Audiological features of GJB2 (connexin 26) deafness.
OBJECTIVE
The aim of the present study was to characterize audiological profiles in patients with GJB2 deafness


METHODS
We screened DNA from 399 individuals with nonsyndromic deafness for mutations in the connexin 26 gene (GJB2) by sequence analysis. A total of 77 (19%) of these deaf individuals were biallelic GJB2 mutations (either homozygous or compound heterozygous mutations) (GJB2 deafness). Using the audiological classification criteria of genetic deafness proposed by the European Workshop on Genetic Hearing Loss, we analyzed audiograms of these patients to characterize audiological features of the GJB2 deafness. In addition, we reviewed audiological data of 411 deafness cases from the literature providing details of audiological data (including 157 with GJB2 deafness).


RESULTS
All categories of hearing loss severity were found, with significant differences in the findings from GJB2 cases: 1 (4.5%) of 22 individuals with mild hearing loss, 10 (13.3%) of 75 with moderate loss, 14 (14.9%) of 94 with severe loss, and 52 (25%) of 208 with profound deafness (Chi-square test, 3 df, p = 0.016). 81.6% of patients with GJB2 mutations had severe to profound loss, 18.4% with mild to moderate loss (Chi-square test, p = 0.014). The 235delC mutation was always associated with profound deafness. The main audiogram shapes found were residual/sloping (72.7%) and flat (23.4%). There were no differences in the severity and audiogram shapes of the hearing impairment between homozygous and compound heterozygous GJB2 deafness (Chi-square test, p > 0.05).


CONCLUSIONS
Our study shows that the probability of finding biallelic GJB2 mutations increases with the severity of hearing loss. Audiograms associated with GJB2 deafness were usually nonspecific. Patients with unknown causes of severe or profound hearing loss should be routinely tested for GJB2 mutations, but due to the variability in hearing loss, individuals with lesser degrees of hearing loss should not be precluded from testing.
Liu
Xue Zhong
XZ
Department of Otolaryngology, University of Miami, Miami, Florida 33136, USA.
Pandya
Arti
A
Angeli
Simon
S
Telischi
Fred F
FF
Arnos
Kathleen S
KS
Nance
Walter E
WE
Balkany
Thomas
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D001301:Audiometry, Pure-Tone; D001309:Auditory Threshold / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics*; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D017421:Sequence Analysis / Q000379:methods; D012720:Severity of Illness Index
D017630:Connexins; C000607042:GJB2 protein, human; D000072259:Connexin 26