Homozygous R127H Mutation in the GJB2 Gene in a Boy with Initial Unilateral Severe Hearing Loss

Introduction

Congenital sensorineural hearing loss (SNHL) has an incidence in children of 1–2 per 1 000 for bilateral severe-to-profound losses (>50 dB) and up to 4 per 1 000 if mild-to-moderate and unilateral losses are included. Single gene defects account for half of the cases of childhood hearing impairment. To date, more than 70 gene loci have been reported to be involved in non-syndromic forms of deafness. In addition, more than 400 syndromes with impaired hearing are known [Thönnissen E et al., Hum Genet 2002; 111: 190–197).

The Connexins (Cx) form a family of transmembrane proteins consisting of 20 members in the human genome (Denoyelle F et al., Lancet 1999; 353: 1298–1303). Mutations in the connexin26 (Cx26) gene (GJB2) account for about 50% of inherited cases of non-syndromic deafness (DFNB1). More than 90 different mutations of the Cx26 gene have been described so far. The most common mutation (70% of cases) is a recessive nonsense mutation (35delG) resulting in a premature stop of translation (Zelante et al. 1997; Hum Mol Genet 1997; 6: 1605–1609).

Uni- or bilateral sensorineural hearing loss (SNHL) can vary from prelingual onset with mild to complete hearing loss to hearing impairment with late onset. A correlation between the position or type of mutation and the severeness of deafness can be shown in some cases (genotype-phenotype correlation) (Denoyelle F et al., Lancet 1999; 353: 1298–1303). The functional implications of most mutants and, in some cases, the mode of inheritance are still elusive. This aggravates genetic diagnostic and counselling for patients with hearing impairment, which are offered by many clinics and other facilities in the meantime.

Here, we report on a boy with initial unila­teral severe hearing loss and homozygous mutation of the R127H.