TY - JOUR
T1 - Molecular genetics of hearing impairment due to mutations in gap junction genes encoding beta connexins
AU - Rabionet, Raquel
AU - Gasparini, Paolo
AU - Estivill, Xavier
PY - 2000
Y1 - 2000
N2 - 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, GSB2, GSB3, and GSB6, 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; GSB3 erythrokeratodermia variabilis; and GSB1, peripheral neuropathy), and non-syndromic (GJB2, GSB3, and GSB6). Among these genes, mutations in GSB2 account for about 50% of all congenital cases of hearing impairment. Three mutations in GSB2 (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 GSB2 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 GSB2 in some populations provides the tools for molecular diagnosis, carrier detection, and prenatal diagnosis of congenital hearing impairment. (C) 2000 Wiley-Liss, Inc.
AB - 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, GSB2, GSB3, and GSB6, 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; GSB3 erythrokeratodermia variabilis; and GSB1, peripheral neuropathy), and non-syndromic (GJB2, GSB3, and GSB6). Among these genes, mutations in GSB2 account for about 50% of all congenital cases of hearing impairment. Three mutations in GSB2 (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 GSB2 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 GSB2 in some populations provides the tools for molecular diagnosis, carrier detection, and prenatal diagnosis of congenital hearing impairment. (C) 2000 Wiley-Liss, Inc.
KW - CMTX1
KW - Connexin, beta
KW - Deafness
KW - DF NA2
KW - DFNA3
KW - DFNB1
KW - Erythrokeratodermia
KW - Gap junction protein
KW - GJB1
KW - GJB2
KW - GJB3
KW - GJB6
KW - Hearing impairment, non-syndromic
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UR - http://www.scopus.com/inward/citedby.url?scp=0033850250&partnerID=8YFLogxK
U2 - 10.1002/1098-1004(200009)16:3<190::AID-HUMU2>3.0.CO;2-I
DO - 10.1002/1098-1004(200009)16:3<190::AID-HUMU2>3.0.CO;2-I
M3 - Article
C2 - 10980526
AN - SCOPUS:0033850250
VL - 16
SP - 190
EP - 202
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 3
ER -