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.
Institute for Human Genetics, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
O
O
Bartsch
A
A
Vatter
U
U
Zechner
N
N
Kohlschmidt
C
C
Wetzig
A
A
Baumgart
S
S
Nospes
T
T
Haaf
Annerose
A
Keilmann
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