GJB2 mutations and genotype-phenotype correlation in 335 patients from germany with nonsyndromic sensorineural hearing loss: evidence for additional recessive mutations not detected by current methods.
We report on 335 patients (319 families) with mild-to-profound nonsyndromic sensorineural hearing loss. We identified 178 mutated GJB2 alleles representing 29 different sequence changes (including 3 novel mutations: Q7P, N14D, H100Q), and 2 alleles with the deletion del(GJB6-D13S1830) of the GJB6 gene. Eleven GJB2 mutations (119 mutated alleles) were truncating (T), and 18 mutations (59 alleles) were nontruncating (NT). Biallelic GJB2 mutations were found in 71 patients (21.2%; 67 families; 25 different genotypes). Audiograms of 62 patients (56 families) with biallelic GJB2 mutations typically indicated a profound hearing loss with T/T mutations, moderate hearing loss with T/NT mutations, and mild hearing impairment with NT/NT mutations (p < 0.01, Student's t test). From 37 patients (34 families) with biallelic GJB2 mutations, audiograms at different ages were available and indicated progressive hearing loss (>15 dB) in 10 patients (27.0%, 10 families). Interestingly, we identified an unexpectedly large subset of patients (n = 29; 8.7%) presenting with only one GJB2 mutation (n = 14 T/wild-type; n = 15 NT/wild-type). This strongly suggests the presence of additional recessive mutations that are not detected by current GJB2 mutation and GJB6 deletion analyses.
Bartsch
O
O
Institute for Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Vatter
A
A
Zechner
U
U
Kohlschmidt
N
N
Wetzig
C
C
Baumgart
A
A
Nospes
S
S
Haaf
T
T
Keilmann
Annerose
A
D000483:Alleles; D001299:Audiometry; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005808:Genes, Recessive; D056726:Genetic Association Studies; D005838:Genotype; D005858:Germany; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26