Assignment of connexin 26 (GJB2) and 46 (GJA3) genes to human chromosome 13q11→q12 and mouse chromosome 14D1-E1 by in situ hybridization

Mignon, C.; Fromaget, C; Mattéi, Marie Geneviève; Gros, Danièle; Yamasaki, Hideo; Mesnil, Marc

doi:10.1159/000134183

Cited by 31 publications

(14 citation statements)

References 2 publications

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“…Connexin genes are known to be clustered. There are three connexins localized to this region: Cx26, Cx30, and Cx46 (Mignon et al, 1996), two of which (Cx26 and Cx30) are expressed in the cochlea. It is possible that there is another gene in this region that is also expressed in the cochlea, responsible for the non-GJB2, DFNB1 linked hearing loss, perhaps a fourth connexin gene in this cluster.…”

Section: Resultsmentioning

confidence: 99%

Human Connexin 30 (GJB6), a Candidate Gene for Nonsyndromic Hearing Loss: Molecular Cloning, Tissue-Specific Expression, and Assignment to Chromosome 13q12

Kelley

Abe

Askew³

et al. 1999

Genomics

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Section: Resultsmentioning

confidence: 99%

Human Connexin 30 (GJB6), a Candidate Gene for Nonsyndromic Hearing Loss: Molecular Cloning, Tissue-Specific Expression, and Assignment to Chromosome 13q12

Kelley

Abe

Askew³

et al. 1999

Genomics

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“…Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 at the centromeric side and D13S1830 at the telomeric one. This region contains four cloned genes: connexin 26 (Cx 26), connexin 46 (Cx46), 22 α-tubulin TUBA2 23 and zinc finger ZNF198. 24 Cx26 was shown to be abundantly expressed in hair follicles 25 and hence was considered as a good candidate for involvement in HED.…”

Section: Discussionmentioning

confidence: 99%

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping

et al. 2000

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HED is an autosomal dominant skin disorder that is particularly common in the French Canadian population of south-west Quebec. We previously mapped the HED gene to the pericentromeric region of chromosome 13q using linkage analysis in eight French Canadian families. In this study, we extend our genetic analysis to include a multiethnic group of 29 families with 10 polymorphic markers spanning 5.1 cM in the candidate region. Two-point linkage analysis strongly suggests absence of genetic heterogeneity in HED in four families of French, Spanish, African and Malaysian origins. Multipoint linkage analysis in all 29 families generated a peak lod score of 53.5 at D13S1835 with a 1 lod unit support interval spanning 1.8 cM. Recombination mapping placed the HED gene in a 2.4 cM region flanked by D13S1828 proximally and D13S1830 distally. We next show evidence for a strong founder effect in families of French Canadian origin thereby representing the first example of a founder disease in the south-west part of the province of Quebec. Significant association was found between HED in these families and all markers analysed (Fisher's exact test, P < 0.001). Complete allelic association was detected at D13S1828, D13S1827, D13S1835, D13S141 and D13S175 (P excess = 1) spanning 1.3 cM. A major haplotype including all 10 associated alleles was present on 65% of affected chromosomes. This haplotype most likely represents the founder haplotype that introduced the HED mutation into the French Canadian population. Luria-Delbrück equations and multipoint likelihood linkage disequilibrium analysis positioned the gene at the D13S1828 locus (likely range estimate: 1.75 cM) and 0.58 cM telomeric to this marker (support interval: 3.27 cM) respectively.

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“…Since the GJB2 gene was localized on chromosome 13 [Willecke et al, 1990;Mignon et al, 1996] within this interval defined by linkage studies, and previous work showed that cochlea supporting cells are interconnected via gap junctions, which are formed by connexons containing Connexin26 [Kikuchi, 1995], the GJB2 gene was considered a good candidate for DFNB1. A deletion of one G within a stretch of six Gs at positions 30 to 35 of GJB2 (mutation 35delG), causing a frameshift and a premature termination at codon 13, was detected in 63% of the chromosomes linked to chromosome 13.…”

Section: For Deafnessmentioning

confidence: 99%

Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins

Rabionet¹,

Gasparini

Estivill³

2000

Hum. Mutat.

184

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Deafness is a complex disorder that involves a high number of genes and environmental factors. There has been enormous progress in non‐syndromic deafness research during the last five years, with the identification of over 50 loci and 15 genes. Among these, three genes, GJB2, GJB3, and GJB6, encode for connexin proteins (Connexin26, Connexin31, and Connexin30, respectively). Another connexin (Connexin32, encoded by GJB1) is involved in X‐linked peripheral neuropathy and hearing impairment. Mutations in these genes cause autosomal recessive (GJB2 and GJB3), autosomal dominant (GJB2, GJB3, and GJB6) or X‐linked (GJB1) hearing impairment, both syndromic (GJB2, keratoderma; GJB3 erythrokeratodermia variabilis; and GJB1, peripheral neuropathy), and non‐syndromic (GJB2, GJB3, and GJB6). Among these genes, mutations in GJB2 account for about 50% of all congenital cases of hearing impairment. Three mutations in GJB2 (35delG, 167delT, and 235delC) are particularly common in specific populations (Caucasoid, Jewish Ashkenazi, and Oriental, respectively), leading to carrier frequencies between one in 30 and one in 75. Over 50 mutations have been identified in the GJB2 gene, of which some missense changes (M34T, W44C, G59A, D66H, and R75W) have a negative dominant action in hearing impairment, with partial to full penetrance. Functional studies for some missense mutations in connexins 26, 30, and 32 have indicated abnormal gap junction conductivity. Expression patterns in mouse and rat cochlea indicate that Connexin26 and Connexin30 are expressed in the supportive cells of the cochlea, suggesting a potential role in endolymph potassium recycling. The high prevalence of mutations in GJB2 in some populations provides the tools for molecular diagnosis, carrier detection, and prenatal diagnosis of congenital hearing impairment. Hum Mutat 16:190–202, 2000. © 2000 Wiley‐Liss, Inc.

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Assignment of connexin 26 (GJB2) and 46 (GJA3) genes to human chromosome 13q11→q12 and mouse chromosome 14D1-E1 by in situ hybridization

Cited by 31 publications

References 2 publications

Human Connexin 30 (GJB6), a Candidate Gene for Nonsyndromic Hearing Loss: Molecular Cloning, Tissue-Specific Expression, and Assignment to Chromosome 13q12

Human Connexin 30 (GJB6), a Candidate Gene for Nonsyndromic Hearing Loss: Molecular Cloning, Tissue-Specific Expression, and Assignment to Chromosome 13q12

Clouston hidrotic ectodermal dysplasia (HED): genetic homogeneity, presence of a founder effect in the French Canadian population and fine genetic mapping

Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins

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