci, or different mutations at the same gene locus. Genetic linkage studies have been carried out in a six-generation New Jersey family in an attempt to characterize the gene(s) responsible for this disorder. The infantile NCL locus on chromosome 1p (CLN1) and the juvenile NCL locus on chromosome 16p (CLN 3) have been excluded in this family. Further clinical, pathological and molecular genetic studies should lead to the clarification of the diagnostic approaches in this disorder.

Andermann, F.; Andermann, E.; Carpenter, S. [and others

1994-09-01

203

Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families: Implications for genetic testing  

PubMed Central

AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplification (MLPA). RESULTS: Eighteen germline mutations (50%) were identified, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the definite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam I/II criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family. CONCLUSION: Our study describes for the first time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population. PMID:17569143

Papp, Janos; Kovacs, Marietta E; Olah, Edith

2007-01-01

204

Cloning and sequencing of thiol-specific antioxidant from mammalian brain: Alkyl hydroperoxide reductase and thiol-specific antioxidant define a large family of antioxidant enzymes  

SciTech Connect

A cDNA corresponding to a thiol-specific antioxidant enzyme (TSA) was isolated from a rat brain cDNA library with the use of antibodies to bovine TSA. The cDNA clone encoded an open reading frame capable of encoding a 198-residue polypeptide. The rat and yeast TSA proteins show significant sequence homology to the 21-kDa component (AhpC) of Salmonella typhimurium alkyl hydroperoxide reductase, and we have found that AhpC exhibits TSA activity. AhpC and TSA define a family of >25 different proteins present in organisms from all kingdoms. The similarity among the family members extends over the entire sequence and ranges between 23% and 98% identity. A majority of the members of the AhpC/TSA family contain two conserved cysteines. At least eight of the genes encoding AhpC/TSA-like polypeptides are found in proximity to genes encoding other oxidoreductase activities, and the expression of several of the homologs has been correlated with pathogenicity. The authors suggest that the AhpC/TSA family represents a widely distributed class of antioxidant enzymes. They also report that a second family of proteins, defined by the 57-kDa component (AhpF) of alkyl hydroperoxide reductase and by thioredoxin reductase, has expanded to include six additional members.

Chae, H.Z; Storz, G.; Rhee, S.G. [National Institutes of Health, Bethesda, MD (United States); Robison, K.; Church, G. [Harvard Medical School, Boston, MA (United States); Poole, L.B. [Bowman Gray School of Medicine of Wake Forest Univ., Winstom-Salem, NC (United States)

1994-07-19

205

The Quality of Teachers' Interactive Conversations with Preschool Children from Low-Income Families during Small-Group and Large-Group Activities  

ERIC Educational Resources Information Center

This study examined the quality of preschool teachers' interactive conversations with three- and four-year-olds in two Head Start classrooms serving children from low-income families in the United States. Over a period of 20?weeks, 10 bi-weekly observations of conversations (totaling 15?h per classroom) were conducted in one small-group (Play…

Chen, Jennifer J.; de Groot Kim, Sonja

2014-01-01

206

Familiality of Tourette Syndrome, Obsessive-Compulsive Disorder, and Attention-Deficit/Hyperactivity Disorder: Heritability Analysis in a Large Sib-Pair Sample  

ERIC Educational Resources Information Center

Objective: Tourette syndrome (TS) is a neuropsychiatric disorder with a genetic component that is highly comorbid with obsessive-compulsive disorder (OCD) and attention deficit/hyperactivity disorder (ADHD). However, the genetic relations between these disorders have not been clearly elucidated. This study examined the familial relations among TS,…

Mathews, Carol A.; Grados, Marco A.

2011-01-01

207

Attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members and the general population in a large city in Guangzhou, China  

PubMed Central

Purpose Stigma towards people with mental illness is believed to be widespread in low and middle income countries. Methods This study assessed the attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members of patients in a psychiatric facility and the general public using a standard 43-item survey (N?=?535). Exploratory factor analysis identified four distinctive attitudes which were then compared using Analysis of Covariance (ANCOVA) among the four groups, all with ties to the largest psychiatric facility in Guangzhou, China, adjusting for sociodemographic differences. Results Four uncorrelated factors expressed preferences for 1) community-based treatment, social integration and a biopsychosocial model of causation, 2) direct personal relationships with people with mental illness, 3) a lack of fear and positive views of personal interactions with people with mental illness, 4) disbelief in superstitious explanations of mental illness. Statistically significant differences favored community-based treatment and biopsychosocial causation (factor 1) among professional groups (psychiatrists and nurses) as compared with family members and the general public (p?family members, unexpectedly, showed far weaker personal preferences for direct personal relationships with people with mental illness than all three other groups (p?family members showed the least positive attitudes towards direct personal relationships with people with mental illness. These findings suggest support for a more extensive, formal system of care that gives family members some distance from the problems of their relatives and support in their care. PMID:25053975

2014-01-01

208

The relationship between family history, gender role attitudes, and susceptibility to gender inequitable perceptions of family and family member functioning  

Microsoft Academic Search

This research examined how family roles, gender of family leadership, beliefs about the consequences of maternal employment, and family history of parental division of responsibility related to young adults' perceptions of family and individual family member functioning. One hundred seven (107), predominantly Anglo American undergraduate students completing courses in educational psychology at a large midwestern university rated two videotaped family

David C. Ivey; Tamara Yaktus

1996-01-01

209

Linkage Mapping and Whole Exome Sequencing Identify a Shared Variant in CX3CR1 in a Large Multi-Generation Family.  

PubMed

Developmental dysplasia of the hip (DDH) is a crippling condition that affects children and adults, with an average incidence of 1-1.5 cases per 1000 live births. It results in disabling arthritis of the hip in up to 60% patients in the 20-40year age group. There is no accurate diagnostic test available for newborns. The purpose of our study is to develop a sensitive and specific genetic test for DDH by identifying causative mutations. Linkage analysis and whole exome sequencing of 4 severely affected individuals of a 4 generation 71 member family was performed. The damaging rs3732378 variant in the CX3CR1 chemokine receptor was shared by all affected family members and by 15% of 28 sporadic dysplastics. PMID:24998320

Feldman, George J; Parvizi, Javad; Sawan, Hind; Erickson, Jill A; Peters, Christopher L

2014-09-01

210

Two large Arabidopsis thaliana gene families are homologous to the Brassica gene superfamily that encodes pollen coat proteins and the male component of the self-incompatibility response  

Microsoft Academic Search

The male component of the self-incompatibility response in Brassica has recently been shown to be encoded by the S locus cysteine-rich gene (SCR). SCR is related, at the sequence level, to the pollen coat protein (PCP) gene family whose members encode small, cysteine-rich proteins located in the proteo-lipidic surface layer (tryphine) of Brassica pollen grains. Here we show that the

Vincent Vanoosthuyse; Christine Miege; Christian Dumas; J. Mark Cock

2001-01-01

211

A novel stop mutation truncating critical regions of the cardiac transcription factor NKX2-5 in a large family with autosomaldominant inherited congenital heart disease  

Microsoft Academic Search

We report on a familial screen of five female members in three generations affected by an autosomal-dominant inherited atrioventricular\\u000a (AV) conduction block associated with atrial septal defects (ASD) and other congenital cardiovascular diseases (CCVD), such\\u000a as pulmonary artery stenosis (PAS), patent foramen ovale (PFO) and ventricular septal defect (VSD). We tested the cardiac\\u000a transcription factor NKX2-5 which is known to

S. Pabst; B. Wollnik; E. Rohmann; Y. Hintz; K. Glänzer; H. Vetter; G. Nickenig; Christian Grohé

2008-01-01

212

Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma.  

PubMed

Charcot-Marie-Tooth disease (CMT) with autosomal recessive (AR) inheritance is a heterogeneous group of inherited motor and sensory neuropathies. In some families from Japan and Brazil, a demyelinating CMT, mainly characterized by the presence of myelin outfoldings on nerve biopsies, cosegregated as an autosomal recessive trait with early-onset glaucoma. We identified two such large consanguineous families from Tunisia and Morocco with ages at onset ranging from 2 to 15 years. We mapped this syndrome to chromosome 11p15, in a 4.6-cM region overlapping the locus for an isolated demyelinating ARCMT (CMT4B2). In these two families, we identified two different nonsense mutations in the myotubularin-related 13 gene, MTMR13. The MTMR protein family includes proteins with a phosphoinositide phosphatase activity, as well as proteins in which key catalytic residues are missing and that are thus called "pseudophosphatases." MTM1, the first identified member of this family, and MTMR2 are responsible for X-linked myotubular myopathy and Charcot-Marie-Tooth disease type 4B1, an isolated peripheral neuropathy with myelin outfoldings, respectively. Both encode active phosphatases. It is striking to note that mutations in MTMR13 also cause peripheral neuropathy with myelin outfoldings, although it belongs to a pseudophosphatase subgroup, since its closest homologue is MTMR5/Sbf1. This is the first human disease caused by mutation in a pseudophosphatase, emphasizing the important function of these putatively inactive enzymes. MTMR13 may be important for the development of both the peripheral nerves and the trabeculum meshwork, which permits the outflow of the aqueous humor. Both of these tissues have the same embryonic origin. PMID:12687498

Azzedine, H; Bolino, A; Taïeb, T; Birouk, N; Di Duca, M; Bouhouche, A; Benamou, S; Mrabet, A; Hammadouche, T; Chkili, T; Gouider, R; Ravazzolo, R; Brice, A; Laporte, J; LeGuern, E

2003-05-01

213

Family Literacy: Exploring Family Practices.  

ERIC Educational Resources Information Center

Reviews literature on family influence on children's acquisition of literacy. Discusses the ambivalence regarding family literacy theories and the lack of family literacy theoretical frameworks. Identifies types of family involvement and effective literacy strategies for families. Finds that most studies suggest that family literacy contributes to…

Saracho, Olivia N.

2002-01-01

214

Familial idiopathic small-bowel and colonic varices in three siblings.  

PubMed

Idiopathic small-bowel and colonic varices are a rare source of bleeding from the gastrointestinal tract. To date there are only eight published case series of familial idiopathic small-bowel and colonic varices. We present a case series detailing three affected siblings who presented with significant lower gastrointestinal bleeding and had multiple varices on endoscopy and imaging. Though not confirmed, consanguinity in the parents suggests an autosomal recessive mode of inheritance. We summarize the literature to date and describe our institution's experience of endoscopy, diagnostic imaging, and treatment in these patients. PMID:25036657

Boland, Paul; Leonard, Jennifer; Saunders, Michael; Bursey, Ford

2014-10-01

215

A splice site mutation in the methyltransferase gene FTSJ1 in Xp11.23 is associated with non-syndromic mental retardation in a large Belgian family (MRX9).  

PubMed

Mental retardation is the most frequent cause of serious handicap in children and young adults. The underlying causes of this heterogeneous condition are both acquired and genetically based. A recently performed refinement of the linkage interval in a large Belgian family with mild to severe non-syndromic X linked mental retardation, classified as MRX9, revealed a candidate region of 11.3 Mb between markers DXS228 and DXS1204 on the short arm of the X chromosome. In order to identify the underlying disease gene in the MRX9 family, we established a gene catalogue for the candidate region and performed comprehensive mutation analysis by direct sequencing. A human homologue of the bacterial 23S rRNA methyltransferase Fstj, the FTSJ1 gene, is located within this region and displayed a sequence alteration in the conserved acceptor splice site of intron 3 (IVS3-2A>G) in all tested patients and carrier females of this family. In contrast, it was absent in all unaffected male family members tested. The mutation results in skipping of exon 4 and introduces a premature stop codon in exon 5, probably leading to a severely truncated protein. Our finding indicates that a protein, possibly associated with ribosomal stability, can be linked to X linked mental retardation (XLMR). PMID:15342698

Ramser, J; Winnepenninckx, B; Lenski, C; Errijgers, V; Platzer, M; Schwartz, C E; Meindl, A; Kooy, R F

2004-09-01

216

Family studies in common variable immunodeficiency.  

PubMed

The occurrence of cancer, immunodeficiency, and diseases with possible autoimmune aetiology were studied in 355 blood relatives of 12 patients with common variable immunodeficiency (CVID). The family members were identified through the patients and interviewed after completing a questionnaire, their diseases were medically confirmed by local general practitioners. In two families consanguineous marriages were identified with the coefficients of inbreeding of 0.03125 and 0.01563, respectively: one patient, a dizygotic twin of an unaffected sister, was a granddaughter of first cousins, the second patient was the third daughter of second cousins. These cases of CVID strongly support the autosomal recessivity of the underlying genes. One male patient with CVID was shown to be related to a patient with X-linked hypogammaglobulinaemia, both sharing a common carrier. The different clinical courses of their diseases suggest two genetically determined immunodeficiencies and genetic heterogeneity. No family had an unusual clustering of cancer. The occurrence of tumours in the blood relatives of CVID patients was not significantly higher than in the relatives of spouse controls. Immunological examination of 30 first degree relatives of the CVID patients revealed three children (2 males and 1 female) with selective IgA deficiency, in one boy combined with elevated serum IgE level. Four relatives with rheumatoid heart disease, 12 cases of gastric or duodenal ulcer, and 14 relatives with thyroid disease represented the most often encountered diagnoses with a possible autoimmune component in their aetiology. PMID:1880404

Vorechovský, I; Litzman, J; Lokaj, J; Sobotková, R

1991-01-01

217

Homeless Families with Children  

Microsoft Academic Search

Previous studies of homelessness have not adequately addressed the relationship between deteriorating living conditions of inner-city neighborhoods and family homelessness. Interviews with 50 families with children who were residents of homeless shelters in two large cities in New York reveal that substandard housing, unscrupulous landlords, and drug-related violence and crime in neighborhoods, as well as nonpayment of rent and domestic

Namkee G. Choi; Lidia J. Snyder

1999-01-01

218

The Dutch founder mutation SDHD.D92Y shows a reduced penetrance for the development of paragangliomas in a large multigenerational family  

PubMed Central

Germline mutations in SDHD predispose to the development of head and neck paragangliomas, and phaeochromocytomas. The risk of developing a tumor depends on the sex of the parent who transmits the mutation: paragangliomas only arise upon paternal transmission. In this study, both the risk of paraganglioma and phaeochromocytoma formation, and the risk of developing associated symptoms were investigated in 243 family members with the SDHD.D92Y founder mutation. By using the Kaplan–Meier method, age-specific penetrance was calculated separately for paraganglioma formation as defined by magnetic resonance imaging (MRI) and for paraganglioma-related signs and symptoms. Evaluating clinical signs and symptoms alone, the penetrance reached a maximum of 57% by the age of 47 years. When MRI detection of occult paragangliomas was included, penetrance was estimated to be 54% by the age of 40 years, 68% by the age of 60 years and 87% by the age of 70 years. Multiple tumors were found in 65% and phaeochromocytomas were diagnosed in 8% of paraganglioma patients. Malignant paraganglioma was diagnosed in one patient (3%). Although the majority of carriers of a paternally inherited SDHD mutation will eventually develop head and neck paragangliomas, we find a lower penetrance than previous estimates from studies based on predominantly index cases. The family-based study described here emphasizes the importance of the identification and inclusion of clinically unaffected mutation carriers in all estimates of penetrance. This finding will allow a more accurate genetic counseling and warrants a ‘wait and scan' policy for asymptomatic paragangliomas, combined with biochemical screening for catecholamine excess in SDHD-linked patients. PMID:19584903

Hensen, Erik F; Jansen, Jeroen C; Siemers, Maaike D; Oosterwijk, Jan C; Vriends, Annette HJT; Corssmit, Eleonora PM; Bayley, Jean-Pierre; van der Mey, Andel GL; Cornelisse, Cees J; Devilee, Peter

2010-01-01

219

Family Privilege  

ERIC Educational Resources Information Center

Family privilege is defined as "strengths and supports gained through primary caring relationships." A generation ago, the typical family included two parents and a bevy of kids living under one roof. Now, every variation of blended caregiving qualifies as family. But over the long arc of human history, a real family was a…

Seita, John R.

2014-01-01

220

Familial Amyloidosis Cutis Dyschromica in Three Siblings: Report from Indonesia  

PubMed Central

Amyloidosis cutis dyschromica (ACD) is an extremely rare type of primary cutaneous amyloidosis. To date there are fewer than 40 published cases worldwide; some were reported affecting several family members. Its resemblance to other common pigmentation disorders makes it rarely recognized at first sight. Our patient, the 12-year-old firstborn son of non-consanguineous parents presented with generalized mottled pigmentation starting from lower extremities. His siblings suffered from similar condition. The clue for diagnosis is the amyloid deposition in the papillary dermis. The etiology of ACD is still unknown, but genetic factors and ultraviolet radiation are implicated. It is proposed that disturbance of keratinocyte repair following ultraviolet radiation results in amyloid deposition. The treatment remains a challenge. Oral acitretin treatment, thought to repair keratinization defect, gave a slight improvement in our case. Our is the first case of ACD reported in Indonesia. PMID:25386328

Hermawan, Melyawati; Rihatmadja, Rahadi; Sirait, Sondang Pandjaitan

2014-01-01

221

Identification of a locus for progressive familial intrahepatic cholestasis PFIC2 on chromosome 2q24.  

PubMed Central

Progressive familial intrahepatic cholestasis (PFIC; OMIM 211600) is the second most common familial cholestatic syndrome presenting in infancy. A locus has previously been mapped to chromosome 18q21-22 in the original Byler pedigree. This chromosomal region also harbors the locus for benign recurrent intrahepatic cholestasis (BRIC) a related phenotype. Linkage analysis in six consanguineous PFIC pedigrees from the Middle East has previously excluded linkage to chromosome 18q21-22, indicating the existence of locus heterogeneity within the PFIC phenotype. By use of homozygosity mapping and a genome scan in these pedigrees, a locus designated "PFIC2" has been mapped to chromosome 2q24. A maximum LOD score of 8.5 was obtained in the interval between marker loci D2S306 and D2S124, with all families linked. Images Figure 1 PMID:9326328

Strautnieks, S S; Kagalwalla, A F; Tanner, M S; Knisely, A S; Bull, L; Freimer, N; Kocoshis, S A; Gardiner, R M; Thompson, R J

1997-01-01

222

RNA Interference Suppression of Genes in Glycosyl Transferase Families 43 and 47 in Wheat Starchy Endosperm Causes Large Decreases in Arabinoxylan Content1[C][W][OPEN  

PubMed Central

The cell walls of wheat (Triticum aestivum) starchy endosperm are dominated by arabinoxylan (AX), accounting for 65% to 70% of the polysaccharide content. Genes within two glycosyl transferase (GT) families, GT43 (IRREGULAR XYLEM9 [IRX9] and IRX14) and GT47 (IRX10), have previously been shown to be involved in the synthesis of the xylan backbone in Arabidopsis, and close homologs of these have been implicated in the synthesis of xylan in other species. Here, homologs of IRX10 TaGT47_2 and IRX9 TaGT43_2, which are highly expressed in wheat starchy endosperm cells, were suppressed by RNA interference (RNAi) constructs driven by a starchy endosperm-specific promoter. The total amount of AX was decreased by 40% to 50% and the degree of arabinosylation was increased by 25% to 30% in transgenic lines carrying either of the transgenes. The cell walls of starchy endosperm in sections of grain from TaGT43_2 and TaGT47_2 RNAi transgenics showed decreased immunolabeling for xylan and arabinoxylan epitopes and approximately 50% decreased cell wall thickness compared with controls. The proportion of AX that was water soluble was not significantly affected, but average AX polymer chain length was decreased in both TaGT43_2 and TaGT47_2 RNAi transgenics. However, the long AX chains seen in controls were absent in TaGT43_2 RNAi transgenics but still present in TaGT47_2 RNAi transgenics. The results support an emerging picture of IRX9-like and IRX10-like proteins acting as key components in the xylan synthesis machinery in both dicots and grasses. Since AX is the main component of dietary fiber in wheat foods, the TaGT43_2 and TaGT47_2 genes are of major importance to human nutrition. PMID:23878080

Lovegrove, Alison; Wilkinson, Mark D.; Freeman, Jackie; Pellny, Till K.; Tosi, Paola; Saulnier, Luc; Shewry, Peter R.; Mitchell, Rowan A.C.

2013-01-01

223

Sugar beet contains a large CONSTANS-LIKE gene family including a CO homologue that is independent of the early-bolting (B) gene locus  

PubMed Central

Floral transition in the obligate long-day (LD) plant sugar beet (Beta vulgaris ssp. vulgaris) is tightly linked to the B gene, a dominant early-bolting quantitative trait locus, the expression of which is positively regulated by LD photoperiod. Thus, photoperiod regulators like CONSTANS (CO) and CONSTANS-LIKE (COL) genes identified in many LD and short-day (SD)-responsive plants have long been considered constituents and/or candidates for the B gene. Until now, the photoperiod response pathway of sugar beet (a Caryophyllid), diverged from the Rosids and Asterids has not been identified. Here, evidence supporting the existence of a COL gene family is provided and the presence of Group I, II, and III COL genes in sugar beet, as characterized by different zinc-finger (B-box) and CCT (CO, CO-like, TOC) domains is demonstrated. BvCOL1 is identified as a close-homologue of Group 1a (AtCO, AtCOL1, AtCOL2) COL genes, hence a good candidate for flowering time control and it is shown that it maps to chromosome II but distant from the B gene locus. The late-flowering phenotype of A. thaliana co-2 mutants was rescued by over-expression of BvCOL1 thereby suggesting functional equivalence with AtCO, and it is shown that BvCOL1 interacts appropriately with the endogenous downstream genes, AtFT and AtSOC1 in the transgenic plants. Curiously, BvCOL1 has a dawn-phased diurnal pattern of transcription, mimicking that of AtCOL1 and AtCOL2 while contrasting with AtCO. Taken together, these data suggest that BvCOL1 plays an important role in the photoperiod response of sugar beet. PMID:18495636

Chia, T. Y. P.; Muller, A.; Jung, C.; Mutasa-Gottgens, E. S.

2008-01-01

224

Reading Comprehension in a Large Cohort of French First Graders from Low Socio-Economic Status Families: A 7-Month Longitudinal Study  

PubMed Central

Background The literature suggests that a complex relationship exists between the three main skills involved in reading comprehension (decoding, listening comprehension and vocabulary) and that this relationship depends on at least three other factors orthographic transparency, children’s grade level and socioeconomic status (SES). This study investigated the relative contribution of the predictors of reading comprehension in a longitudinal design (from beginning to end of the first grade) in 394 French children from low SES families. Methodology/Principal findings Reading comprehension was measured at the end of the first grade using two tasks one with short utterances and one with a medium length narrative text. Accuracy in listening comprehension and vocabulary, and fluency of decoding skills, were measured at the beginning and end of the first grade. Accuracy in decoding skills was measured only at the beginning. Regression analyses showed that listening comprehension and decoding skills (accuracy and fluency) always significantly predicted reading comprehension. The contribution of decoding was greater when reading comprehension was assessed via the task using short utterances. Between the two assessments, the contribution of vocabulary, and of decoding skills especially, increased, while that of listening comprehension remained unchanged. Conclusion/Significance These results challenge the ‘simple view of reading’. They also have educational implications, since they show that it is possible to assess decoding and reading comprehension very early on in an orthography (i.e., French), which is less deep than the English one even in low SES children. These assessments, associated with those of listening comprehension and vocabulary, may allow early identification of children at risk for reading difficulty, and to set up early remedial training, which is the most effective, for them. PMID:24250802

Gentaz, Edouard; Sprenger-Charolles, Liliane; Theurel, Anne; Cole, Pascale

2013-01-01

225

Phase-diagram-guided method for growth of a large crystal of glycoside hydrolase family 45 inverting cellulase suitable for neutron structural analysis  

PubMed Central

Neutron protein crystallography (NPC) is a powerful tool for determining the hydrogen position and water orientation in proteins, but a much larger protein crystal is needed for NPC than for X-ray crystallography, and thus crystal preparation is a bottleneck. To obtain large protein crystals, it is necessary to know the properties of the target protein in the crystallization solution. Here, a crystal preparation method of fungal cellulase PcCel45A is reported, guided by the phase diagram. Nucleation and precipitation conditions were determined by sitting-drop vapor diffusion. Saturation and unsaturation conditions were evaluated by monitoring crystal dissolution, and a crystallization phase diagram was obtained. To obtain a large crystal, crystallization solution was prepared on a sitting bridge (diameter = 5?mm). Initial crystallization conditions were 40?µl of crystallization solution (40?mg?ml?1 protein with 30.5% 3-methyl-1,5-pentanediol in 50?mM tris-HCl pH 8.0) with a 1000?µl reservoir (61% 3-methyl-1,5,-pentanediol in 50?mM tris-HCl pH 8.0) at 293?K. After the first crystal appeared, the concentration of precipitant in the reservoir solution was reduced to 60% to prevent formation of further crystals. Finally, we obtained a crystal of 6?mm3 volume (3?mm × 2?mm × 1?mm), which was suitable for neutron diffraction. PMID:24121328

Nakamura, Akihiko; Ishida, Takuya; Fushinobu, Shinya; Kusaka, Katsuhiro; Tanaka, Ichiro; Inaka, Koji; Higuchi, Yoshiki; Masaki, Mika; Ohta, Kazunori; Kaneko, Satoshi; Niimura, Nobuo; Igarashi, Kiyohiko; Samajima, Masahiro

2013-01-01

226

Cancer, Families, and Family Counselors.  

ERIC Educational Resources Information Center

Examines the role of the family counselor in working with cancer patients and their families. Suggests ways in which the family counselor can work proactively with families in the area of cancer prevention and helping them cope more effectively with its impact on their lives. Uses a clinical case example to illustrate intervention with cancer…

Duffy, Maureen; Gillig, Scott

2003-01-01

227

Gaspra and Ida in families  

NASA Technical Reports Server (NTRS)

The Galileo flyby candidates 951 Gaspra and 243 Ida are both in families. The former is in a complex of families associated with 8 Flora and the latter is in the Koronis family. The Flora and the Koronis families are described. The Galileo spacecraft will have the opportunity to sample fragments from two types of impacts; one impact totally destroyed the parent body and the other left a large body behind. The types of Ss are also different, the colors of Gaspra and the other Ss in the complex of families near 8 Flora are much redder in U-V than Ida and the Ss of the Koronis family.

Williams, James G.

1992-01-01

228

Evolution of the Discs large gene family provides new insights into the establishment of apical epithelial polarity and the etiology of mental retardation.  

PubMed

Cell polarity is essential to the function of many cell types, such as epithelial cells and neurons. The Discs large (Dlg) scaffolding protein was identified in Drosophila as a major regulator of basolateral epithelial identity. Four Dlg orthologs (Dlg1 through 4) are found in vertebrates, and mutations in the human Dlg3 gene are associated with X-linked mental retardation. We recently found that Dlg3 controls apical epithelial polarity and tight junction formation and contributes to neural induction in mouse development.(1) During evolution, Dlg3 acquired specific PPxY motifs, which bind to the WW domains of the E3 ubiquitin ligases, Nedd4 and Nedd4-2. This interaction results in monoubiquitination of Dlg3, leading to directed microtubule-dependent protein trafficking, via the exocyst complex, in different polarized cell types. Directed trafficking of Dlg3 plays an important role, during both mammalian development and in adulthood, in the establishment and maintenance of specialized apical cell junctions, such as tight junctions in epithelial cells and synapses in neurons. PMID:22896795

Lickert, Heiko; Van Campenhout, Claude A

2012-05-01

229

Family Life  

MedlinePLUS

... that different families have different communication and coping styles. Consider how your family reacts in a crisis ... Learn more about how to get support for parenting while living with cancer . The importance of communication ...

230

Family History  

MedlinePLUS

... Home CDC 24/7: Saving Lives. Protecting People.™ Genomics All CDC Topics Search The CDC Note: Javascript ... visit this page: About CDC.gov . Public Health Genomics Genomics Family Health History Share Compartir Family History ...

231

Family History  

MedlinePLUS

... Complications Post Treatment and Outcome GTranslate Understanding : Family History Familial intracranial aneurysms are generally defined as the ... patients with an Intracranial Aneurysm (IA) have a history of smoking at some time in their life. ...

232

Family Involvement.  

ERIC Educational Resources Information Center

Family involvement in schools will work only when perceived as an enlarged concept focusing on all children, including those from at-risk families. Each publication reviewed here is specifically concerned with family involvement strategies concerned with all children or targeted at primarily high risk students. Susan McAllister Swap looks at three…

Liontos, Lynn Balster

1992-01-01

233

The mouse DNA binding protein Rc for the kappa B motif of transcription and for the V(D)J recombination signal sequences contains composite DNA-protein interaction domains and belongs to a new family of large transcriptional proteins  

SciTech Connect

Rc is a DNA binding protein with dual specificities for the V(D)J recombination signal sequences and for the B motif of the immunoglobulin kappa chain gene enhancer. The largest Rc transcript present in lymphoid cells/tissues is {approximately} 9 kb. Molecular cloning and sequence determination for 8822 bp of mouse Rc cDNA revealed an open reading frame of 2282 amino acids and long 5{prime}- and 3{prime}- untranslated regions. The derived amino acid sequence contains multiple DNA and protein interaction domains. Composite ZAS structures with tandem zinc fingers, and acidic motif, and a Ser/Thr-rich segment are located near the N-terminal and the C-terminal regions. The middle region of Rc contains a lone zinc finger, an acidic motif, a Ser-rich region, a nucleus localization signal, and GTPase motifs. Cloning and characterization of a mouse Rc gene show that the Rc cDNA corresponds to seven exons located in a genomic region spanning 70 kb. Exon 2 is exceptionally large, with 5487 bp. cDNA cloning and Northern blot analyses revealed multiple Rc transcripts, probably generated by alternative splicings. Sequence comparisons show that Rc belongs to a ZAS protein family that is involved in gene transcription and/or DNA recombination. The major histocompatibility complex class I gene enhancer binding proteins MBP1 and MBP2 are other representatives of this ZAS protein family. 43 refs., 6 figs., 2 tabs.

Wu, Lai-Chu; Liu, Yiling; Li, Zhiling [Ohio State Univ., Columbus, OH (United States)] [and others] [Ohio State Univ., Columbus, OH (United States); and others

1996-08-01

234

Italian families and family interventions.  

PubMed

In Italy, as in many countries, relatives are closely involved in caring for persons with physical and mental disorders. The Italian scenario lends itself to routine involvement of family members in psychiatric treatment because, despite becoming smaller and smaller, Italian families keep close ties, and men and women do not leave the parental home until relatively late. The authors describe the impact of international family psychosocial research on the Italian mental health services (MHSs) and the main psychosocial interventions currently in use, including family psychoeducational interventions and the "Milan family therapy approach." They also highlight the contribution Italian researchers have given to the study of important variables in integrated mental disorder care, such as family burden of care, relatives' attitudes, family functioning, and satisfaction with the MHSs. Finally, they discuss the difficulties of implementing and disseminating family interventions within the Italian MHS, despite the growing evidence of their effectiveness. PMID:24879572

Casacchia, Massimo; Roncone, Rita

2014-06-01

235

Family issues in child anxiety: Attachment, family functioning, parental rearing and beliefs  

Microsoft Academic Search

Family studies have found a large overlap between anxiety disorders in family members. In addition to genetic heritability, a range of family factors may also be involved in the intergenerational transmission of anxiety. Evidence for a relationship between family factors and childhood as well as parental anxiety is reviewed. Four groups of family variables are considered: (I) attachment; (II), aspects

Susan M. Bögels; Margaret L. Brechman-Toussaint

2006-01-01

236

A new family programme in Zhejiang province.  

PubMed

Zhejiang Province in China has promoted a new family planning program since April 1993. The program stresses delayed marriage and childbearing, fewer and healthier births, modernization of family life, and prosperity through hard work. The people are receptive to the new program out of a desire for an improved standard of living. The objective is to build small, modern families who 1) practice deferred marriage and childbearing; 2) voluntarily practice family planning and have no unplanned births; 3) practice avoidance of consanguineous marriage, become sterilized if a carrier of a hereditary disease of chromosomal abnormality, and use premarital education and counseling and proper prenatal care; 4) uphold the laws and maintain discipline in action to avoid criminal behavior; 5) establish families that respect the old, care for children, and help their neighbors; 6) complete 9 years of compulsory education; and 7) create well being through hard work. The program is compatible with the strategy of the "three stresses" and an integrated approach. IEC and service provision are important components in program implementation. The target population are the masses and grassroots cadres, particularly those in the childbearing ages. IEC will be directed in different ways to different groups. Those aged 18-35 years will receive education. Face to face interaction with family planning workers and lectures will be directed to grassroots cadres. The mass media will be employed to reach the masses. The messages will include information and persuasion to adopt new families, accept family planning regulations, and learn about contraceptive use, healthy births and childrearing, education, health care, sex education, and income generation skills. Classes will be conducted for groups, such as teenagers, unmarried youth, pregnant women, and lactating women. Priority will be given to couples that accept the certificates for one child; favoritism will be granted for allocation of housing; acceptance in kindergartens and schools, employment, and military positions; and receipt of business licenses and poverty aide. Sterilization will be rewarded with longer paid leave and subsidies. Services will include contraceptive provision and follow-up, infertility treatment, gynecological check-ups, sex education, old age pensions, premarital counseling, and other quality services. PMID:12346835

Xu, B

1994-04-01

237

What makes a family reliable?  

NASA Technical Reports Server (NTRS)

Asteroid families are clusters of asteroids in proper element space which are thought to be fragments from former collisions. Studies of families promise to improve understanding of large collision events and a large event can open up the interior of a former parent body to view. While a variety of searches for families have found the same heavily populated families, and some searches have found the same families of lower population, there is much apparent disagreement between proposed families of lower population of different investigations. Indicators of reliability, factors compromising reliability, an illustration of the influence of different data samples, and a discussion of how several investigations perceived families in the same region of proper element space are given.

Williams, James G.

1992-01-01

238

Genome scan of schizophrenia families in a large Veterans Affairs Cooperative Study sample: evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14.  

PubMed

Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes but, given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. We report results from a genome scan of 166 schizophrenia families collected through the Department of Veterans Affairs Cooperative Studies Program. Our definition of affection status included schizophrenia and schizoaffective disorder, depressed type and we defined families as European American (EA) and African American (AA) based on the probands' and parents' races based on data collected by interviewing the probands. We also assessed evidence for racial heterogeneity in the regions most suggestive of linkage. The maximum LOD score across the genome was 2.96 for chromosome 18, at 0.5 cM in the combined race sample. Both racial groups showed LOD scores greater than 1.0 for chromosome 18. The empirical P-value associated with that LOD score is 0.04 assuming a single genome scan for the combined sample with race narrowly defined, and 0.06 for the combined sample allowing for broad and narrow definitions of race. The empirical P-value of observing a LOD score as large as 2.96 in the combined sample, and of at least 1.0 in each racial group, allowing for narrow and broad racial definitions, is 0.04. Evidence for the second and third largest linkage signals come solely from the AA sample on chromosomes 6 (LOD = 2.11 at 33.2 cM) and 14 (LOD = 2.13 at 51.0). The linkage evidence differed between the AA and EA samples (chromosome 6 P-value = 0.007 and chromosome 14 P-value = 0.004). PMID:16152571

Faraone, S V; Skol, A D; Tsuang, D W; Young, K A; Haverstock, S L; Prabhudesai, S; Mena, F; Menon, A S; Leong, L; Sautter, F; Baldwin, C; Bingham, S; Weiss, D; Collins, J; Keith, T; Vanden Eng, J L; Boehnke, M; Tsuang, M T; Schellenberg, G D

2005-11-01

239

Family planning and vocations.  

PubMed

In many Western countries the number of vocations has fallen to as low as 1/10 what it was a generation ago. The author blames several factors for this occurrence. An identity crisis among the members of the faith that is a result of broken homes is seen as a factor. The growth of materialism and the consumer mentality is seen as another factor leading people away from the life of sacrifices for God. But the author feels that the strongest force behind this fact is the use of family planning without a serious reason. Catholics are only allowed to use family planning if they have a serious health or financial reason for doing so, and then it can only be a natural method. Large families reinforce the ideals and attitudes necessary to create a person that is willing to seek a vocation. People from broken homes are not usually accepted because the matter of perseverance becomes a problem. When a child grows up in a large family it learns to make sacrifices. It also sees its parents making sacrifices for the children. It is the author's opinion what without this atmosphere of sacrifice at home, one is not prepared for the sacrifices that go with a vocation. It is also the author's opinion that families in the 3rd World tend to be larger, poorer yet still happier then Western families. Further, vocations in the 3rd World are abundant. PMID:12179689

Burke, C

1989-01-01

240

A combination of mutations in AKR1D1 and SKIV2L in a family with severe infantile liver disease  

E-print Network

with neonatal hepatitis -consanguineous family with severe infantile liver disease. The nt 2 and affected sibling (V:8; P3). Solid symbols represent affected pper mutation is a homozygous single base G deletion in AKR1D1 sX11) and lower mutation a single base C... features suggestive of microvillous inclusion disease, tufting enteropathy or autoimmune enteropathy. The serum immunoglobulin levels were low (IgG < 0.01 g/L (0.3-0.5). Investigation of the patient’s hair identified trichorrhexis nodosa with low cysteine...

Morgan, Neil V; Hartley, Jane L; Setchell, Kenneth DR; Simpson, Michael A; Brown, Rachel; Tee, Louise; Kirkham, Sian; Pasha, Shanaz; Trembath, Richard C; Maher, Eamonn R; Gissen, Paul; Kelly, Deirdre A

2013-05-16

241

Family Issues  

MedlinePLUS

... their marriage, other children, work, finances, and personal relationships and responsibilities. Parents now have to shift much of their resources ... needs of a child with ASD complicates familial relationships, especially with siblings. However, parents can help their family by informing their other ...

242

Family Life.  

ERIC Educational Resources Information Center

Focuses on various aspects of mammal family life ranging from ways different species are born to how different mammals are raised. Learning activities include making butter from cream, creating birth announcements for mammals, and playing a password game on family life. (ML)

Naturescope, 1986

1986-01-01

243

Genetic analysis of BRCA1 and BRCA2 in breast/ovarian cancer families from Aragon (Spain): two novel truncating mutations and a large genomic deletion in BRCA1.  

PubMed

We screened BRCA1 and BRCA2 germline mutations in 60 high-risk breast and/or ovarian cancer patients and 20 relatives from Aragon (Spain) by DHPLC (Denaturing High Performance Liquid Chromatography) and direct sequencing of the entire coding sequence and the splicing sites of both genes. We have identified 17 different pathogenic mutations: 8 in BRCA1 and 9 in BRCA2 in 60 unrelated patients and 50% of relatives were carriers. The prevalence of pathogenic mutations in this study was 33.33%. Two truncating mutations are novel: c.5024_5025delGA in exon 16 of BRCA1 and c.2929delC in exon 11 of BRCA2 (numbered after GenBank U14680 and U43746). Multiplex Ligation Dependent Probe Amplification (MLPA) was performed for large mutational scanning of both genes and a large genomic deletion in BRCA1 was found (DelEx8-13). Furthermore, five mutations are described for the first time in Spanish population: c.1191delC, c.3478_3479delTT and c.6633_6637delCTTAA (BRCA1) and c.3972_3975delTGAG and 3908_3909delTG (BRCA2). Three mutations have been reported previously once in Spain: c.3600_3610del11 (BRCA1), c.5804_5807delTTAA (BRCA2) and c.9246C>A (BRCA2). The mutation c.5374_5377delTATG has been found before only in two unrelated families from Castilla-Leon, Spain (BRCA2). Frequent mutations described in Spanish population have also been present: c.187_188delAG, c.5242C>A and c.5385insC in BRCA1 and c.3492_3493insT and c.9254_9258delATCAT in BRCA2. c.5242C>A, 3972_3975delTGAG and c.5804_5807delTTAA were the recurrent mutations found. Fifteen different unclassified variants were identified (25% families). Although specific BRCA1 and BRCA2 mutations are recurrently reported as a result of genetic founder effects we conclude that heterogeneous ethnicity increases the variety of mutations that can be found in Spanish populations. PMID:18176857

Miramar, M D; Calvo, M T; Rodriguez, A; Antón, A; Lorente, F; Barrio, E; Herrero, A; Burriel, J; García de Jalón, A

2008-11-01

244

Familial Chronic Lymphocytic Leukemia  

PubMed Central

Purpose of Review Families with multiple individuals affected with chronic lymphocytic leukemia (CLL) and other related B-cell tumors have been described in the literature and strong familial aggregation has been seen in population studies. However, predisposing germ line mutations have not been identified. We will discuss the spectrum of conditions associated with CLL in families and the advances in identifying the underlying susceptibility genes. Recent Findings Familial CLL does not appear to differ substantially from sporadic CLL in terms of prognostic markers and clinical outcome, although it may be associated with more indolent disease. The precursor condition, monoclonal B-cell lymphocytosis (MBL) also aggregates in CLL families. Linkage studies have been conducted in high-risk CLL families to screen the whole genome for susceptibility loci but no gene mutations have yet been identified by this method. Association studies of candidate genes have implicated several genes as being important in CLL but more studies are needed. Results from whole genome association studies are promising. Summary The ability to conduct large scale genomic studies in unrelated CLL cases and in high risk CLL families will play an important role in detecting susceptibility genes for CLL over the next few years and thereby help to delineate etiologic pathways. PMID:20389242

Goldin, Lynn R.; Slager, Susan L.; Caporaso, Neil E.

2010-01-01

245

Family Theory and Family Health Research  

PubMed Central

Different family theories can be applied to different aspects of how families experience health and illness. The family health and illness cycle describes the phases of a family's experience, beginning with health promotion and risk reduction, then family vulnerability and disease onset or relapse, family illness appraisal, family acute response, and finally family adaptation to illness and recovery. For each phase, specific family theories that are most appropriate for guiding family and health research are discussed. PMID:21229056

Doherty, William J.

1991-01-01

246

Genetic analysis of primary microcephaly in Indian families: novel ASPM mutations.  

PubMed

Patients with primary microcephaly, an autosomal recessive trait, have mild to severe mental retardation without any other neurological deficits. It is a genetically heterogeneous disorder with six known loci: MCPH1 to MCPH6. Only the genes for MCPH1 and MCPH5 have been identified so far. We have ascertained nine consanguineous families with primary microcephaly from India. To establish linkage of these nine families to known MCPH loci, microsatellite markers were selected from the candidate regions of each of the six known MCPH loci and used to genotype the families. The results were suggestive of linkage of three families to the MCPH5 locus and one family to the MCPH2 locus. The remaining five families were not linked to any of the known loci. DNA-sequence analysis identified one known (Arg117X) and two novel (Trp1326X and Gln3060X) mutations in the three MCPH5-linked families in a homozygous state. Three novel normal population variants (i.e., c.7605G > A, c.4449G > A, and c.5961 A > G) were also detected in the ASPM gene. PMID:15355437

Kumar, A; Blanton, S H; Babu, M; Markandaya, M; Girimaji, S C

2004-10-01

247

Large vestibular aqueduct syndrome.  

PubMed

Large Vestibular Aqueduct Syndrome is a congenital malformation of the temporal bone characterised by early onset of sensorineural hearing loss and vestibular disturbance. Familial large vestibular aqueduct syndrome suggests autosomal recessive or X-linked inheritance and accounts for non-syndromic sensorineural hearing loss in these patients. PMID:16570713

Dipak, S; Prepageran, N; Sazila, A S; Rahmat, O; Raman, R

2005-10-01

248

A Family of Adders  

Microsoft Academic Search

Binary carry-propagating addition can be efficiently expressed as a prefix computation. Several examples of adders based on such a formulation have been published and efficient implementations are numerous. Chief among the known constructions are those of Kogge and Stone (1973) and Ladner and Fischer (1980). In this work we show that these are end cases of a large family of

Simon Knowles

2001-01-01

249

Genetics Home Reference: Familial cylindromatosis  

MedlinePLUS

... sweat glands. People with familial cylindromatosis typically develop large numbers of tumors called cylindromas. While previously thought to ... and neck. They grow larger and increase in number over time. In severely ... into a large, turban-like growth. Large growths frequently develop open ...

250

Family Meals  

MedlinePLUS

... less likely to smoke, drink alcohol, or use marijuana and other drugs, and are more likely to have healthier diets as adults, studies have shown. Beyond health and nutrition, family meals provide a valuable opportunity ...

251

Usefulness of cardiovascular family history data for population-based preventive medicine and medical research (The Health Family Tree Study and the NHLBI Family Heart Study)  

Microsoft Academic Search

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family

Roger R Williams; Steven C Hunt; Gerardo Heiss; Michael A Province; Jeannette T Bensen; Millicent Higgins; Robert M Chamberlain; Joan Ware; Paul N Hopkins

2001-01-01

252

Fact Families  

NSDL National Science Digital Library

In this lesson, the relationship of addition to subtraction is explored with books and with connecting cubes. Students search for related addition and subtraction facts for a given number using a virtual or actual calculator to find differences. They also investigate fact families when one addend is 0 as well as when the addends are the same. Students will: find missing addends, review the additive identity, generate fact families given two addends or given one addend and the sum.

Illuminations

2012-03-31

253

Spectrum of Perforin Gene Mutations in Familial Hemophagocytic Lymphohistiocytosis  

PubMed Central

Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disease of early childhood characterized by nonmalignant accumulation and multivisceral infiltration of activated T lymphocytes and histiocytes (macrophages). Cytotoxic T and natural killer (NK) cell activity is markedly reduced or absent in these patients, and mutations in a lytic granule constituent, perforin, were recently identified in a number of FHL individuals. Here, we report a comprehensive survey of 34 additional patients with FHL for mutations in the coding region of the perforin gene and the relative frequency of perforin mutations in FHL. Perforin mutations were identified in 7 of the 34 families investigated. Six children were homozygous for the mutations, and one patient was a compound heterozygote. Four novel mutations were detected: one nonsense, two missense, and one deletion of one amino acid. In four families, a previously reported mutation at codon 374, causing a premature stop codon, was identified, and, therefore, this is the most common perforin mutation identified so far in FHL patients. We found perforin mutations in 20% of all FHL patients investigated (7/34), with a somewhat higher prevalence, ?30% (6/20), in children whose parents originated from Turkey. No other correlation between the type of mutation and the phenotype of the patients was evident from the present study. Our combined results from mutational analysis of 34 families and linkage analysis of a subset of consanguineous families indicate that perforin mutations account for 20%–40% of the FHL cases and the FHL 1 locus on chromosome 9 for ?10%, whereas the major part of the FHL cases are caused by mutations in not-yet-identified genes. PMID:11179007

Göransdotter Ericson, Kim; Fadeel, Bengt; Nilsson-Ardnor, Sofie; Söderhäll, Cilla; Samuelsson, AnnaCarin; Janka, Gritta; Schneider, Marion; Gürgey, Aytemiz; Yalman, Nevin; Révész, Tom; Egeler, R. Maarten; Jahnukainen, Kirsi; Storm-Mathiesen, Ingebjörg; Haraldsson, Ásgeir; Poole, Janet; de Saint Basile, Geneviève; Nordenskjöld, Magnus; Henter, Jan-Inge

2001-01-01

254

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

PubMed

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

Sher, Gulab; Naeem, Muhammad

2014-01-01

255

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

PubMed Central

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

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

2011-01-01

256

Family Hypnotherapy.  

ERIC Educational Resources Information Center

A therapeutic model to help families activate experiential and right hemispheric functioning through hypnosis is presented in detail, together with a clinical illustration. Different situations in which this model is effective are mentioned and one such set of circumstances is described. (Author)

Araoz, Daniel L.; Negley-Parker, Esther

1985-01-01

257

Family planning concept.  

PubMed

Family planning is defined as the voluntary, responsible decision made by individuals and couples as to the desired family size and timing of births. Therefore on the microlevel it means children are born because they are wanted and provided for and on the macrolevel it contributes to the betterment of human life. This paper deals with the health consequences of uncontrolled fertility. Health risks are related to birth order, social class, maternal age, birth intervals, and family size are described, including: 1) fetal, infant, and childhood morbidity and mortality, 2) poor physical and intellectual development of the unwanted child, 3) pregnancy wastage, 4) maternal risk of illness and death, 5) father's risk of hypertension and gastric ulcers, 6) marital risk, 7) poor nutrition, 8) environmental hazards such as overcrowding, poor water supply, atmospheric contamination, 9) increased incidence of genetic diseases, and 10) mental health problems of parents as well as children due to strains caused by large families. Even though the responsibility of family planning lies mainly with married couples it is the duty of health workers to inform the people of the problems that arise in a situation of uncontrolled reproduction. PMID:6920653

Dumindin, J B

1981-01-01

258

Homolog of the polymorphic 4q35 FSHD locus (p13E-11; D4F104S1) maps to 10qter; exclusion as a second FSHD locus in a large Danish family  

SciTech Connect

Facioscapulohumeral muscular dystrophy (FSHD) has been mapped to 4q35 and shown to be associated with deletions that are detectable using probe p13E-11 (D4104S1). These deletions reside within highly polymorphic restriction fragments (20-300 kb) which can normally only be resolved completely using pulsed-field gel electrophoresis (PFGE). Family studies showed that p13E-11 detects two non-allelic loci, only one of which originates from 4q35 origin. In 20 CEPH families, 8 individuals were identified showing a `small` EcoRI fragment detectable by conventional Southern blotting. Linkage analysis allowed assignment of these fragments to 10qter (D10S212 and D10S180) in all families tested. Since FSHD shows genetic heterogeneity, this second p13E-11 locus on 10qter became an interesting candidate as a second FSHD family did not provide evidence for linkage on chromosome 10qter.

Frants, R.R.; Bakker, E.; Vossen, R.H.A.M. [and others

1994-09-01

259

The Family Child Care Licensing Study, 1999.  

ERIC Educational Resources Information Center

This report presents the findings of the 1999 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1998 study. Data on small family child care homes and group or large family child care homes are organized in 22 categories: (1) number of regulated homes; (2)…

Children's Foundation, Washington, DC.

260

Family Child Care Licensing Study, 2000.  

ERIC Educational Resources Information Center

This report presents the findings of the 2000 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 1999 study. Data on small family child care homes and group or large family child care homes are organized in 23 categories: (1) number of regulated homes; (2)…

Kelly, Nia, Comp.

261

Family Child Care Licensing Study, 2001.  

ERIC Educational Resources Information Center

This report presents the findings of the 2001 national survey of state child care regulatory agencies to update and expand family child care regulatory information published in the 2000 study. Data on small family child care homes and group or large family child care homes are organized into the following 23 categories: (1) number of regulated…

Children's Foundation, Washington, DC.

262

The case of the missing Ceres family  

NASA Astrophysics Data System (ADS)

Ceres is unusual among large (>250 km) asteroids in lacking a dynamical family. We explore possible explanations, noting that its particularly large size and the ubiquity of families associated with other large asteroids makes avoidance of a sufficiently-sized collision by chance exceedingly unlikely. Current models of Ceres' thermal history and interior structure favor a differentiated object with an icy near-surface covered by an ?0.1-1 km lag deposit, which could result in a collisional family of diverse, predominately icy bodies. We predict that sublimation of an icy Ceres family would occur on timescales of hundreds of millions of years, much shorter than the history of the Solar System. Sublimation on a Ceres family body would be aided by a low non-ice fraction and a high average temperature, both of which would inhibit lag deposit development. Because there seems to be no likely mechanism for removing a rocky Ceres family, and because the formation of a Ceres family of some kind seems nearly statistically inevitable, the lack of a Ceres family is indirect but independent evidence for Ceres' differentiation. All of the other large asteroids lacking dynamical families (704 Interamnia, 52 Europa, and 65 Cybele) have spectral properties similar to Ceres, or otherwise suggesting ice at their surfaces. While other large asteroids with similar spectral properties do have families (24 Themis, 10 Hygiea, 31 Euphrosyne), their families are not well understood, particularly Hygiea.

Rivkin, Andrew S.; Asphaug, Erik; Bottke, William F.

2014-11-01

263

Family Structure and Family Processes in Mexican American Families  

PubMed Central

Despite increases in single-parent families among Mexican Americans (MA), few studies have examined the association of family structure and family adjustment. Utilizing a diverse sample of 738 Mexican American families (21.7% single parent), the current study examined differences across family structure on early adolescent outcomes, family functioning, and parent-child relationship variables. Results revealed that early adolescents in single parent families reported greater school misconduct, CD/ODD and MDD symptoms, and greater parent-child conflict than their counterparts in two parent families. Single parent mothers reported greater economic hardship, depression and family stress. Family stress and parent-child conflict emerged as significant mediators of the association between family structure and early adolescent outcomes, suggesting important processes linking MA single parent families and adolescent adjustment. PMID:21361925

Zeiders, Katharine H.; Roosa, Mark W.; Tein, Jenn-Yun

2010-01-01

264

Birth order, family size, and achievement: family structure and wage determination.  

PubMed

The influence of birth order and childhood family size on future achievement is discussed. Two major empirical findings are presented by the author. "First, neither birth order nor childhood family size significantly influences the level or growth rate of wages, a result that is consistent with previous research. Second, family size is both a statistically and economically significant determinant of women's employment status: women from small families work less than women from large families when they are young and more than women from large families when they are more mature." The geographical focus is on the United States. PMID:12317089

Kessler, D

1991-10-01

265

Genetic analysis of Chinese families reveals a novel truncation allele of the retinitis pigmentosa GTPase regulator gene  

PubMed Central

AIM To make comprehensive molecular diagnosis for retinitis pigmentosa (RP) patients in a consanguineous Han Chinese family using next generation sequencing based Capture-NGS screen technology. METHODS A five-generation Han Chinese family diagnosed as non-syndromic X-linked recessive RP (XLRP) was recruited, including four affected males, four obligate female carriers and eleven unaffected family members. Capture-NGS was performed using a custom designed capture panel covers 163 known retinal disease genes including 47 RP genes, followed by the validation of detected mutation using Sanger sequencing in all recruited family members. RESULTS Capture-NGS in one affected 47-year-old male reveals a novel mutation, c.2417_2418insG:p.E806fs, in exon ORF15 of RP GTPase regulator (RPGR) gene results in a frameshift change that results in a premature stop codon and a truncated protein product. The mutation was further validated in three of four affected males and two of four female carriers but not in the other unaffected family members. CONCLUSION We have identified a novel mutation, c.2417_2418insG:p.E806fs, in a Han Chinese family with XLRP. Our findings expand the mutation spectrum of RPGR and the phenotypic spectrum of XLRP in Han Chinese families, and confirms Capture-NGS could be an effective and economic approach for the comprehensive molecular diagnosis of RP.

Hu, Fang; Zeng, Xiang-Yun; Liu, Lin-Lin; Luo, Yao-Ling; Jiang, Yi-Ping; Wang, Hui; Xie, Jing; Hu, Cheng-Quan; Gan, Lin; Huang, Liang

2014-01-01

266

A novel autosomal recessive non-syndromic deafness locus (DFNB35) maps to 14q24.1–14q24.3 in large consanguineous kindred from Pakistan  

Microsoft Academic Search

Autosomal recessive nonsyndromic deafness is one of the most frequent forms of inherited hearing impairment. Over 30 autosomal recessive nonsyndromic hearing loss loci have been mapped, and 15 genes have been isolated. Of the over 30 reported autosomal recessive nonsyndromic hearing loss (NSHL) loci, the typical phenotype is prelingual non-progressive severe to profound hearing loss with the exception of DFNB8,

Muhammad Ansar; Mohammad Amin ud Din; Muhammad Arshad; Muhammad Sohail; Mohammad Faiyaz-Ul-Haque; Sayedul Haque; Wasim Ahmad; Suzanne M Leal

2003-01-01

267

Familiality of female and male homosexuality  

Microsoft Academic Search

We examined data from a large cohort of homosexual and heterosexual females and males concerning their siblings' sexual orientations. As in previous studies, both male and female homosexuality were familial. Homosexual females had an excess of homosexual brothers compared to heteroxual subjects, thus providing evidence that similar familial factors influence both male and female homosexuality. Furthermore, despite the large sample

J. Michael Bailey; Alan P. Bell

1993-01-01

268

Familial pineocytoma.  

PubMed

We present the first report on familial pineocytoma. The propositus, a 31-year-old man, presented with incontinence due to a cystic and haemorrhagic tumour of the pineal region. His 34-year-old sister, who had suffered from tinnitus for several years, also had a pineal tumour. Histopathology following tumour resection revealed pineocytomas (WHO grade 1). Cerebral MRI examinations of the patient's brother and father did not reveal any pineal region abnormalities. Their mother had developed breast cancer at the age of 43. Although not impossible, it is rather unlikely that pineocytomas occurring in siblings are pure coincidence because of the rarity of this type of tumour. PMID:22699425

Gempt, Jens; Ringel, Florian; Oexle, Konrad; Delbridge, Claire; Förschler, Annette; Schlegel, Jürgen; Meyer, Bernhard; Schmidt-Graf, Friederike

2012-08-01

269

Co-occurrence of Distinct Ciliopathy Diseases in Single Families Suggests Genetic Modifiers  

PubMed Central

Disorders within the “ciliopathy” spectrum include Joubert (JS), Bardet–Biedl syndromes (BBS), and nephronophthisis (NPHP). Although mutations in single ciliopathy genes can lead to these different syndromes between families, there have been no reports of phenotypic discordance within a single family. We report on two consanguineous families with discordant ciliopathies in sibling. In Ciliopathy-672, the older child displayed dialysis-dependent NPHP whereas the younger displayed the pathognomonic molar tooth MRI sign (MTS) of JS. A second branch displayed two additional children with NPHP. In Ciliopathy-1491, the oldest child displayed classical features of BBS whereas the two younger children displayed the MTS. Importantly, the children with BBS and NPHP lacked MTS, whereas children with JS lacked obesity or NPHP, and the child with BBS lacked MTS and NPHP. Features common to all three disorders included intellectual disability, postaxial polydactyly, and visual reduction. The variable phenotypic expressivity in this family suggests that genetic modifiers may determine specific clinical features within the ciliopathy spectrum. © 2011 Wiley Periodicals, Inc. PMID:22002901

Zaki, Maha S; Sattar, Shifteh; Massoudi, Rustin A; Gleeson, Joseph G

2011-01-01

270

Distribution of Mycorrhizal Types among Alpine Vascular Plant Families on the Beartooth Plateau, Rocky Mountains, U.S.A., in Reference to Large-Scale Patterns in Arctic–Alpine Habitats  

Microsoft Academic Search

Mycorrhizal symbiosis is critical to plant establishment and survival, influences plant community structure and function, and could be particularly important in harsh environments such as the alpine tundra. An examination of 53 vascular plant species in 21 families from alpine areas of the Beartooth Plateau (Rocky Mountains) revealed most were mycorrhizal (68%) and four distinct types of symbioses were present.

Cathy L. Cripps; Leslie H. Eddington

2005-01-01

271

DEPLOYMENT & THE MILITARY FAMILY  

E-print Network

1 DEPLOYMENT & THE MILITARY FAMILY NEW ORLEANS, LOUISIANA ACTIVE DUTY MILITARY FAMILY MEMBERS).............................................................................................. 3 III. HEALTH & MENTAL HEALTH RESOURCES FOR IMMEDIATE FAMILY MEMBERS OF ACTIVE DUTY MILITARY RESOURCES, INFORMATION & REFERRAL SOURCES FOR IMMEDIATE FAMILY MEMBERS OF ACTIVE DUTY MILITARY PERSONNEL

272

Military Families Considering Adoption  

MedlinePLUS

... Military Families Considering Adoption: A Factsheet for Families Military Families Considering Adoption Email Order (Free) Print (PDF ... Published: 2010 Adoption is a realistic option for military personnel who want to expand their families, and ...

273

Family-centered rounds.  

PubMed

Family-centered rounds (FCRs) are multidisciplinary rounds that involve medical teams partnering with patients and families in daily medical decision-making. Multiple FCR benefits have been identified including improving patient satisfaction, communication, discharge planning, medical education, and patient safety. Main barriers to FCRs are variability in attending rounding, duration of rounds, physical constrains of large teams and small rooms, specific and sensitive patient conditions, and lack of training of residents, students, and faculty on how to conduct effective and effecient FCRs. In the last decade, many programs have incorporated FCRs into daily practice due to their multiple perceived benefits. Future FCRs should focus on better operationalizing of FCRs and reporting on objective outcomes measures such as improved communication, coordination, and patient satisfaction that are crucial for healthcare. PMID:25084715

Mittal, Vineeta

2014-08-01

274

Familial FSGS.  

PubMed

Focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome can be caused by rare highly penetrant mutations in number of genes. FSGS can follow both recessive and dominant inheritance patterns. In general, recessive forms present early, whereas the autosomal dominant forms present in adolescence or adulthood. Many of the genes found to be mutated in FSGS and nephrotic syndrome patients encode proteins essential for normal podocyte structure and/or function. An exception appears to be APOL1, which harbors common variants responsible for the high rate of FSGS and other nephropathies in people of recent African ancestry. Familial FSGS should be regarded as part of a spectrum of inherited glomerulopathies where the precise histologic presentation may depend on the age of onset, function of the responsible gene and gene products, and other factors. PMID:25168831

Pollak, Martin R

2014-09-01

275

Positive Family Functioning.  

ERIC Educational Resources Information Center

The persistence of the nuclear family as the primary social unit in the United States and most all other societies, especially complex ones, is a fact. Values shape the definition of family, especially the "good family," and the "great debate" of this period on family failure, family corruption and the family's near demise originates in…

Sussman, Marvin B.

276

Reclaiming Family Privilege  

ERIC Educational Resources Information Center

The pull for family is strong, almost primeval, most likely it is evolutionary, and for those lacking the benefit of family or Family Privilege, the loss of family is painful and profoundly sad. Young people who struggle to cope without stable family connections are profoundly aware of their lack of "Family Privilege." In this article, the author…

Seita, John

2012-01-01

277

Final Evaluation Report: Family to Family Program.  

ERIC Educational Resources Information Center

This evaluation report of the Family to Family Program assesses parental attitudes towards their Family to Family experience and the functioning of their emotionally impaired children. It reviews issues of goal achievement; the impact on the targeted problem; service population demographics; and sustainability. Related topics include…

Ramey, Luellen; Meyer, David P.

278

Thankful for Family and Foods! (An ABLE Teaching Unit).  

ERIC Educational Resources Information Center

The teaching unit focuses on a month (November) of primary grade learning activities which focus on being thankful for food, family, and friends. Concepts stressed throughout the unit include: We are all part of the large family of Americans; Families are made up of a variety of people and our families are usually different from each other;…

Barringer, Mary Dean; And Others

279

Familial Hypercholesterolaemia  

PubMed Central

Familial hypercholesterolaemia (FH), defined as the heritable occurrence of severe hypercholesterolaemia with cholesterol deposits in tendons and premature heart disease, is caused by at least four genes in sterol and lipoprotein pathways and displays varying gene-dose effects. The genes are the low-density lipoprotein (LDL) receptor, apolipoprotein (apo) B, proprotein convertase subtilisin/kexin 9, and the autosomal recessive hypercholesterolaemia (ARH) adaptor protein. All of these disorders have in common defective clearance of LDL within a complex system of lipid and lipoprotein metabolism and regulation. Normal cellular cholesterol and lipoprotein metabolism is reviewed before describing the disorders, their metabolic derangements and their clinical effects. FH is classified as two simplified phenotypes of disease according to the severity of the metabolic derangement. The dominantly inherited heterozygous phenotype comprises defects in the LDL receptor, apoB100, and neural apoptosis regulatory cleavage protein. The homozygous phenotype is co-dominant in defects of the LDL receptor, and occurs also as the ARH of adapter protein mutations. Defective binding of apoB100 does not result in a significant gene dose effect, but enhances the severity of heterozygotes for LDL receptor mutations. The genetic diagnosis of FH has provided greater accuracy in definition and detection of disease and exposes information about migration of populations. All of these disorders pose a high risk of atherosclerosis, especially in the homozygous phenotype. Studies of influences on the phenotype and responses to treatment are also discussed in the context of the metabolic derangements. PMID:18516203

Marais, A David

2004-01-01

280

Fugitives from the Vesta family  

Microsoft Academic Search

Spectroscopic observations of Asteroid (4) Vesta and numerous members of the Vesta family located in the inner asteroid belt have determined that these objects have reflectance properties of basaltic material. A plausible hypothesis is that the surface of Vesta was punctured by large impacts in the past which dispersed fragments of its basaltic crust into space and produced one of

David Nesvorný; Fernando Roig; Brett Gladman; Daniela Lazzaro; Valerio Carruba; Thais Mothé-Diniz

2008-01-01

281

Family and family therapy in Russia.  

PubMed

This article represents the information about family and family therapy in the context of culture, traditions and contemporary changes of social situations in Russia. The legislation of family rights are mentioned within items about marriage and family in the Constitution, Civil Code and Family Code of the Russian Federation which has changed during recent years. The definition of family and description of family structure are given through the prism of the current demographic situation, dynamics of statistics of marriage and divorce rates, mental disorders, disabilities and such phenomena as social abandonment. The actual curriculum, teaching of family therapy and its disadvantages, system of continuous education, supervision and initiatives of the Institute of Integrative Family Therapy in improvement of preparing of specialists who can provide qualified psychosocial assistance for the family according to the actual needs of society are noted. The directions of state and private practice of family counselling and therapy both for psychiatric patients and medical patients, for adults and children in a family systemic approach are highlighted with an indication of the spectrum of techniques and methods used by Russian professionals. The main obstacles and perspectives of development of family therapy in Russia are summarized. PMID:22515460

Bebtschuk, Marina; Smirnova, Daria; Khayretdinov, Oleg

2012-04-01

282

Family Matters: Kinship in Jane Austen [book chapter  

E-print Network

Families shape the individuals born into them in large and small ways, consciously and unconsciously; but the kinship dynamics that structure power in families are perhaps the most invisible of these forces. I doubt that ...

Perry, Ruth

2009-01-01

283

Impact Of Family Environment On Disordered Eating In Overweight Adolescents.  

National Technical Information Service (NTIS)

Research has shown that overweight and disordered eating are often comorbid especially in the context of poor family functioning and negative affect. The role of family structure remains largely unexplored, and no single study has examined all of these va...

D. A. Ross

2008-01-01

284

Boston University Family Medicine  

E-print Network

Boston University Family Medicine Global Health CollaborativeFamily Medicine As part of the Department of Family Medicine at Boston University, the Collaborative is committed to introducing and improving Family Medicine programs around the world. Family Medicine is a holistic specialty that attends

Spence, Harlan Ernest

285

Family Reading Night  

ERIC Educational Resources Information Center

This book offers clear and practical guidelines to help engage families in student success. It shows families how to conduct a successful Family Reading Night at their school. Family Night themes include Scary Stories, Books We Love, Reading Olympics, Dr. Seuss, and other themes. Family reading nights invite parents to come to school with their…

Hutchins, Darcy; Greenfeld, Marsha; Epstein, Joyce

2007-01-01

286

Strengthening Our Military Families  

MedlinePLUS

... Commitment STRENGTHENING OUR MILITARY FAMILIES 1 ? ? Strengthening Our Military Families: Meeting America’s Commitment “This government-wide review ... Behav Pediatr. 2009;30:271-278 Strengthening Our MilitAry FAMilieS 2 ? ? • civilian family members can live fulfilling ...

287

Segregation of a Latent High Adiposity Phenotype in Families with a History of Type 2 Diabetes Mellitus Implicates Rare Obesity-Susceptibility Genetic Variants with Large Effects in Diabetes-Related Obesity  

PubMed Central

Background We recently reported significantly greater weight gain in non-diabetic healthy subjects with a 1st degree family history (FH+) of type 2 diabetes mellitus (T2DM) than in a matched control group without such history (FH?) during voluntary overfeeding, implying co-inheritance of susceptibilities to T2DM and obesity. We have estimated the extent and mode of inheritance of susceptibility to increased adiposity in FH+. Methods Normoglycaemic participants were categorised either FH+ (?1 1st degree relative with T2DM, 50F/30M, age 45±14 (SD) yr) or FH? (71F/51M, age 43±14 yr). Log-transformed anthropometric measurements (height, hip and waist circumferences) and lean, bone and fat mass (Dual Energy X-ray Absorptiometry) data were analysed by rotated Factor Analysis. The age- and gender-adjusted distributions of indices of adiposity in FH+ were assessed by fits to a bimodal model and by relative risk ratios (RR, FH+/FH?) and interpreted in a purely genetic model of FH effects. Results The two orthogonal factors extracted, interpretable as Frame and Adiposity accounted for 80% of the variance in the input data. FH+ was associated with significantly higher Adiposity scores (p<0.01) without affecting Frame scores. Adiposity scores in FH+ conformed to a bimodal normal distribution, consistent with dominant expression of major susceptibility genes with 59% (95% CI 40%, 74%) of individuals under the higher mode. Calculated risk allele frequencies were 0.09 (0.02, 0.23) in FH?, 0.36 (0.22, 0.48) in FH+ and 0.62 (0.36, 0.88) in unobserved T2DM-affected family members. Conclusions The segregation of Adiposity in T2DM-affected families is consistent with dominant expression of rare risk variants with major effects, which are expressed in over half of FH+ and which can account for most T2DM-associated obesity in our population. The calculated risk allele frequency in FH? suggests that rare genetic variants could also account for a substantial fraction of the prevalent obesity in this society. PMID:23950934

Jenkins, Arthur B.; Batterham, Marijka; Samocha-Bonet, Dorit; Tonks, Katherine; Greenfield, Jerry R.; Campbell, Lesley V.

2013-01-01

288

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

PubMed

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

Shaw, Alison; Hurst, Jane A

2009-04-01

289

The Family in Family Medicine Research.  

ERIC Educational Resources Information Center

If the family physician is to focus on the family as a unit of diagnosis and treatment, new knowledge with practical applications for the health care provided is required. Producing this knowledge is the responsibility of the family medicine researcher who will need to use new tools, strategies, and innovative research design. (JMD)

Froom, Jack; Rosen, Melville G.

1980-01-01

290

Revamping Family Preservation Services for Native Families.  

ERIC Educational Resources Information Center

Examines the philosophy and program structures of family preservation services (FPS) in the context of providing services to Native American families with child welfare issues. Explores Native cultural concepts of family, child rearing, time, and spirituality. Outlines cross-cultural training needs for FPS workers related to cultural awareness,…

Coleman, Heather; Unrau, Yvonne A.; Manyfingers, Brenda

2001-01-01

291

Family Decision Making  

MedlinePLUS

... National Center Homepage Hearing Loss Share Compartir Family Decision Making How can I start communicating with my baby ... Coded English Natural Gestures Speech Speech Reading Family Decision Making Family Adjustment Gathering Information Making Decisions Opinions of ...

292

Family Child Care Licensing Study, 1998.  

ERIC Educational Resources Information Center

This report details a survey of state child care regulatory agencies. Data on both small family child care homes (FCCH) and group or large family child care homes (LCCH or GCCH) are included and organized into 22 categories: (1) number of regulated homes; (2) definitions and regulatory requirements; (3) unannounced inspection procedure; (4)…

Children's Foundation, Washington, DC.

293

Family Child Care Licensing Study, 1997.  

ERIC Educational Resources Information Center

This report details the findings of an annual survey of state child care regulatory agencies. The survey gathered data on both small family child care homes and group or large family child care homes in each of the 50 states, the District of Columbia, Puerto Rico and the Virgin Islands. The report's introduction lists the survey categories and…

Children's Foundation, Washington, DC.

294

FM radio: family interplay with sonic mementos  

Microsoft Academic Search

Digital mementos are increasingly problematic, as people acquire large amounts of digital belongings that are hard to access and often forgotten. Based on fieldwork with 10 families, we designed a new type of embodied digital memento, the FM Radio. It allows families to access and play sonic mementos of their previous holidays. We describe our underlying design motivation where recordings

Daniela Petrelli; Nicolas Villar; Vaiva Kalnikaité; Lina Dib; Steve Whittaker

2010-01-01

295

Familial Encephalopathy with Neuroserpin Inclusion Bodies  

Microsoft Academic Search

We report on a new familial neurodegenerative dis- ease with associated dementia that has presented clin- ically in the fifth decade, in both genders, and in each of several generations of a large family from New York State—a pattern of inheritance consistent with an autosomal dominant mode of transmission. A key pathological finding is the presence of neuronal in- clusion

Richard L. Davis; Peter D. Holohan; Antony E. Shrimpton; Arthur H. Tatum; John Daucher; George H. Collins; Robert Todd; Charles Bradshaw; Paul Kent; David Feiglin; Arthur Rosenbaum; Mark S. Yerby; Cheng-Mei Shaw; Felicitas Lacbawan; Daniel A. Lawrence

1999-01-01

296

Large intestine  

NSDL National Science Digital Library

The large intestine is larger and shorter than the small intestine and connects to the small intestine and the anus. Nutrient deficient material from the small intestine travels through the large intestine to the anus. This material is called feces and is excreted. Feces is made up of material that our bodies cannot break down into smaller parts to be used by the body.

Katie Hale (CSUF;)

2007-08-18

297

A novel seven-base deletion of the CTSC gene identified in a Hungarian family with Papillon-Lefèvre syndrome.  

PubMed

Papillon-Lefévre syndrome (PLS; OMIM 245000) is a rare autosomal recessive condition characterized by symmetrical palmoplantar hyperkeratosis and periodontal inflammation, causing loss of both the deciduous and permanent teeth. PLS develops due to mutations in the cathepsin C gene, CTSC. Recently we have identified a Hungarian PLS family with two affected siblings. Direct sequencing of the coding regions of the CTSC gene revealed a novel seven-base deletion leading to frameshift and early stop codon in the fourth exon of the CTSC gene (c.681delCATACAT, p.T188fsX199). The affected family members carried the mutation in homozygous form, while the clinically unaffected family members carried the mutation in heterozygous form. The unrelated controls carried only the wild type sequence. In this paper we report a novel homozygous deletion of seven bases on the CTSC gene leading to the development of PLS. Since consanguineous marriage was unknown in the investigated family, the presence of the homozygous seven-base deletion of the CTSC gene may suggest that the parents are close relatives. PMID:23397598

Farkas, Katalin; Paschali, Ekaterine; Papp, Ferenc; Vályi, Péter; Széll, Márta; Kemény, Lajos; Nagy, Nikoletta; Csoma, Zsanett

2013-07-01

298

Exclusion of p75NGFR and other candidate genes in a family with hereditary sensory neuropathy type II.  

PubMed

Hereditary sensory neuropathy Type II (HSN II) is an autosomal recessive disorder characterized by the loss of peripheral sensory modalities in individuals with otherwise normal development. Patients with HSN II often have chronic ulceration of the fingers and toes, autoamputation of the distal phalanges, and neuropathic joint degeneration associated with loss of pain sensation. Recent descriptions of a similar phenotype in mice carrying a targeted mutation in the low affinity nerve growth factor receptor, p75NGFR, suggested the possibility that mutations in this gene or other members of the nerve growth factor (NGF) family of genes and their receptors might be responsible for this human disorder. In this study candidate genes were evaluated by their inheritance pattern in two sisters affected with HSN II, their unaffected sister and mother in a consanguineous family. The segregation of polymorphic alleles at and around loci for p75NGFR, TRKA, TRKB, BDNF, and familial dysautonomia (another hereditary sensory neuropathy having features in common with HSN II) virtually excluded these genes as the cause of HSN II in this family. Further evaluation of loci for other neurotrophic factors and their receptors, which will be possible when mapping information on their loci becomes available, may permit the identification of the gene responsible for HSN II. PMID:8895241

Davar, G; Shalish, C; Blumenfeld, A; Breakfield, X O

1996-09-01

299

Strengthening Family Practices for Latino Families  

PubMed Central

The study examined the effectiveness of a culturally-adapted Strengthening Families Program (SFP) for Latinos to reduce risks for alcohol and drug use in children. Latino families, predominantly Puerto Rican, with a 9–12 year old child and a parent(s) with a substance abuse problem participated in the study. Pre- and post-tests were conducted with each family. Parental stress, parent-child dysfunctional relations, and child behavior problems were reduced in the families receiving the intervention; family hardiness and family attachment were improved. Findings contribute to the validation of the SFP with Latinos, and can be used to inform social work practice with Puerto Rican families. PMID:20871785

Chartier, Karen G.; Negroni, Lirio K.; Hesselbrock, Michie N.

2010-01-01

300

The Pfam Protein Families Database  

E-print Network

Pfam is a large collection of protein multiple sequence alignments and profile hidden Markov models. Pfam is available on the WWW in the UK at http://www.sanger.ac.uk/Software/Pfam/ , in Sweden at http://www.cgr.ki.se/Pfam/ and in the US at http:// pfam.wustl.edu/ . The latest version (4.3) of Pfam contains 1815 families. These Pfam families match 63% of proteins in SWISS-PROT 37 and TrEMBL 9. For complete genomes Pfam currently matches up to half of the proteins. Genomic DNA can be directly searched against the Pfam library using the Wise2 package.

Alex Bateman; Ewan Birney; Richard Durbin; Sean R. Eddy; Kevin L. Howe; Erik L. L. Sonnhammer

2000-01-01

301

[The press and family planning].  

PubMed

The treatment in the press of family planning hinges on two fundamental factors: the taboo of the leftist groups and the taboo of the Catholic Church, whose head is against abortion under any circumstances. Leftist views insinuate that family planning is the genocidal plan of North American imperialists against the Third World and, in particular, against Latin America. This genocidal plan is supposed to subject poor populations to international schemes. In the press family planning is often treated in a sanctimonious fashion, lumping it together with topics like pornography, sex, and violence. In 1983 the daily newspaper Expreso published a supplement running every week for almost three months about the issue of population, which dealt fairly extensively with such topics as population and housing, education, employment, and urban proliferation, as well as responsible parenthood and child survival. In addition, there was a detailed description of contraceptive methods. In October 1986 another surprising thing happened: the President of Peru talked about the topic of family planning, which at the time was an act of courage. Since then much has changed; the whole world is interested in family planning and certain aspects of population. Since October 1986 more has been published in this domain than during the preceding 20 years. In contrast, the Church reacted differently to this issue: after some initial caution, the conference of Peruvian bishops attacked all methods of modern contraceptives and private institutions of family planning. The information boom in family planning will certainly continue. At the moment this flood of articles and editorials about the issue is an expression of the anxiety of families related to uncontrolled reproduction and the fear of overpopulation in large cities devoid of minimal services. PMID:12281466

Abraham De D'ornellas, R

1987-01-01

302

Family assessment in the medical setting.  

PubMed

Acute and chronic illness exists in a social context. A biopsychosocial assessment should include an evaluation of the patient's social situation, the nature of the patient's interpersonal connections, and his/her family's functioning. Families can influence health by direct biological pathways, health behavior pathways, and psychophysiological pathways. There are a large number of family-based risks factors as well as many protective relational factors that influence the onset and course of illness. A family assessment is the first step in determining both the need for further intervention and the specific areas of family life that might need to be addressed. A family assessment provides information about the social substrate for the evolution of the presenting complaint as well as information to better understand the patient's problems. There are many ways to assess families, and there are a variety of family assessment instruments to help with the assessments. Clinician will be best served by becoming familiar and comfortable with at least one assessment model that is consistent, structured, and evaluates a wide range of family functions. Such an assessment can be incorporated into routine clinical care. A good family assessment can be therapeutic in and of itself even if the decision is made that no further family intervention is indicated. PMID:22056906

Keitner, Gabor I

2012-01-01

303

FAMILIES FIRST: Keys to Successful Family Functioning Family Roles  

E-print Network

, par- ents are expected to teach, discipline, and provide for their children. And children are expected foR effecTive family funcTioning There are many roles within a family; however, researchers have identified day at school, or fam- ily members supporting one another after the death of a loved one. · Life ski

Liskiewicz, Maciej

304

HomozygosityMapper - an interactive approach to homozygosity mapping  

Microsoft Academic Search

Homozygosity mapping is a common method for mapping recessive traits in consanguineous families. In most studies, applications for multipoint linkage analyses are applied to determine the geno- mic region linked to the disease. Unfortunately, these are neither suited for very large families nor for the inclusion of tens of thousands of SNPs. Even if less than 10 000 markers are

Dominik Seelow; Markus Schuelke; Friedhelm Hildebrandt; Peter Nürnberg

2009-01-01

305

FAMILY MEDICINE* Definition Of  

E-print Network

FAMILY MEDICINE* Definition Of Family medicine is the medical specialty which provides continuing the biological, clinical and behavioral sciences. The scope of family medicine encompasses all ages, both sexes, each organ system and every disease entity. (1986) (2003) Quality Healthcare In Family Medicine Quality

Finley Jr., Russell L.

306

[Teaching about Family Law].  

ERIC Educational Resources Information Center

This issue of "Focus on Law Studies""contains a special emphasis on teaching about law and the family", in the form of the following three articles: "Teaching Family Law: Growing Pains and All" (Susan Frelich Appleton); "The Family Goes to Court: Including Law in a Sociological Perspective on the Family" (Mary Ann Lamanna); and Michael Grossberg's…

Ryan, John Paul, Ed.

1992-01-01

307

Families in Transition .  

ERIC Educational Resources Information Center

Focuses on disrupted families and the role of the school counselor in helping children adjust. Describes characteristics of healthy families, and discusses the transition to the blended family, effects of divorce groups on children's classroom behavior, counseling children in stepfamilies, single-parent families, and parenting strengths of single…

Bundy, Michael L., Ed.; Gumaer, James, Ed.

1984-01-01

308

Family Participation in Policymaking.  

ERIC Educational Resources Information Center

This bulletin focuses on family participation in mental health policymaking and highlights state efforts to increase family involvement. Articles include: (1) "Promoting Family Member Involvement in Children's Mental Health Policy Making Bodies," which describes how different states are promoting family member involvement in various statutory and…

Caplan, Elizabeth, Ed.; Blankenship, Kelly, Ed.; McManus, Marilyn, Ed.

1998-01-01

309

Black Families. Third Edition.  

ERIC Educational Resources Information Center

The chapters of this collection explore the experiences of black families in the United States and Africa, today and in the past. They are: (1) "African American Families: A Historical Note" (John Hope Franklin); (2) "African American Families and Family Values" (Niara Sudarkasa); (3) "Old-Time Religion: Benches Can't Say 'Amen'" (William Harrison…

McAdoo, Harriette Pipes, Ed.

310

FamilySearch  

NSDL National Science Digital Library

Although still in beta phase, this impressive new genealogical resource from the Church of Jesus Christ of Latter-Day Saints (the Mormons) has immediately received the attention and praise of genealogical researchers. The providers have not publicly stated whether the site will offer access to the entirety of their 2 billion name genealogical record repository, but it already contains over 300 million names in two indexes, searchable by ancestor name. Users may also search a host of other genealogy Websites and the site's own SourceGuide of research outlines by keyword. In addition, the site offers a large collection of browseable and searchable categories of genealogical research sites, such as Census and Lists, Land and Property, Migration, Military, Vital Records, and others. Registered users can collaborate with others working on similar projects, add Websites, and have their research preserved in The Pedigree Resource File. While the Internet already holds a multitude of family research sites, when it is complete, FamilySearch will almost certainly be regarded as the first and most comprehensive place to begin a search for one's ancestors.

1999-01-01

311

Singing about family planning.  

PubMed

The Nigerian Family Health services project teamed up with the Johns Hopkins University's Population Communication Services to produce songs called "Choices" and "Wait for Me." The songs, which were about sexual responsibility, were performed by popular music stars King Sunny Ade and Onyeka Onwenu and appeared under King Sonny Ade's long playing albums in 1989. Teaching sexual responsibility through song was suggested in focus group discussions. Findings indicated that young people were responsive to messages about sexual responsibility, postponing sex or saying "no," male sexual responsibility, and children by informed choice and not chance among married couples. An impact assessment of the songs was conducted in February, 1991. Survey findings revealed that 64% of urban and 22% of rural respondents recalled having heard the songs and seen the videos. 48% of urban youth discussed the songs with friends, and 27% discussed the songs with sexual partners. 90% of respondents reported agreement with the message that couples should have only the number of children that they can care for, and that couples should practice family planning. The target population that was affected most by the songs was aged less than 35 years. The strategy of using songs to teach youth responsible parenting appears to be a reliable strategy for mass education and mobilization. There is mass support from among members of the National Council for Women's Societies, the Planned Parenthood Federation of Nigeria, and Coca Cola Corporation, as well as the public at large. PMID:12318626

Emah, E

1993-01-01

312

The lamin protein family  

PubMed Central

Summary The lamins are the major architectural proteins of the animal cell nucleus. Lamins line the inside of the nuclear membrane, where they provide a platform for the binding of proteins and chromatin and confer mechanical stability. They have been implicated in a wide range of nuclear functions, including higher-order genome organization, chromatin regulation, transcription, DNA replication and DNA repair. The lamins are members of the intermediate filament (IF) family of proteins, which constitute a major component of the cytoskeleton. Lamins are the only nuclear IFs and are the ancestral founders of the IF protein superfamily. Lamins polymerize into fibers forming a complex protein meshwork in vivo and, like all IF proteins, have a tripartite structure with two globular head and tail domains flanking a central ?-helical rod domain, which supports the formation of higher-order polymers. Mutations in lamins cause a large number of diverse human diseases, collectively known as the laminopathies, underscoring their functional importance. PMID:21639948

2011-01-01

313

Characteristics of universal embezzling families  

NASA Astrophysics Data System (ADS)

Quantum state embezzlement is the transformation |? >?|? >|? > using only local operations, where |? > and |? > are multipartite quantum states. Exact embezzlement is an impossible task since it implies the increase of entanglement without communication. Surprisingly, van Dam and Hayden [Phys. Rev. A 67, 060302 (2003), 10.1103/PhysRevA.67.060302] find a universal embezzling family of states |? > that enables embezzlement in the bipartite setting with arbitrary precision as the dimension of |? > increases. Furthermore, the family is independent of the state |? > to be embezzled. We study embezzlement in the bipartite setting. We present various requirements and consequences, and infinitely many universal embezzling families inequivalent to that proposed by van Dam and Hayden. We include numerical studies of up to 33-qubit large local systems.

Leung, Debbie; Wang, Bingjie

2014-10-01

314

La maladie de Wilson: à propos d'un cas familial  

PubMed Central

La maladie de Wilson est une maladie rare autosomique récessive due à une diminution de l’élimination du cuivre dans la bile et son accumulation toxique dans les organes en particulier le cerveau, le foie, la cornée et le rein d'où son hétérogénéité clinique. Les manifestations ophtalmologiques représentent des critères diagnostiques importants. Le traitement précoce permet une réversibilité des déficits; non traitée la maladie de Wilson est létale. Nous rapportons un cas familial de la maladie de Wilson: deux membres d'une fratrie issus d'un mariage consanguin étaient atteints de la maladie de Wilson dans ses trois formes cliniques: hépatique, neurologique et psychiatrique. Les manifestations ophtalmologiques de la maladie de Wilson sont l'anneau de Keyser Fleischer et la cataracte en tournesol, l'atteinte hépatique se manifeste par une hépatite chronique et une cirrhose, la symptomatologie neurologique et psychiatrique est variée; on retrouve à l'IRM une atteinte prédominante aux noyaux gris centraux. Le diagnostic positif de la maladie de Wilson est fait sur la triade: présence de l'anneau de Keyser Fleischer, céruloplasmine sanguine basse et augmentation de la cuprurie de 24 heures. Le traitement précoce basé sur les chélateurs de cuivre permet la réversibilité des lésions. Le pronostic dépend de la sévérité de la maladie lors du diagonstic et de la qualité de la prise en charge. Ce cas familial de la maladie de Wilson démontre l'importance du dépistage des membres pré symptomatique par un examen ophtalmologique et général rigoureux.

Mouzari, Yassine; Abdelkhalek, Ryme; El Asri, Fouad; Reda, Karim; Oubaaz, Abedelbarre

2014-01-01

315

Family Allowances and Fertility: Socioeconomic Differences  

PubMed Central

This article explores socioeconomic differences in the effect of family allowances on fertility. Although several studies have examined the relationship between cash benefits and fertility, few studies have addressed the possible differential effects of cash benefits on families of different income or education levels. I reconstructed the birth histories of women in the past two Israeli censuses of 1983 and 1995 to study socioeconomic differences in the effect of family allowances up to the seventh parity. The results indicate that family allowances have a significant effect at every parity. Using female education as an indicator of socioeconomic status, I find that socioeconomic status is a significant modifier of the effect of family allowances. Family allowances seem to have a relatively large impact on more-educated women. PMID:19771939

SCHELLEKENS, JONA

2009-01-01

316

Linkage Analysis in Families with Joubert Syndrome Plus Oculo-Renal Involvement Identifies the CORS2 Locus on Chromosome 11p12-q13.3  

PubMed Central

Joubert syndrome (JS) is an autosomal recessive developmental brain condition characterized by hypoplasia/dysplasia of the cerebellar vermis and by ataxia, hypotonia, oculomotor apraxia, and neonatal breathing dysregulation. A form of JS that includes retinal dysplasia and cystic dysplastic kidneys has been differentiated from other forms of JS, called either “JS type B” or “cerebello-oculo-renal syndrome” (CORS), but the genetic basis of this condition is unknown. Here, we describe three consanguineous families that display CORS. Linkage analysis defines a novel locus on chromosome 11p12-q13.3, with a maximum two-point LOD score of Z=5.2 at the marker D11S1915. Therefore, the cerebello-oculo-renal form of JS is a distinct genetic entity from the Joubert syndrome 1 (JBTS1) locus described elsewhere, in which there is minimal involvement of retina or kidney. We suggest the term “CORS2” for this new locus. PMID:12917796

Keeler, Lesley C.; Marsh, Sarah E.; Leeflang, Esther P.; Woods, Christopher G.; Sztriha, László; Al-Gazali, Lihadh; Gururaj, Aithala; Gleeson, Joseph G.

2003-01-01

317

Familial adenomatous polyposis  

PubMed Central

Familial adenomatous polyposis (FAP) is characterized by the development of many tens to thousands of adenomas in the rectum and colon during the second decade of life. FAP has an incidence at birth of about 1/8,300, it manifests equally in both sexes, and accounts for less than 1% of colorectal cancer (CRC) cases. In the European Union, prevalence has been estimated at 1/11,300-37,600. Most patients are asymptomatic for years until the adenomas are large and numerous, and cause rectal bleeding or even anemia, or cancer develops. Generally, cancers start to develop a decade after the appearance of the polyps. Nonspecific symptoms may include constipation or diarrhea, abdominal pain, palpable abdominal masses and weight loss. FAP may present with some extraintestinal manifestations such as osteomas, dental abnormalities (unerupted teeth, congenital absence of one or more teeth, supernumerary teeth, dentigerous cysts and odontomas), congenital hypertrophy of the retinal pigment epithelium (CHRPE), desmoid tumors, and extracolonic cancers (thyroid, liver, bile ducts and central nervous system). A less aggressive variant of FAP, attenuated FAP (AFAP), is characterized by fewer colorectal adenomatous polyps (usually 10 to 100), later age of adenoma appearance and a lower cancer risk. Some lesions (skull and mandible osteomas, dental abnormalities, and fibromas on the scalp, shoulders, arms and back) are indicative of the Gardner variant of FAP. Classic FAP is inherited in an autosomal dominant manner and results from a germline mutation in the adenomatous polyposis (APC) gene. Most patients (~70%) have a family history of colorectal polyps and cancer. In a subset of individuals, a MUTYH mutation causes a recessively inherited polyposis condition, MUTYH-associated polyposis (MAP), which is characterized by a slightly increased risk of developing CRC and polyps/adenomas in both the upper and lower gastrointestinal tract. Diagnosis is based on a suggestive family history, clinical findings, and large bowel endoscopy or full colonoscopy. Whenever possible, the clinical diagnosis should be confirmed by genetic testing. When the APC mutation in the family has been identified, genetic testing of all first-degree relatives should be performed. Presymptomatic and prenatal (amniocentesis and chorionic villous sampling), and even preimplantation genetic testing is possible. Referral to a geneticist or genetic counselor is mandatory. Differential diagnoses include other disorders causing multiple polyps (such as Peutz-Jeghers syndrome, familial juvenile polyps or hyperplastic polyposis, hereditary mixed polyposis syndromes, and Lynch syndrome). Cancer prevention and maintaining a good quality of life are the main goals of management and regular and systematic follow-up and supportive care should be offered to all patients. By the late teens or early twenties, colorectal cancer prophylactic surgery is advocated. The recommended alternatives are total proctocolectomy and ileoanal pouch or ileorectal anastomosis for AFAP. Duodenal cancer and desmoids are the two main causes of mortality after total colectomy, they need to be identified early and treated. Upper endoscopy is necessary for surveillance to reduce the risk of ampullary and duodenal cancer. Patients with progressive tumors and unresectable disease may respond or stabilize with a combination of cytotoxic chemotherapy and surgery (when possible to perform). Adjunctive therapy with celecoxib has been approved by the US Food and Drug Administration and the European Medicines Agency in patients with FAP. Individuals with FAP carry a 100% risk of CRC; however, this risk is reduced significantly when patients enter a screening-treatment program. PMID:19822006

Half, Elizabeth; Bercovich, Dani; Rozen, Paul

2009-01-01

318

AIDS and the family: families take care.  

PubMed

In 1994, the International Year of the Family, the WHO's Global Program on AIDS (GPA) is marking World AIDS Day under the banner AIDS and the Family. Traditional and non-traditional families have a crucial role to play in addressing the HIV/AIDS pandemic. In the run-up to World AIDS Day--and on 1 December itself--GPA urges the world to focus on how families of all kinds are affected by AIDS, on how they can be more effective in prevention and care, and on how they can contribute to global efforts against the disease. For GPA, any group of people linked by feelings of trust, mutual support and a common destiny may be seen as a family. The concept need not be limited to ties of blood, marriage, sexual partnership or adoption. In this light, religious congregations, workers' associations, support groups of people with HIV/AIDS, gangs of street children, circles of drug injectors, collectives of sex workers and networks of governmental, nongovernmental and intergovernmental organizations may all be regarded as families within the over-arching family of humankind. Every kind of family should take care to protect its members from HIV. And all families should take care of those among them who fall ill with AIDS. Families take care. "Families whose bonds are based on love, trust, nurturing and openness are best placed to protect their members from infection and give compassionate care and support to those affected by HIV or AIDS," says Dr. Hiroshi Nakajima, Director-General of the WHO [World Health Organization]. PMID:12287963

1994-01-01

319

Impact of Migration on African American Family Development and Relationships  

Microsoft Academic Search

This article examines the short-and long-term influences of African American migration on the development and functioning of African American families and family relationships. Using existing research and the results from an ethnographic study of a large, African American, extended family, this article confirms the findings of previous studies and begins to examine the meaning and definition of contemporary types of

Pearl Stewart

2007-01-01

320

Work and Family: 1992. Status Report and Outlook.  

ERIC Educational Resources Information Center

Many parents are currently struggling to balance job and family responsibilities. Such attempts bring about changes in work and individual attitudes. This report presents the status of work and family in 1992, as well as the nature and direction of workplace changes to accommodate families. The report indicates that large United States companies…

Galinsky, Ellen

321

The Arabidopsis Rab GTPase family: another enigma variation  

Microsoft Academic Search

The Arabidopsis genome sequence reveals that gene families such as the Rab GTPase family, which encodes key determinants of vesicle-targeting specificity, are considerably more diverse in plants and mammals than in yeast. In mammals, this diversity appears to reflect the complexity of membrane trafficking. Phylogenetic analyses indicate that, despite its large size, the Arabidopsis Rab family lacks most of the

Stephen Rutherford; Ian Moore

2002-01-01

322

Internet and computer technology hazards: Perspectives for family counselling  

Microsoft Academic Search

Families are increasingly integrating computing technologies into their everyday activities, expanding the range of external influence upon them. For many families, basic notions of 'home' are undergoing shifts as large-scale cultural and economic changes occur that are related to the 'Information age' and as family members spend more time on the Internet and with advanced communications technologies. The Internet is

Jo Ann Oravec

2000-01-01

323

Intergenerational Succession on Family Farms: Evidence from Survey Data  

Microsoft Academic Search

This study examines family farms and characteristics affecting farm succession. Based on a farm survey, three aspects of succession are analysed in the paper: the probability of family succession; the likelihood of having a successor designated; and the timing of succession. Large and specialised farms are more likely to be transferred within the family and to have appointed a successor.

Thomas Glauben; Hendrik Tietje; Christoph R. Weiss

2002-01-01

324

Family Health History and Diabetes  

MedlinePLUS

... Health History and Diabetes Family Health History and Diabetes En español Family health history is an important ... Four Questions You Should Ask Your Family About Diabetes & Family Health History Knowing your family health history ...

325

Family therapy and the Igbo family system.  

PubMed

Theories and treatment modalities may differ in the degree to which they are applicable to different groups. This paper examines the applicability of Bowen's family therapy concepts to a culturally different family system, the Igbo of Southeastern Nigeria. The analyses point to the importance of understanding client value orientations in planning appropriate care. PMID:8081698

Nkongho, N O

1994-01-01

326

Family Network Intervention: Healing Families in Crisis  

ERIC Educational Resources Information Center

Describes a therapeutic approach for helping families relieve a crisis by calling on their extended family of relatives, friends, and neighbors to meet and initiate a healing process leading towards a productive and constructive resolution of their crisis. (Author/RK)

Rueveni, Uri

1976-01-01

327

FMLA: Family & Medical FLA: Family Leave Act  

E-print Network

Leave FCAL: Family Care Act Leave Parental Leave & Leave Without Salary Who is · Faculty (9 month" in order to be eligible for up to 15 days of unpaid leave per deployment) · Women who take leave due FCAL: Family Care Act Leave Parental Leave & Leave Without Salary Leave Restrictions · Runs

Borenstein, Elhanan

328

Conceptualising Family Life and Family Policies.  

ERIC Educational Resources Information Center

The United Nations International Year of the Family 1994 will give policymakers the opportunity to bring together threads of social life that have previously been treated separately. The danger in talking about the concept of "the family" lies both in its abstractness and in its emotional, religious, and political overtones. To avoid this…

Edgar, Don

329

Family Dinner and Adolescent Overweight  

Microsoft Academic Search

Objective: The purpose of this study was to examine both cross-sectional and longitudinal associations between frequency of family dinner and overweight status in a large sample of 9- to 14-year-old children.Research Methods and Procedures: We studied a cohort of 7784 girls and 6647 boys, 9 to 14 years of age at baseline in 1996, participating in the Growing Up Today

Elsie M. Taveras; Sheryl L. Rifas-Shiman; Catherine S. Berkey; Helaine R. H. Rockett; Alison E. Field; A. Lindsay Frazier; Graham A. Colditz; Matthew W. Gillman

2005-01-01

330

Large Scale RNAi Screen Reveals That the Inhibitor of DNA Binding 2 (ID2) Protein Is Repressed by p53 Family Member p63 and Functions in Human Keratinocyte Differentiation*  

PubMed Central

The inhibitor of DNA binding 2, dominant negative helix-loop-helix protein, ID2, acts as an oncogene and elevated levels of ID2 have been reported in several malignancies. Whereas some inducers of the ID2 gene have been characterized, little is known regarding the proteins capable to repress its expression. We developed siRNA microarrays to perform a large scale loss-of-function screen in human adult keratinocytes engineered to express GFP under the control of the upstream region of ID2 gene. We screened the effect of siRNA-dependent inhibition of 220 cancer-associated genes on the expression of the ID2::GFP reporter construct. Three genes NBN, RAD21, and p63 lead to a repression of ID2 promoter activity. Strikingly NBN and RAD21 are playing on major role in cell cycle progression and mitosis arrest. These results underline the pregnant need to silence ID2 expression at transcript level to promote cell cycle exit. Central to this inhibitory mechanism we find p63, a key transcription factor in epithelial development and differentiation, which binds specific cis-acting sequence within the ID2 gene promoter both in vitro and in vivo. P63 would not suppress ID2 expression, but would rather prevent excessive expression of that protein to enable the onset of keratinocyte differentiation. PMID:21478550

Wu, Ning; Castel, David; Debily, Marie-Anne; Vigano, Maria Alessandra; Alibert, Olivier; Mantovani, Roberto; Iljin, Kristina; Romeo, Paul-Henri; Gidrol, Xavier

2011-01-01

331

Dropping Out of High School: The Effects of Family Structure and Family Transitions  

Microsoft Academic Search

We use the 1988, 1990, and 1992 waves of data from the National Education Longitudinal Study to examine the effects of family structure and family transitions on adolescent high school dropout. Our study differs from previous studies by using a large longitudinal sample (N?=?21,420) and applying event history analysis with standard errors corrected for clustered sampling. Our study has two

Chunyan Song; Jennifer Glick

2012-01-01

332

Stewardship vs. Stagnation: An Empirical Comparison of Small Family and Non-Family Businesses &ast  

Microsoft Academic Search

abstract? Two major perspectives can be construed in the literature concerning the nature of family owned businesses (FOBs). The first implies that these enterprises have unique characteristics of stewardship. FOB owners are said to care deeply about the long-term prospects of the business, in large part because their family's fortune, reputation and future are at stake. Their stewardship is said

Danny Miller; Isabelle Le Breton-Miller; Barry Scholnick

2008-01-01

333

Asymptotically Efficient Simulation Of Large Deviation Probabilities.  

National Technical Information Service (NTIS)

Consider a family of probabilities for which the decay is governed by a large deviation principle. To find an estimate for a fixed member of this family, one is often forced to use simulation techniques. Direct Monte Carlo simulation, however, is often im...

A. B. Dieker, M. R. H. Mandjes

2003-01-01

334

Novel CLDN14 Mutations in Pakistani Families With Autosomal Recessive Non-Syndromic Hearing Loss  

PubMed Central

Mutations in the CLDN14 gene are known to cause autosomal recessive (AR) non-sydromic hearing loss (NSHL) at the DFNB29 locus on chromosome 21q22.13. As part of an ongoing study to localize and identify NSHL genes, the ARNSHL segregating in four Pakistani consanguineous families were mapped to the 21q22.13 region with either established or suggestive linkage. Given the known involvement of CLDN14 gene in NSHL, DNA samples from hearing-impaired members from the four families were sequenced to potentially identify causal variants within this gene. Three novel CLDN14 mutations, c.167G>A (p.Trp56?), c.242G>A (p.Arg81His), and c.694G>A (p.Gly232Arg), segregate with hearing loss (HL) in three of the families. The previously reported CLDN14 mutation c.254T>A (p.Val85Asp) was observed in the fourth family. None of the mutations were detected in 400 Pakistani control chromosomes and all were deemed damaging based on bioinformatics analyses. The nonsense mutation c.167G>A (p.Trp56?) is the first stop codon mutation in CLDN14 gene to be identified to cause NSHL. The c.242G>A (p.Arg81His) and c.694G>A (p.Gly232Arg) mutations were identified within the first extracellular loop and the carboxyl-tail of claudin-14, respectively, which highlights the importance of the extracellular domains and phosphorylation of cytoplasmic tail residues to claudin function within the inner ear. The HL due to novel CLDN14 mutations is prelingual, severe-to-profound with greater loss in the high frequencies. PMID:22246673

Lee, Kwanghyuk; Ansar, Muhammad; Andrade, Paula B.; Khan, Bushra; Santos-Cortez, Regie Lyn P.; Ahmad, Wasim; Leal, Suzanne M.

2012-01-01

335

Assessing postpartum family functioning.  

PubMed

The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals. PMID:21253238

Midmer, D; Talbot, Y

1988-09-01

336

Assessing Postpartum Family Functioning  

PubMed Central

The birth of a child requires adaptation and reorganization within the family system in order to accommodate the new family member and to allow the family to continue in its psychosocial development. Knowledge of the normative and transitional changes required at this stage of family life will enhance family practitioners' understanding of some of the common concerns and complaints related to them by various family members during the postpartum period. The Family FIRO model represents a helpful conceptual framework to increase the family physician's understanding of the issues of inclusion, control, and intimacy that are highlighted during the transition to parenthood. The authors briefly present this model and discuss its application to postpartum adjustment and its implications for health-care professionals. PMID:21253238

Midmer, Deana; Talbot, Yves

1988-01-01

337

The Changing American Family.  

ERIC Educational Resources Information Center

Reviews recent statistics which demonstrate how different modern families are from the stereotyped model American nuclear family. Provides suggestions for elementary social studies teachers and includes an annotated bibliography of instructional resources. (JDH)

Joseph, Pamela B.

1986-01-01

338

Families and Fragile Syndrome  

E-print Network

Health and Human Development (NICHD) family album about Fragile X syndrome. As a health research agency, the NICHD family includes not only scientists, researchers, and health care providers, but also children . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Social and emotional

Rau, Don C.

339

EATING DISORDERS FAMILY PROBLEMS  

E-print Network

ANXIETY DEPRESSION EATING DISORDERS FAMILY PROBLEMS GENERAL CONCERNS INTERPERSONAL DIFFICULTIES.946.5117 Counselling and Cyber Counselling Services to Help With: · Anxiety · Depression · Eating disorders · Family

Toronto, University of

340

Efficient haplotyping for families  

E-print Network

Hapi is a novel dynamic programming algorithm for haplotyping nuclear families that outperforms contemporary family-based haplotyping algorithms. Haplotypes are useful for mapping and identifying genes which cause and ...

Williams, Amy Lynne, Ph.D. Massachusetts Institute of Technology

2010-01-01

341

Family Outcomes: Policy & Practice  

E-print Network

Government Performance and Results Act (1993) APR Program goal: Enhance the development of infants and toddlers (0-3) with disabilities and support their families in meeting their special needs 1 Family Indicator: The percentage of families participating... Kansas Division of Early Childhood February 24, 2005 Family Outcomes: Policy & Practice Jean Ann Summers PhD, Beach Center on Disability Nina Zuna Doctoral Student, Beach Center on Disability Kerry Lida Doctoral Student, Beach Center...

Zuna, Nina

2005-05-05

342

Immigrant Families in Australia  

Microsoft Academic Search

Australia has a larger and more diverse immigrant population than most Western societies. Australia's immigration history is linked to the story of family migration as Australia sought immigrants for permanent settlement. However, it is important to aviod over-generalisation when studying immigrant families in Australia today. The main hypothesis is that in order to understand the immigrant family in Australia today

Jock Collins

1992-01-01

343

The Family Farm Project  

NSDL National Science Digital Library

Kenyon College's Family Farm Project, "a three-year study exploring family farming and community life in Knox County, Ohio," presents an intimate multimedia view of the daily life of the family farm, which some consider a vanishing institution in America.

1996-01-01

344

Strengthening America's Families.  

ERIC Educational Resources Information Center

Improving parenting practices and the family environment is the most effective, enduring strategy for combating juvenile delinquency. Describes the Office of Juvenile Justice and Delinquency Prevention's Strengthening America's Families Initiative. Highlights several family-focused prevention programs identified as exemplary, explaining how they…

Alvarado, Rose; Kumpfer, Karol

2000-01-01

345

Treatment of violent families.  

PubMed Central

Family violence is responsible for a significant proportion of homicides, a major cause of premature deaths in African-Americans. This article reviews the prevalence of family violence and explores associated risk factors. Principles and tips of treatment, along with a cognitive framework to guide the actual therapy, are outlined. Finally, issues of preventing family violence are discussed. PMID:2038079

Bell, C. C.; Chance-Hill, G.

1991-01-01

346

Families in Transition.  

ERIC Educational Resources Information Center

This issue of "Emphasis" deals with families in transition, providing some model programs for the new family and some historical perspectives on how families have developed over time. Articles include: (1) "Nostalgia on the Right" (Nancy Theriot); (2) "Heart to Heart" (Nancy Harrington-MacLennan); (3) "The Media Get the Message" (Janet Alyn); (4)…

Britton, Patti O., Ed.; McGee, Michael, Ed.

1987-01-01

347

The Resiliency of Families.  

ERIC Educational Resources Information Center

According to researchers, the family may be changing but it is still one of the central institutions in society. Studies report a shift in more than 20 attitudes and values, most of which relate to the context of family life. Specifically, these include attitudes toward marriage, divorce, childbearing, childrearing, working women, family violence,…

Morrison, T. R.

348

Families and Assisted Living*  

PubMed Central

Purpose Despite growing research on assisted living (AL) as a residential care option for older adults, the social ramifications of residents' transitions to assisted living is relatively unexplored. This article examines family involvement in AL, including family structures of residents, types of involvement from family members living outside the AL, and outcomes for these family members. Design and Methods We reviewed current literature utilizing the MEDLINE, PSYCINFO, and CINAHL databases to identify AL studies that examined issues pertaining to families or informal care. Following the screening of abstracts, 180 reports were retrieved for further review, and 62 studies were selected for inclusion. Results Families visit residents frequently and provide a wide range of instrumental assistance but provide only minimal personal care. Studies of family outcomes indicated relatively high satisfaction, but potential care burden as well. Implications How family care and involvement occurs in AL in relation to formal care provision and whether various types of formal-informal care integration influence family outcomes remains unclear. We suggest a research agenda that attempts to tease out causal relationships for family involvement, differentiate family roles, and implement longitudinal analyses for a range of family outcomes. PMID:18162571

Gaugler, Joseph E.; Kane, Robert L.

2008-01-01

349

Marriage and Family Counseling.  

ERIC Educational Resources Information Center

Provides an overview of marriage and family counseling, including the growth of interest in this specialty within the American Counseling Association (ACA). Discusses the evolution of marriage and family counseling within ACA, standards for training, credentialing, and unique ethical considerations when counseling couples and families. (Author)

Smith, Robert L.; And Others

1995-01-01

350

Discovering “Family” Creatively  

Microsoft Academic Search

Creativity is a powerful force within the family therapy field, central not only to the therapeutic process but also to counselor education. Time-honored tools, such as the genogram along with its many adaptations, remain useful in learning about family. However, as our rapidly changing culture continually redefines and stretches the concept of family, we must learn new methods to discover

Colleen M. Connolly

2006-01-01

351

Year of the Family.  

ERIC Educational Resources Information Center

This special issue focuses on problems and challenges confronting the California family and on research and extension efforts to provide at least partial answers. Research briefs by staff include "Challenges Confront the California Family" (state trends in poverty, divorce, single-parent families, child abuse, delinquency, teen births, limited…

California Agriculture, 1994

1994-01-01

352

Doing Better for Families  

ERIC Educational Resources Information Center

All OECD governments want to give parents more choice in their work and family decisions. This book looks at the different ways in which governments support families. It seeks to provide answers to questions like: Is spending on family benefits going up, and how does it vary by the age of the child? Has the crisis affected public support for…

OECD Publishing (NJ3), 2011

2011-01-01

353

Fatherhood and Family Support.  

ERIC Educational Resources Information Center

On the assumption that fathers have been relatively absent from family support programs, this publication of the Family Resource Coalition addresses the role of fathers in family support programs, examines the impact of fathers on their children, and describes programs involving fathers successfully. Articles include: (1) "What's Behind the…

Goetz, Kathy, Ed.

1996-01-01

354

Families for All Children.  

ERIC Educational Resources Information Center

This bulletin reflects the commitment of Syracuse University's Center on Human Policy to the idea that children belong with families. The bulletin contains a policy statement which recommends; that all children, regardless of disability, belong with families and need enduring relationships with adults; that families with severely disabled children…

Shoultz, Bonnie, Ed.; Kalyanpur, Maya, Ed.

355

Learning from Latino Families  

ERIC Educational Resources Information Center

As a researcher in parent engagement in school and former parent activist, the author shares three lessons for sparking more authentic partnerships between schools and immigrant families. First, schools need to move away from deficit thinking and validate families' cultures. In the case of Latino immigrant families, this entails understanding…

Auerbach, Susan

2011-01-01

356

Family Customs and Traditions.  

ERIC Educational Resources Information Center

Recognizing the importance of maintaining open communication with immediate and extended family members, this book provides a compilation of ideas for family traditions and customs that are grounded in compassion and human kindness. The traditions were gathered from families in the United States and Canada who responded to advertisements in…

MacGregor, Cynthia

357

Single Parent Families  

Microsoft Academic Search

Major changes are taking place in American and Cana- dian families exerting dramatic influences on family life and the pro- fessional of nursing. This was a recently completed project involving a multidisciplinary team of scholars from across North America that brought together the latest information available on a wide variety of single parent families. The purpose of this chapter is

Shirley M. H. Hanson; Marsha L. Heims; Doris J. Julian; Marvin B. Sussman

1994-01-01

358

Family Support Evaluation.  

ERIC Educational Resources Information Center

The Family Resource Coalition of America (FRCA) and the National Resource Center for Family Centered Practice convened a meeting of evaluators, policymakers, and program practitioners to discuss the issue of evaluation in the field of family support. The goal was to bring together those who were implementing programs, evaluating programs, and…

Lalley, Jacqueline, Ed.; Ahsan, Nilofer, Ed.

1998-01-01

359

The Family Leukemia Association  

ERIC Educational Resources Information Center

An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

Pollitt, Eleanor

1976-01-01

360

Family Issues for the Nineties.  

ERIC Educational Resources Information Center

This presentation reviews the characteristics of the Canadian family at present. Discussion focuses on divorce, family structure, reproductive technology, fertility, family size, family mobility, family support, government role, women's participation in the labor force, daily family routines, television viewing, work and the family, the need for…

Mirabelli, Alan

361

Nontraditional families and childhood progress through school  

Microsoft Academic Search

I use U.S. census data to perform the first large-sample, nationally representative tests of outcomes for children raised\\u000a by same-sex couples. The results show that children of same-sex couples are as likely to make normal progress through school\\u000a as the children of most other family structures. Heterosexual married couples are the family type whose children have the\\u000a lowest rates of

Michael J. Rosenfeld

2010-01-01

362

Large Nc  

NASA Astrophysics Data System (ADS)

The 1/Nc expansion of QCD with Nc = 3 has been successful in explaining a wide variety of QCD phenomenology. Here I focus on the contracted spin-flavor symmetry of baryons in the large-Nc limit and deviations from spin-flavor symmetry due to corrections suppressed by powers of 1/Nc. Baryon masses provide an important example of the 1/Nc expansion, and successful predictions of masses of heavy-quark baryons continue to be tested by experiment. The ground state charmed baryon masses have all been measured, and five of the eight ground state bottom baryon masses have been found. Results of the 1/Nc expansion can aid in the discovery of the remaining bottom baryons. The brand new measurement of the ?b- mass by the CDF collaboration conflicts with the original D0 discovery value and is in excellent agreement with the prediction of the 1/Nc expansion.

Jenkins, Elizabeth E.

2009-12-01

363

An autosomal recessive form of spastic cerebral palsy (CP) with microcephaly and mental retardation.  

PubMed

Cerebral palsy (CP) is defined as any nonprogressive motor deficits resulting from cerebral abnormalities that occur in the prenatal or perinatal period. Symptoms become apparent during the first year of life. Genetic forms of CP account for about 2% in European populations but are thought to cause a substantial proportion in consanguineous families. We have identified a large consanguineous family from Oman with spastic diplegia, microcephaly, and mental retardation. Additional manifestations include hyperreflexia, clumsiness, unstable gait, drooling, and dysarthria. There was phenotypic variability among different individuals, but spastic diplegia, microcephaly, and mental retardation were three constant traits present in all affected individuals. PMID:16761294

Rajab, Anna; Yoo, Seung-Yun; Abdulgalil, Aiman; Kathiri, Salem; Ahmed, Riaz; Mochida, Ganeshwaran H; Bodell, Adria; Barkovich, A James; Walsh, Christopher A

2006-07-15

364

Trauma therapy for death row families.  

PubMed

The family members of death row inmates undergo unique suffering that includes disenfranchised grief and intense psychological trauma. In Texas, where executions occur at a rate of 1 every 2 weeks, this class of trauma victims presumably is large, a fact that should generate public mental health concern. Yet the class remains virtually unknown to the therapeutic community. Very little has been done to address the trauma healing needs of death row families. This theoretical paper proposes that structural therapy designed to reengage attachment relationships and reempower family members' innate resources to emotionally regulate one another may provide one of the most effective means of helping this population survive trauma. PMID:21967176

Long, Walter C

2011-01-01

365

The Family Systems Assessment Tool  

Microsoft Academic Search

In this article, we describe the properties of the Family Systems Assessment Tool (FSAT), a self-report instrument designed to assess aspects of relationships and intergenerational family dynamics within a subject’s current family and family of origin.

W. Perry Dickinson; Frank V. deGRUY; L. Miriam Dickinson; H. S. Mullins; Scott Acker; Vince Gilmer

1996-01-01

366

The Research Domain of Family Medicine  

PubMed Central

This article characterizes the large research domain of family medicine. It is a domain that can be productively explored from different perspectives, including: (1) the ecology of medical care and its focus on the environments of health care and interactions among them; (2) the realm of causation and important opportunities to discover how people lose and regain their health; (3) knowing medicine in different ways, focusing on what things mean in the inner and outer realities of individuals and groups of individuals; (4) the nature of the work of family physicians, such as first-contact care for any type of problem, sticking with patients regardless of their diagnoses, incorporating context into decision making, development of relevant technologies, articulating useful theory, and measuring what happens in family medicine; (5) the standard research categories of basic, clinical, health services, health policy, and educational research; and (6) thinking of family medicine research as both a linear process of translation and a wheel of knowledge with iterative loops of discovery that come from within family medicine. The domain of family medicine research is important and ripe for fuller discovery, and it invites the thinking and imagination of the best investigators. It seems unlikely that medical research can ever be complete without a robust family medicine research enterprise. As the domain of family medicine research is explored, not a few, but billions of people will benefit. PMID:15655084

Green, Larry A.

2004-01-01

367

Molecular characterization of Tunisian families with abetalipoproteinemia and identification of a novel mutation in MTTP gene  

PubMed Central

Background Abetalipoproteinemia (ABL; OMIM 200100) is a rare monogenic disorder of lipid metabolism characterized by reduced plasma levels of total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and almost complete absence of apolipoprotein B (apoB). ABL results from genetic deficiency in microsomal triglyceride transfer protein (MTP; OMIM 157147). In the present study we investigated two unrelated Tunisian patients, born from consanguineous marriages, with severe deficiency of plasma low-density lipoprotein (LDL) and apo B. Methods Intestinal biopsies were performed and The MTTP gene was amplified by Polymerase chain reaction then directly sequenced in patients presenting chronic diarrhea and retarded growth. Results First proband was homozygous for a novel nucleotide deletion (c. 2611delC) involving the exon 18 of MTTP gene predicted to cause a non functional protein of 898 amino acids (p.H871I fsX29). Second proband was homozygous for a nonsense mutation in exon 8 (c.923 G?>?A) predicted to cause a truncated protein of 307 amino acids (p.W308X), previously reported in ABL patients. Conclusions We discovered a novel mutation in MTTP gene and we confirmed the diagnosis of abetalipoproteinemia in new Tunisian families. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8134027928652779. PMID:23556456

2013-01-01

368

Description of Clerkships FAMILY MEDICINE  

E-print Network

Description of Clerkships FAMILY MEDICINE Department of Family Medicine #12;2 Family Medicine the dimensions of the role of the family physician and the problem-solving approach of family medicine, community Normally six students rotate monthly in the Department of family medicine. Students receive didactic

Shihadeh, Alan

369

The Growth of a Family  

PubMed Central

Caring for a family during pregnancy and birth is an ideal opportunity for family physicians to assess family functioning and help the family adjust to the birth of a new child. Stress and support systems can influence the course of pregnancy, including obstetric and perinatal outcomes. A family-centered approach can help patients during this critical stage of family development. PMID:21229107

Carroll, June C.; Biringer, Anne

1991-01-01

370

Familial germ cell tumor  

PubMed Central

Familial testicular germ cell tumors are well known in literature. Only few cases are reported where both brother and sister of the same family suffered from germ cell malignancies. We present a family where the proband is a survivor of ovarian dysgerminoma stage IA. Her elder male sibling became acutely ill and was detected to have disseminated testicular malignancy with grossly elevated markers and vegetations in the mitral valve leaflets. Despite all measures he could not be saved. Presence of germ cell malignancies in the siblings of different sex in the same family points toward a genetic susceptibility. Literature review revealed only six similar cases. A discussion regarding the rare occurrence of familial germ cell malignancies with the affected family members may be worthwhile. PMID:22754236

Cyriac, Sanju; Rajendranath, Rejeev; Louis, A Robert; Sagar, T. G.

2012-01-01

371

Why families matter.  

PubMed

Serious illness puts pressure not only on individual family members but also on the family itself. The care of an acutely ill child requires the family to channel many of its resources toward a single member--an arrangement that can usually be sustained for a while but that cannot continue indefinitely while the other members do without. Illness disrupts ordinary familial functions and, if it is serious enough, threatens to break the family altogether. In this article, I argue that there are situations in which the threat to family integrity is so real and serious that the interests of parents or siblings or sometimes grandparents may override the interests of the pediatric patient. PMID:25274881

Lindemann, Hilde

2014-10-01

372

Robertsonian translocation between chromosomes (no.21/14) in relation to the history of spontaneous abortion in a family  

PubMed Central

Background: Approximately 205 million pregnancies occur each year in the worldwide. On the other hand, Spontaneous abortion has been reported in 15-20% of all diagnosed pregnancies. The most common cause of spontaneous abortion is chromosomal abnormalities of the embryo. Robertsonian translocation carriers specially 21-14 are the most common balanced rearrangement among the carrier couples with the history of spontaneous abortion. In order to search for balanced chromosomal rearrangement and cytogenetic disorders, 10 members of related family with consanguinity marriage with the history of recurrent miscarriage were assessed. Case: Cytogenetic evaluation on the basis G-banding technique at high resolution was performed in 3 couples and their related family with the history of idiopathic RSA in order to postulate any balanced chromosomal rearrangement. Conclusion: six members of them appeared with robertsonian balanced translocation between chromosome No.21 to No. 14 with the karyotype of 45, XX, t (14, 21) and 45, XY, t (14, 21), which this results are in agreement with several similar works which claimed that the risk of spontaneous abortion in couples with balanced chromosomal rearrangements is higher compared with general population. Considering to results of present study, it seems as if the cytogenetic analysis of couples with the history of recurrent abortions should be suggested compulsory to estimate the probable presence of any chromosomal rearrangement. This offer wills valuable information for genetic consulting.

Hasanzadeh-NazarAbadi, Mohammad; Baghbani, Fatemeh; Namazi, Iman; Mirzaee, Salmeh

2014-01-01

373

Handy Family Tree  

NSDL National Science Digital Library

In this bilingual (English/Spanish) activity, learners create family trees by tracing the hands of their family members. Learners list inherited traits like eye color, freckles, and chin shape on the fingers of the left hands and list learned traits like favorite foods, games, and pets on the fingers of the right hands. Learners assemble the hands to form trees. Use this family activity to help learners distinguish between inherited and learned traits.

Utah, University O.

2006-01-01

374

Neighborhoods and Families  

Microsoft Academic Search

\\u000a Neighborhoods have a profound impact on children and their families, including health and safety, educational attainment,\\u000a child maltreatment risk, and many others. Yet, surprisingly little is known about the specific mechanisms through which neighborhood\\u000a physical and social characteristics features influence child and family outcomes. This chapter looks at current definitions\\u000a for community and family and reviews research for community effects

James R. McDonell

375

Supporting Family Choice  

Microsoft Academic Search

Supporting family choice in the decision-making process is recommended practice in the field of early childhood and early\\u000a childhood special education. These decisions may relate to the medical, educational, social, recreational, therapeutic\\/rehabilitative,\\u000a and community aspects of the child's disability. Although this practice conveys the message that families are the primary\\u000a decision-makers for their children, families are not always adequately supported

Mary M. Murray; Kimberly A. Christensen; Gardner T. Umbarger; Karin C. Rade; Kathryn Aldridge; Judith A. Niemeyer

2007-01-01

376

The family lecture.  

PubMed

SUMMARY This paper describes a lecture about my extended family, in which I discuss a variety of configurations consisting of lesbian, gay, and bisexual adults, and our children. It raises an array of issues, including alternative insemination, biological and nonbiological parentage, donors and birthmothers, adoption, co-parenting and blended families, significant others, and gay marriage and domestic partnership. It helps many students obtain both a more expansive sense of family and adeeper understanding of homophobia. PMID:24804601

Rose, Nancy E

2002-10-01

377

Managing a Family Budget  

E-print Network

is the foundation of a sound financial management plan. When used in conjunction with records of actual spending, a family budget allows you to pinpoint unnecessary spending and areas where actual costs may be higher or lower than you previously thought. Given... the tight profit margins in agriculture, adhering to a finely tuned family budget can give a much needed boost to your financial future. Not having a family budget means you are not managing your family finances. This most often leads to spending more...

McCorkle, Dean; Klinefelter, Danny A.

2008-09-16

378

Family leisure, family photography and zoos: exploring the emotional geographies of families  

Microsoft Academic Search

In this paper we explore the significance of the zoo as a place for family leisure and the emotional work of sustaining a positive family life. Zoos are understood as culturally laden places, widely identified as locations for family-friendly leisure and as stages for practicing family and then capturing and memorializing this behavior in and through family photographs. Zoo family

Bonnie C. Hallman; S. Mary P. Benbow; P. Benbow

2007-01-01

379

Family Fitness = Family Fun! Presented by  

E-print Network

of the distraction) · According to the A.C. Nielsen Co., the average American watches more than 4 hours of TV each are you exercising now? Six out of ten American adults don't exercise regularly despite the proven TV · At least 40 percent of families watch TV while eating dinner! (And tend to eat more as a result

380

Expanding phenotypic spectrum of familial comedones.  

PubMed

Familial comedones is a rare autosomal dominant disorder characterized by thousands of comedones developing in teens. Some pits or inflammatory lesions may coexist. Only 32 patients from three families have previously been reported. We report herein 12 cases in two unrelated families with familial comedones. Clinical manifestations among members in the same family vastly vary from scattered comedones on the face, trunk, upper and lower extremities to generalized thousands of open comedones, a large number of skin pits and acneiform inflammatory lesions over the entire body. Additionally, multiple severe purulent nodules and abscesses that leave unsightly scars similar to those of hidradenitis suppurativa are observed. Lesions of long-standing inflammation in two patients had developed into squamous cell carcinoma with a poor prognosis. The phenotypic spectrum of familial comedones varies to a large degree. Most importantly, there is potential for some long-standing inflammatory lesions to develop into squamous cell carcinoma. Extra vigilance in surveillance and prompt treatment for such lesions are recommended. PMID:24818872

Rerknimitr, Pawinee; Korkij, Wiwat; Wititsuwannakul, Jade; Panmontha, Wipa; Suphapeetiporn, Kanya; Shotelersuk, Vorasuk

2014-01-01

381

Family History Resources.  

ERIC Educational Resources Information Center

The 12 articles in this issue focus on the theme of family history resources: (1) "Introduction: Family History Resources" (Joseph F. Shubert); (2) "Work, Credentials, and Expectations of a Professional Genealogist" (Coreen P. Hallenbeck and Lewis W. Hallenbeck); (3) "Computers and Genealogy" (Theresa C. Strasser); (4) "Finding Historical Records…

Bookmark, 1991

1991-01-01

382

[Inclusive Recreation and Families.  

ERIC Educational Resources Information Center

This feature issue focuses on inclusive recreation for persons with developmental disabilities and their families. The articles provide information about the benefits of inclusive recreation for individuals and families, the challenges in attempting to create or access community recreation services that offer inclusive programs, and strategies…

Heyne, Linda A., Ed.; And Others

1996-01-01

383

Golden Matrix Families  

ERIC Educational Resources Information Center

This student research project explores the properties of a family of matrices of zeros and ones that arises from the study of the diagonal lengths in a regular polygon. There is one family for each n greater than 2. A series of exercises guides the student to discover the eigenvalues and eigenvectors of the matrices, which leads in turn to…

Fontaine, Anne; Hurley, Susan

2011-01-01

384

Uninsured Rural Families  

ERIC Educational Resources Information Center

Context: Although research shows higher uninsured rates among rural versus urban individuals, prior studies are limited because they do not examine coverage across entire rural families. Purpose: This study uses the Medical Expenditure Panel Survey (MEPS) to compare rural and urban insurance coverage within families, to inform the design of…

Ziller, Erika C.; Coburn, Andrew F.; Anderson, Nathaniel J.; Loux, Stephenie L.

2008-01-01

385

Family Bonding with Universities  

ERIC Educational Resources Information Center

One justification offered for legacy admissions policies at universities is that that they bind entire families to the university. Proponents maintain that these policies have a number of benefits, including increased donations from members of these families. We use a rich set of data from an anonymous selective research institution to investigate…

Meer, Jonathan; Rosen, Harvey S.

2010-01-01

386

Family Reunification Project.  

ERIC Educational Resources Information Center

Utah's Department of Human Services' Family Reunification Project was initiated to demonstrate that intensive, time-limited, home-based services would enable children in foster care to return to their natural families more rapidly than regular foster care management permits. The following steps were taken in project development: (1) sites were…

Administration for Children, Youth, and Families (DHHS), Washington, DC.

387

Marinating the Family.  

ERIC Educational Resources Information Center

Describes the New York Aquarium's program specifically designed for family learning and teaching. The program's goal is to create an environment where child-parent roles are dropped and where the philosophy that no one of us is as smart as all of us prevails. Strategies for family involvement are outlined. (MH)

Hensel, Karen A.

1982-01-01

388

Black Families. Interdisciplinary Perspectives.  

ERIC Educational Resources Information Center

Since the early 1960s, the black family has been characterized as pathological. This six-part collection of 18 research studies presents alternative approaches to understanding the special characteristics of black families. Part I, "Theoretical and Methodological Perspectives," comprises a comparison of the pioneering work of W. E. B. Du Bois and…

Cheatham, Harold E., Ed.; Stewart, James B., Ed.

389

Families Orientation Tudor Fieldhouse  

E-print Network

with us today, and others have a half dozen more at home. Some of you are dropping off the third generation of Rice students in your family, and some of you are dropping off the first person in your family said "setting a good example for children takes all the fun out of middle age." If the child you

Alvarez, Pedro J.

390

Employers, Families and Education.  

ERIC Educational Resources Information Center

Family involvement in education is good for business, critical to children's school achievement, and important in creating strong and vibrant communities. This report discusses the role of businesses and employers in helping partners and family members be more involved in children's learning. Throughout the report, programs at specific companies…

Partnership for Family Involvement in Education (ED), Washington, DC.

391

Family Perspectives on Prematurity  

ERIC Educational Resources Information Center

In this article, seven families describe their experiences giving birth to and raising a premature baby. Their perspectives vary, one from another, and shift over time, depending on each family's circumstances and the baby's developmental course. Experiences discussed include premature labor, medical interventions and the NICU, bringing the baby…

Zero to Three (J), 2003

2003-01-01

392

Military Family Counselling.  

National Technical Information Service (NTIS)

The purpose of this study was to demonstrate the efficacy of family counselling with families of active duty senior non-commissioned officers. It was an application of elements of the Bo-Between Process (Zuk, 1972, 1975) which was based on the finding tha...

J. J. Garrigan

1983-01-01

393

Families living with HIV  

Microsoft Academic Search

Given the historical emergence of the AIDS epidemic first among gay men in the developed world, HIV interventions have primarily focused on individuals rather than families. Typically not part of traditional family structures, HIV-positive gay men in Europe and the US lived primarily in societies providing essential infrastructure for survival needs that highly value individual justice and freedom. Interventions were

M. J. Rotheram-Borus; D. Flannery; E. Rice; P. Lester

2005-01-01

394

Engaging Families with Technology  

ERIC Educational Resources Information Center

How to involve families in the formal education of their children is a question researchers and educators have been trying to answer since the first bricks were laid for the nation's public education system. A solution must be found, for family involvement has been proven to be associated with a myriad of stellar outcomes, including greater…

T.H.E. Journal, 2003

2003-01-01

395

THE JAPANESE ADVERTISING FAMILY  

Microsoft Academic Search

This paper deals with the representation of the family in Japanese TV commercials. Based on empirical research conducted in 2004 and 2005, it argues that Japanese commercials tend to depict the family and its members in highly stereotypical ways. Mothers are almost always shown doing some kind of house- work, at times supported by their daughters, preparing for their future

Michael Prieler

396

Reaching Rural Families.  

ERIC Educational Resources Information Center

This newsletter issue focuses on programming undertaken to address the health and educational needs of rural families in developing and developed nations. After examining the nature of rural families and rural poverty, the newsletter discusses: (1) the Mon Women's Organization in Thailand; (2) The "Contact With Kids" parent education project in…

Bernard van Leer Foundation Newsletter, 1995

1995-01-01

397

Experimental family services  

Microsoft Academic Search

This paper describes a survey of 127 special services for families. Although varying in their methods, all concentrate on the needs of the family as a unit, rather than as individuals. The projects are all innovative. Many use self help methods, involve peer group leadership, or involve users in the organisation of the work. The projects are shown to have

Miriam Richardson; Barry Knight

1981-01-01

398

Patent Family Databases.  

ERIC Educational Resources Information Center

Reports on retrieval of patent information online and includes definition of patent family, basic and equivalent patents, "parents and children" applications, designated states, patent family databases--International Patent Documentation Center, World Patents Index, APIPAT (American Petroleum Institute), CLAIMS (IFI/Plenum). A table noting country…

Simmons, Edlyn S.

1985-01-01

399

Brief Strategic Family Therapy  

Microsoft Academic Search

Homework tasks are an essential com ponent of BSFT. Therapists strategically implement tasks to achieve improvements in family interactions that are directly related to the prevention or reduction of adolescent behavior problems. The use of tasks in BSFT is consistent with the model?s emphasis on having family members ?do? rather than simply ?talk about.? Tasks are assigned based on the

Michael S. Robbins; Jose’ Szapocznik; Gonzalo Pe’rez

400

Firearms and family violence.  

PubMed

Firearms contribute significantly to morbidity and mortality in family violence. This article discusses the debate on gun use for protection and guns in the home. Weapons-related risks in the setting of intimate partner violence are closely reviewed. Recommendations for physicians are discussed in the context of firearms and family violence. PMID:10516848

Kellermann, A; Heron, S

1999-08-01

401

Prosocial family therapy  

Microsoft Academic Search

This manual for Prosocial Family Therapy (PFT) describes a practical method of multisystemic care for juvenile offenders based on our theories about risk and protection factors and therapy process. The PFT team integrates specific parent training techniques and nonspecific family therapy strategies in meetings scheduled with decreasing frequency over a 3-month intervention and 2-year follow-up period. The PFT manual blends

Elaine A Blechman; Kevin D Vryan

2000-01-01

402

Homozygosity mapping reveals new nonsense mutation in the FAM161A gene causing autosomal recessive retinitis pigmentosa in a Palestinian family  

PubMed Central

Purpose: Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal degenerations caused by mutations in at least 45 genes. Recently, the FAM161A gene was identified as the causative gene for RP28, an autosomal recessive form of RP. Methods: We performed a clinical and molecular genetic study of a consanguineous Palestinian family with two three siblings affected with retinitis pigmentosa. DNA samples were collected from the index patient, his father, his affected sister, and two non-affected brothers. DNA sample from the index was subjected to high resolution genome-wide SNP array. Assuming identity-by-descent in this consanguineous family we applied homozygosity mapping to identify disease causing genes. Results: The index patient reported night blindness since the age of 20 years, followed by moderate disease progression with decrease of peripheral vision, the development of photophobia and later on reduced central vision. At the age of 40 his visual acuity was counting fingers (CF) for both eyes, color discrimination was not possible and his visual fields were severely constricted. Funduscopic examination revealed a typical appearance of advanced RP with optic disc pallor, narrowed retinal vessels, bone-spicule like pigmentary changes in the mid-periphery and atrophic changes in the macula. His younger affected brother (37 years) was reported with overall milder symptoms, while the youngest sister (21 years) reported problems only with night vision. Applying high-density SNP arrays we identified several homozygous genomic regions one of which included the recently identified FAM161A gene mutated in RP28-linked autosomal recessive RP. Sequencing analysis revealed the presence of a novel homozygous nonsense mutation, c.1003C>T/p.R335X in the index patient and the affected sister. Conclusion: We identified an RP28-linked RP family in the Palestinian population caused by a novel nonsense mutation in FAM161A. RP in this family shows a typical disease onset with moderate to rapid progression into severe visual impairment including central vision in the index and overall milder symptoms in the younger brother and sister. PMID:24520187

Zobor, Ditta; Balousha, Ghassan; Baumann, Britta

2014-01-01

403

Asteroid families, dynamics and astrometry  

NASA Technical Reports Server (NTRS)

The proper elements and family assignments for the 1227 Palomar-Leiden Survey asteroids of high quality were tabulated. In addition to the large table, there are also auxiliary tables of Mars crossers and commensurate objects, histograms of the proper element distributions, and a discussion. Probably the most important part of the discussion describes the Mars crossing boundary, how the closest distances of approach to Mars and Jupiter are calculated, and why the observed population of Mars crossers should bombard that planet episodically rather than uniformly. Analytical work was done to derive velocity distributions of family forming events from proper element distributions subject to assumptions which may be appropriate for cratering events. Software was developed for a microcomputer to permit plotting of the proper elements. Three orthogonal views are generated and stereo pairs can be printed when desired. This program was created for the study of asteroid families. The astrometry task is directed toward measuring and reducing positions on faint comets and the minor planets with less common orbits. The observational material is CCD frames taken with the Palomar 1.5 m telescope. Positions of 10 comets and 16 different asteroids were published on the Minor Planet Circulars.

Williams, J. G.; Gibson, J.

1987-01-01

404

Familial malignant melanoma  

SciTech Connect

Characteristics associated with familial compared with nonfamilial malignant melanoma were assessed. These data were obtained from consecutive prospectively completed questionnaires on 1169 cases of cutaneous malignant melanoma. Of these, 69 patients indicated a positive family history for this cancer. Among the various clinical and histological variables compared, those that significantly correlated with the familial occurrence of malignant melanoma include younger age at first diagnosis, smaller diameter of the lesion, lower Clark level, decreased frequency of nonmelanoma skin cancer, and reduced prevalence of noncutaneous cancer. Increased awareness of malignant melanoma among family members could account for some of these observations. Identification of the familial variety of malignant melanoma has practical implications concerning early detection and prompt intervention.

Kopf, A.W.; Hellman, L.J.; Rogers, G.S.; Gross, D.F.; Rigel, D.S.; Friedman, R.J.; Levenstein, M.; Brown, J.; Golomb, F.M.; Roses, D.F.; Gumport, S.L.

1986-10-10

405

[Strengthening family planning management].  

PubMed

Prior to 1984, enforcement of family planning policies in an undisclosed PLA military settlement in China's Jinan Military Region was totally inadequate. After notification from the central government, this military settlement immediately began enforcing family planning policies, resulting in sudden and full compliance with the central government's family planning policies. The system of scientific management of promoting and enforcing family planning, established by local administrators, is described. Management by objectives, clearly defined individual tasks and responsibilities, an full cooperation and support on the part of the authorities are some of the factors responsible for the effectiveness and success of the family planning efforts in this military settlement. A number of potential problem areas are identified scientific management techniques in dealing with uncooperative parties are emphasized. PMID:12159410

Hong, C; Shi, Z

1985-09-29

406

The potential impact of family history of metabolic syndrome and risk of type 2 diabetes mellitus: In a highly endogamous population  

PubMed Central

Aim: This study aims to determine the potential impact of positive family history of Metabolic Syndrome (MetS) among two generations, on developing Type 2 Diabetes Mellitus (T2DM) and the potential relation of consanguineous marriage among patients with MetS to the risk of developing T2DM among a sample of Qataris. Design: A cross-sectional study. Setting: Primary healthcare (PHC) centers. Materials and Methods: The survey and measurement were conducted from April 2011 to December 2012 among Qatari nationals above 20 years of age. Of the 2,182 subjects, who were approached to participate in the study, 1,552 (71%) gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by anthropometric measurements and laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III) as well as International Diabetes Federation (IDF). Results: Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9% according to IDF (P < 0.0001). The mean age of MetS patients with T2DM was significantly higher than those without T2DM (Mean 48 ± 9.9 vs. 42.5 ± 9.2; P < 0.001). The proportion of females was higher among MetS patients with T2DM as compared to those without T2DM (61% vs. 51%; P = 0.053). In addition, there were significant differences between MetS patients with and without DM in terms of co-morbidities of hypertension, coronary heart disease, and high cholesterol. The proportion of MetS patients with positive family history for MetS was significantly higher in MetS patients with T2DM as compared to those without T2DM (46.7% vs. 33.8%; P = 0.009). The proportion of positive family history of MetS among fathers (35% vs. 21.9%; P = 0.005), mothers (30.5% vs. 18.8%; P = 0.008), maternal aunt (18.3% vs. 11.2%; P = 0.055), and maternal grand father (19.5% vs. 10%; P = 0.010) were significantly higher in MetS patients with T2DM as compared to the counterpart. The proportion of consanguineous marriages was almost two times higher among MetS patients with T2DM as compared to those without T2DM (80.9% vs. 41.9%; P < 0.001). The proportion of MetS patients with T2DM was lower than MetS patients without DM below 45 years, but after 45 years, the proportion of MetS patients with T2DM remained higher than their counterparts. Conclusion: Family history of MetS among parents, maternal aunt, maternal grandfather, and consanguineous marriages among patients of MetS are significantly associated with the development of T2DM in Qatar. These results support the necessity of earlier screening for T2DM among MetS patients with positive family history of MetS. PMID:24741517

Bener, Abdulbari; Darwish, Sarah; Al-Hamaq, Abdulla O. A.; Yousafzai, Mohammad T.; Nasralla, Eman A.

2014-01-01

407

Small Family, Smart Family? Family Size and the IQ Scores of Young Men. NBER Working Paper No. 13336  

ERIC Educational Resources Information Center

How do families influence the ability of children? Cognitive skills have been shown to be a strong predictor of educational attainment and future labor market success; as a result, understanding the determinants of cognitive skills can lead to a better understanding of children's long run outcomes. This paper uses a large dataset on the male…

Black, Sandra E.; Devereux, Paul J.; Salvanes, Kjell G.

2007-01-01

408

Families First: Keys to Successful Family Functioning An Introduction  

E-print Network

unit. Unlike any other social group, families are able to provide the close emotional support needed to produce self-confident and well-adjusted children and adults. Likewise, families that function age children; the family with teenagers; the family/ launching center; the family/middle years

Liskiewicz, Maciej

409

Engaging Families in In-Home Family Intervention  

ERIC Educational Resources Information Center

Boys Town has created a program called In-Home Family Services to deliver help to families in stress. In-home family intervention programs have become widely used to help more families who are at risk and experiencing difficulties with a wide range of problems including domestic violence, child behavior problems, parent-child and family

Thompson, Ronald W.; Koley, Sarah

2014-01-01

410

RESEARCH ARTICLE Open Access A novel locus (CORD12) for autosomal  

E-print Network

- somal dominant (ad) CRD, six (ABCA4, RPGRIP1, RAX2, CORD8, ADAM9 and CERKL) in autosomal recessive (arRESEARCH ARTICLE Open Access A novel locus (CORD12) for autosomal dominant cone-rod dystrophy for these diseases, we have studied one large non consanguineous French family with autosomal dominant (ad) CRD

Paris-Sud XI, Université de

411

A novel mutation in the thyrotropin (TSH) receptor gene causing loss of TSH binding but constitutive receptor activation in a family with resistance to TSH.  

PubMed

Resistance to TSH is a syndrome due to reduced responsiveness of the thyroid gland to biologically active TSH. Inactivating mutations of the TSH receptor (TSH-R) have been detected in several cases of resistance to TSH, both partial and complete, sporadic and familial. In this study, we describe a family with the presence of resistance to TSH responsible for euthyroid hyperthyrotropinemia in two siblings from consanguineous parents. By direct sequencing of the TSH receptor gene, we identified a new mutation responsible for the substitution of an arginine with a cysteine at position 310, in the extracellular domain of the TSH-R. The mutation was homozygous in two brothers; heterozygous in both parents, an uncle, and an unaffected brother; and absent in the other unaffected brother. When stably transfected in Chinese hamster ovary cells, the Cys310 mutant TSH-R showed loss of response to TSH in terms of cAMP stimulation. However, a constitutive activity in terms of basal cAMP production was detected in the Cys310 mutant, compared with the wild-type TSH-R. Our data suggest that such a Cys310 TSH-R mutant may determine both the TSH resistance and the clinical euthyroidism detected in this family. PMID:11095460

Russo, D; Betterle, C; Arturi, F; Chiefari, E; Girelli, M E; Filetti, S

2000-11-01

412

Targeted next-generation sequencing identifies a homozygous nonsense mutation in ABHD12, the gene underlying PHARC, in a family clinically diagnosed with Usher syndrome type 3  

PubMed Central

Background Usher syndrome (USH) is an autosomal recessive genetically heterogeneous disorder with congenital sensorineural hearing impairment and retinitis pigmentosa (RP). We have identified a consanguineous Lebanese family with two affected members displaying progressive hearing loss, RP and cataracts, therefore clinically diagnosed as USH type 3 (USH3). Our study was aimed at the identification of the causative mutation in this USH3-like family. Methods Candidate loci were identified using genomewide SNP-array-based homozygosity mapping followed by targeted enrichment and next-generation sequencing. Results Using a capture array targeting the three identified homozygosity-by-descent regions on chromosomes 1q43-q44, 20p13-p12.2 and 20p11.23-q12, we identified a homozygous nonsense mutation, p.Arg65X, in ABHD12 segregating with the phenotype. Conclusion Mutations of ABHD12, an enzyme hydrolyzing an endocannabinoid lipid transmitter, cause PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and early-onset cataract). After the identification of the ABHD12 mutation in this family, one patient underwent neurological examination which revealed ataxia, but no polyneuropathy. ABHD12 is not known to be related to the USH protein interactome. The phenotype of our patient represents a variant of PHARC, an entity that should be taken into account as differential diagnosis for USH3. Our study demonstrates the potential of comprehensive genetic analysis for improving the clinical diagnosis. PMID:22938382

2012-01-01

413

Family intervention for schizophrenia  

PubMed Central

Background People with schizophrenia from families that express high levels of criticism, hostility, or over involvement, have more frequent relapses than people with similar problems from families that tend to be less expressive of emotions. Forms of psychosocial intervention, designed to reduce these levels of expressed emotions within families, are now widely used. Objectives To estimate the effects of family psychosocial interventions in community settings for people with schizophrenia or schizophrenia-like conditions compared with standard care. Search strategy We updated previous searches by searching the Cochrane Schizophrenia Group Trials Register (September 2008). Selection criteria We selected randomised or quasi-randomised studies focusing primarily on families of people with schizophrenia or schizoaffective disorder that compared community-orientated family-based psychosocial intervention with standard care. Data collection and analysis We independently extracted data and calculated fixed-effect relative risk (RR), the 95% confidence intervals (CI) for binary data, and, where appropriate, the number needed to treat (NNT) on an intention-to-treat basis. For continuous data, we calculated mean differences (MD). Main results This 2009-10 update adds 21 additional studies, with a total of 53 randomised controlled trials included. Family intervention may decrease the frequency of relapse (n = 2981, 32 RCTs, RR 0.55 CI 0.5 to 0.6, NNT 7 CI 6 to 8), although some small but negative studies might not have been identified by the search. Family intervention may also reduce hospital admission (n = 481, 8 RCTs, RR 0.78 CI 0.6 to 1.0, NNT 8 CI 6 to 13) and encourage compliance with medication (n = 695, 10 RCTs, RR 0.60 CI 0.5 to 0.7, NNT 6 CI 5 to 9) but it does not obviously affect the tendency of individuals/families to leave care (n = 733, 10 RCTs, RR 0.74 CI 0.5 to 1.0). Family intervention also seems to improve general social impairment and the levels of expressed emotion within the family. We did not find data to suggest that family intervention either prevents or promotes suicide. Authors’ conclusions Family intervention may reduce the number of relapse events and hospitalisations and would therefore be of interest to people with schizophrenia, clinicians and policy makers. However, the treatment effects of these trials may be overestimated due to the poor methodological quality. Further data from trials that describe the methods of randomisation, test the blindness of the study evaluators, and implement the CONSORT guidelines would enable greater confidence in these findings. PMID:21154340

Pharoah, Fiona; Mari, Jair; Rathbone, John; Wong, Winson

2014-01-01

414

Cultural adaptations of evidence-based family interventions to strengthen families and improve children's developmental outcomes  

Microsoft Academic Search

Evidence-based parenting and family interventions are effective in improving parenting skills, positive parent–child relations and children's developmental outcomes. Programmes based on “principles of effective prevention” do not prove that a programme works. Evidence-based programmes (EBPs) are programmes tested in multiple randomized control trials by different researchers and producing large effect sizes. Hence, selecting a family EBP that best matches the

Karol L. Kumpfer; Cátia Magalhães; Jing Xie

2012-01-01

415

[Sexuality, discussion and family planning].  

PubMed

Choosing a contraceptive forces clients to reflect on their way of viewing sexual relations and to confront norms and taboos they have internalized. This situation is charged with emotion which largely goes beyond technical and medical aspects. The Interregional Center of Family Planning in Monthey in the Chablais region of Switzerland has developed a framework to manage implicit demands from family planning clients. This framework permits counselors to hear the here-and-now of the client and her request and to link the request with the before-and-after. After learning the most pressing reason for visiting the clinic, the counselor begins prevention work: to expose the wishes of the client and to encourage self-confidence to dare to say no. The framework to use in a session with an adolescent guides the counselor to consider the following: the relationship with her parents; loyalty towards the original culture of her parents; success or failure at school or at her apprenticeship; her relationship with the person with whom she had sex; body image; experience of the first in-love emotions or first sexual intercourse; sense of control at the gynecologist office; and, for older teens (18-20 years), her professional life plan and becoming self-reliant. The framework to use in a session with a postpartum woman guides the counselor to consider the following: childbirth experience; relationship with the baby and evolution of the mother-baby bond; capacity of the couple to adapt to changes; return to home; role of the family and family-in-law; and how everyone envisions his/her role and place. The framework to use in a session with a woman who has undergone induced abortion guides the counselor to consider the following: eventual prejudices linked to the contraceptive (e.g., fear of cancer); her feelings about failure of that contraceptive; self-image as a woman; relationship with her partner; desire for children; and couple's plan. PMID:7847923

Launaz, E

1994-01-01

416

Rare large homozygous CFTR gene deletion in an Iranian patient with cystic fibrosis.  

PubMed

Cystic fibrosis, a common autosomal recessive genetic disorder among Caucasians, is caused by defects in the transmembrane conductance regulatory (CFTR) gene. The analysis of CFTR gene mutations is useful to better characterize the disease, and for preconceptional screening, prenatal and preimplantation genetic diagnosis. Here we report the results of a genetic analysis in a 16-year-old boy from southwestern Iran diagnosed as having cystic fibrosis in infancy based on gastrointestinal and pulmonary manifestations, with positive sweat chloride tests. He lacked both normal and mutant forms of the fragment corresponding to the ?F508 allele in initial genetic studies. Multiplex ligation-dependent probe amplification-based testing revealed a homozygous deletion spanning exons 4 to 10 of the CFTR gene. We predict an in-frame deletion removing 373 amino acids based on our sequencing results. Determining CFTR gene mutations in patients and their family members would be helpful to prevent the occurrence of new cases, especially in populations in which consanguinity is common. PMID:25133155

Farjadian, Shirin; Moghtaderi, Mozhgan; Zuntini, Roberta; Ferrari, Simona

2014-08-16

417

Trauma Therapy for Death Row Families  

Microsoft Academic Search

The family members of death row inmates undergo unique suffering that includes disenfranchised grief and intense psychological trauma. In Texas, where executions occur at a rate of one every two weeks, this class of trauma victims presumably is large: a fact that should generate public mental health concern. Yet, the class remains virtually unknown to the therapeutic community. Very little

Walter C. Long

2011-01-01

418

The inward rectifier potassium channel family  

Microsoft Academic Search

Recent cloning of a family of genes encoding inwardly rectifying K+ channels has provided the opportunity to explain some venerable problems in membrane biology. An expanding number of novel inwardly rectifying K+ channel clones has revealed multiple channel subfamilies that have specialized roles in cell function. The molecular determinants of inward rectification have been largely elucidated with the discovery of

Craig A Doupnik; Norman Davidson; Henry A Lester

1995-01-01

419

Intra-family succession in Italian farms  

Microsoft Academic Search

The succession in family farm is a critical issue: it not only involves the transmission of wealth, but also of specific skills and of specific farm management techniques. Since a large share of farmers in Italy are old, the lack of prospective successors in their farms would imply that a change in the farm management will take place. In some

Alessandro Corsi

2004-01-01

420

Social Background Differences in Early Family Behavior  

ERIC Educational Resources Information Center

Social background has historically been recognized as a major factor influencing family behavior, though recent work has largely emphasized racial/ethnic influences. Here we use 1994 - 1995 and 2001 - 2002 Add Health data to examine the cohabitation, first marriage, and first birth experience of young women. In a multi state life table context,…

Schoen, Robert; Landale, Nancy S.; Daniels, Kimberly; Cheng, Yen-Hsin Alice

2009-01-01

421

Overworked Faculty: Job Stresses and Family Demands  

Microsoft Academic Search

Do professors put in very long workweeks solely out of a love of their work, or do expectations for teaching and publishing essentially require a sixty-hour workweek for the successful completion of the job? How do faculty members reconcile the demands of an academic career with the realities of family life? Drawing on a large national survey of postsecondary faculty

Jerry A. Jacobs; Sarah E. Winslow

2004-01-01

422

Structure and function of the human Poly(ADP-ribose) polymerase enzyme family  

E-print Network

The poly(ADP-ribose) polymerase (PARP) family of enzymes in humans is comprised of 17 proteins. PARP-1, the first member of the family, synthesizes a large, complex post-translational modification, poly(ADP-ribose). While ...

Rood, Jennifer E. (Jennifer Evelyn)

2013-01-01

423

Partners in family planning.  

PubMed

Studies of the Africa OR/TA Project and other Cooperating Agencies suggest that support of family planning by traditional health practitioners (THPs), traditional birth attendants (TBAs), Islamic religious leaders, and male opinion leaders (MOLs) can result in an increase in the availability of family planning services in the community. A study in Kenya shows that 100 trained THPs who were actively involved in family planning (i.e., distributors of condoms, oral contraceptives, and primary health care drugs) increased contraceptive use in Siaya and Kakamega districts from 7% to 15% and from 14% to 34%, respectively. Contraceptive use did not change in the 2 control areas. Two years after TBAs underwent training in family planning promotion, the proportion of women who named TBAs as their source of family planning information increased from 2% to 18%. In The Gambia, integration of Islamic religious leaders into family planning promotion activities resulted in an increase of current modern contraceptive method use from 9% to 20% for males and from 9% to 26% for females. Involvement of 69 MOLs has increased knowledge of family planning methods in Nkambe, Cameroon. For example, among males, knowledge about the condom increased from 52% to 81% and knowledge about spermicides increased from 12% to 44%. The corresponding figures for women were 47% to 72% and 17% to 42%, respectively. PMID:12319039

1994-12-01

424

Families Get Involved! Learning Partners.  

ERIC Educational Resources Information Center

Noting that families who are involved in their children's education make a difference in their child's performance, this two-page information sheet encourages families to get involved by listing the benefits of family involvement on one side and the ways adult family members can help in the school on the other. As a result of family participation:…

Office of Educational Research and Improvement (ED), Washington, DC. Media and Information Services.

425

Canadian Families (Les Familles Canadiennes).  

ERIC Educational Resources Information Center

Structural changes that have taken place in Canadian families in recent decades are described in this booklet. Topical sections are as follows: (1) What Counts in Canadian Families (importance of (importance of family); (2) The Family--Variations on a Theme origins, family structure, seniors aged 60 and over, how lives are spent, religion); (3)…

Vanier Inst. of the Family, Ottawa (Ontario).

426

THE SCHOOL OF FAMILY LIFE  

E-print Network

- ment, clothing and textiles, early childhood education, family and consumer science education, familyTHE SCHOOL OF FAMILY LIFE ALUMNI MAGAZINE SPRING 2011 FAMILY CONNECTIONS CO-PLAY: THE LATEST VIDEO economics education, clothing and textiles, interior design, or family and consumer sciences (FACS

Martinez, Tony R.

427

Family Day Care Training Curriculum.  

ERIC Educational Resources Information Center

California's Family Day Care Training Program was designed to recruit and train in 7 weeks, Lao, Vietnamese, and Chinese refugees to establish their own state-licensed, family day care homes. Topics in the program's curriculum include an introduction to family day care, state licenses for family day care, state licensing requirements for family

Nakatsu, Gail

428

Child And Family Studies Department Of Child And Family Studies  

E-print Network

, psychology, medicine, family law, counseling, health care, child and family studies and education. GRADUATE, mental health, health and juvenile justice agencies, youth programs, schools and parent and family and advanced degrees in counseling psychology, developmental psychology, educational psychology, sociology

Raina, Ramesh

429

Effects of family routines and family stress on child competencies  

E-print Network

Assessment...........................................................................................23 Parental Monitoring and Family Structure...............................................................24 Ego Control... and Family Structure Rotated Component Matrix...................27 4 Confirmatory Factor Analysis Results for the Ego Control Scale ............................29 5 Confirmatory Factor Analysis Results for the Family Status Scale...

Hill, Crystal Renee

2006-10-30

430

Family History Assessment  

PubMed Central

Background Family Healthware™, a tool developed by the CDC, is a self-administered web-based family history tool that assesses familial risk for six diseases (coronary heart disease, stroke, diabetes, and colon, breast and ovarian cancers) and provides personalized prevention messages based on risk. The Family Healthware Impact Trial (FHITr) set out to examine the clinical utility of presenting personalized preventive messages tailored to family history risk for improving health behaviors. Purpose The purpose of this study was to examine the impact of Family Healthware on modifying disease risk perceptions, particularly among those who initially underestimated their risk for certain diseases. Design A total of 3786 patients were enrolled in a cluster-randomized trial to evaluate the clinical utility of Family Healthware. Setting/participants Participants were recruited from 41 primary care practices among 13 states between 2005 and 2007. Main outcome measures Perceived risk for each disease was assessed at baseline and 6-month follow-up using a single-item comparative risk question. Analyses were completed in March 2012. Results Compared to controls, Family Healthware increased risk perceptions among those who underestimated their risk for heart disease (15% vs 9%, p<0.005); stroke (11% vs 8%, p<0.05); diabetes (18% vs 11%, p<0.05); and colon cancer (17% vs 10%, p=0.05); but not breast or ovarian cancers. The majority of underestimators did not shift in their disease risk perceptions. Conclusions Family Healthware was effective at increasing disease risk perceptions, particularly for metabolic conditions, among those who underestimated their risk. Results from this study also demonstrate the relatively resistant nature of risk perceptions. Trial registration This study is registered at clinicaltrials.gov NCT00164658. PMID:22992357

Wang, Catharine; Sen, Ananda; Ruffin, Mack T.; Nease, Donald E.; Gramling, Robert; Acheson, Louise S.; O'Neill, Suzanne M.; Rubinstein, Wendy S.

2012-01-01

431

The Case of the Missing Ceres Family  

NASA Astrophysics Data System (ADS)

Most of the largest asteroids in the main belt are associated with an impact-generated dynamical family. The Vesta family dominates the inner asteroid belt with its numbers, and was a critical piece of evidence in tying the HED meteorites to Vesta. In addition to Vesta (the third-largest asteroid), Pallas (the second-largest asteroid), Hygiea (the fourth-largest asteroid), and the largest S-class asteroid, 15 Eunomia, all have dynamical families. It is curious that the very largest body in the asteroid belt, Ceres, is missing from this list of parents. The most recent dynamical family studies show Ceres to be unassociated with a family of any size. This alone is perhaps not sufficient to draw any conclusion, but motivates us towards the considerations we make here. We use relevant published works to demonstrate that Ceres’ collisional history very likely includes large enough impacts to create a family, that a Ceres family would be found if extant, and that a Ceres family would not be easily erased once created if it is like the rocky bodies comprising “typical” asteroid families. There is observational and model evidence that Ceres is a differentiated body, with an icy mantle atop a rocky core. However, the surface of Ceres is too warm to maintain ice for significantly long periods of time (save very near the poles), and the retreat of ice does not effectively halt until it reaches a depth of rough order 100-1000 m (depending upon latitude and surface temperature) beneath an insulating lag deposit. What if a family-forming impact primarily or solely liberated icy material from the postulated icy mantle? To first order, an icy Ceres family is subject to the same sublimation rates as Ceres itself. Can its members have simply sublimed away? An order-of-magnitude argument shows that sublimation may have been a powerful force in erasing an icy Ceres family, this simplified model very likely understates the case for sublimation. We will show that the lack of a family has implications for Ceres’ internal structure, and further hope to encourage research beyond the scope of this work – geodynamical, chemical and collisional modeling – that can provide additional firm constraints.

Rivkin, Andrew S.; Asphaug, Erik; Bottke, William F.

2014-11-01

432

Wujiang's service-oriented family planning programme.  

PubMed

Wujiang City in south Jiangsu Province is a county-level city, well known for its economic development and effective family planning program. Family planning is practiced voluntarily by the people. The growth rate of the city's population has decreased to 5.47/1000; the proportion of planned births has increased to 98%; and the total fertility rate has declined to 1.5. There are 34 towns (and townships) and 883 administrative villages under the jurisdiction of the city. The living standard has improved significantly. The successful implementation of family planning is largely due to the quality services delivered to farmers, especially women of reproductive age. In an interview, Mme. Ji and Mme. Shen, chiefs of the Wujiang Family Planning Committee, describe the services they deliver. The information, education, and communication (IEC) program is focused on population schools (city, town, township, and village), which deliver information to middle school students, premarital youth, and women who are