Lack of association between Connexin 31 (GJB3) alterations and sensorineural deafness in Austria.
Mutations in the gap junction protein beta 3 (GJB3) gene encoding Connexin 31 (Cx31) are known to cause autosomal inherited sensorineural deafness, erythrokeratodermia and neuropathy. The role of Cx31 mutations has not been described in familial cases of non-syndromic hearing impairment (NSHI) in central European populations. To identify mutations in the Austrian population, highly selected familial (n=24) and sporadic (n=21) cases of isolated NSHI were screened by analysis of the complete coding sequence of Cx31, after exclusion of a common Cx26 causing deafness. Three different variations occurring in a total of 37% of all cases were identified. A C94T (R32W) missense mutation was seen in 4.4% of cases and two silent alterations C357T and C798T were detected in 8.9% and 24.4% of cases exclusively in a heterozygous pattern. No correlation between Cx31 alterations and deafness was found. To investigate the role of heterozygous Cx31 variations for a possibly combination allelic disease inheritance with Cx26 mutations as shown for Connexin 30 and Connexin 26, patients with Cx26 variations were tested. Our data suggest that Cx31 alterations are common but have no or a low genetic relevance in the Austrian hearing impaired population with or without Cx26 alterations.
Frei
Klemens
K
Department of Otorhinolaryngology, University Hospital of Vienna, University of Vienna, AKH-8J Waehringer, Gürtel 18-20, Vienna A-1090, Austria. klemens.frei@akh-wien.ac.at
Ramsebner
Reinhard
R
Hamader
Gertrude
G
Lucas
Trevor
T
Schoefer
Christian
C
Baumgartner
Wolf-Dieter
WD
Wachtler
Franz J
FJ
Kirschhofer
Karin
K
D001317:Austria; D025063:Chromosome Disorders / Q000235:genetics*; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005820:Genetic Testing; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26; C068044:GJB3 protein, human