Despite the identification of mutations in the connexin 26 (GJB2) gene as the most common cause of recessive nonsyndromic hearing loss, the pattern of hearing impairment with these mutations remains inconsistent. Recently a deletion encompassing the GJB6 gene was identified and hypothesized to also contribute to hearing loss. We hereby describe the hearing impairment in Dutch patients with biallelic connexin 26 (GJB2) and GJB2 + connexin 30 (GJB6) mutations. The audiograms of patients who were screened for GJB2 and GJB6 mutations were analysed retrospectively. Standard statistical testing was done for symmetry and shape, while repeated measurement analysis was used to assess the relation between mutation and severity. Progression was also studied via linear regression analysis. Of 222 hearing-impaired individuals, 35 exhibited sequence variations; of these 19 had audiograms for study. Hearing loss in patients with biallelic "radical" (i.e. deletions, nonsense and splice site) mutations was significantly worse than in the wild type and heterozygotes (SAS proc GENMOD, p = 0.013). The presence of at least one missense mutation in compound heterozygotes tends to lead to better hearing thresholds compared to biallelic radical mutations (p = 0.08). One patient with the [35delG] + [del(GJB6-D13S1830)] genotype was severely impaired. Non-progressive hearing impairment was demonstrated in five 35delG homozygotes in individual longitudinal analyses. However a patient with the [299A > C] + [416G > A] genotype showed significant threshold progression in the lower frequencies. Findings on asymmetry and shape were inconclusive. Our data support the hypothesis that severity is a function of genotype and its effect on the amino acid sequence. A bigger cohort is required to establish non-progressivity more definitively.

Connexin 26 (CX26), Connexin 30 (CX30), Gap junction beta-2 (GJB2), Gap junction beta-6 (GJB6), Hearing impairment, hearing loss
dx.doi.org/10.1016/j.ijporl.2004.08.015, hdl.handle.net/1765/67584
International Journal of Pediatric Otorhinolaryngology
Erasmus MC: University Medical Center Rotterdam

Santos, R.L.P, Cremers, C.W.R.J, Aulchenko, Y.S, Huygen, P.L.M, van der Donk, K.P, de Wijs, I.J, … Hoefsloot, E.H. (2005). Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutations. International Journal of Pediatric Otorhinolaryngology, 69(2), 165–174. doi:10.1016/j.ijporl.2004.08.015