GJB2 (connexin 26) gene mutations in Moroccan patients with autosomal recessive non-syndromic hearing loss and carrier frequency of the common GJB2-35delG mutation

Int J Pediatr Otorhinolaryngol. 2007 Aug;71(8):1239-45. doi: 10.1016/j.ijporl.2007.04.019. Epub 2007 Jun 5.

Abstract

Objective: Mutations in the connexin 26 gene (GJB2), which encodes a gap-junction protein expressed in the inner ear, have been shown to be responsible for a major part of autosomal recessive non-syndromic hearing loss in Caucasians. The aim of our study was to determine the prevalence and spectrum of GJB2 mutations, including the (GJB6-D13S1830) deletion, in Moroccan patients and estimate the carrier frequency of the 35delG mutation in the general population.

Methods: Genomic DNA was isolated from 81 unrelated Moroccan familial cases with moderate to profound autosomal recessive non-syndromic hearing loss and 113 Moroccan control individuals. Molecular studies were performed using PCR-Mediated Site Directed Mutagenesis assay, PCR and direct sequencing to screen for GJB2, 35delG and del(GJB6-D13S1830) mutations.

Results: GJB2 mutations were found in 43.20% of the deaf patients. Among these patients 35.80% were 35delG/35delG homozygous, 2.47% were 35delG/wt heterozygous, 3.70% were V37I/wt heterozygous, and 1 patient was E47X/35delG compound heterozygous. None of the patients with one or no GJB2 mutation displayed the common (GJB6-D13S1830) deletion. We found also that the carrier frequency of GJB2-35delG in the normal Moroccan population is 2.65%.

Conclusions: These findings indicate that the GJB2-35delG mutation is the major cause of autosomal recessive non-syndromic hearing loss in Moroccan population. Two other mutations were also detected (V37I and E47X), in agreement with similar studies in other populations showing heterogeneity in the frequencies and types of mutation in connexin 26 gene.

MeSH terms

  • Chromosome Mapping
  • Connexin 26
  • Connexins / genetics*
  • DNA Mutational Analysis
  • Gene Deletion
  • Genes, Recessive / genetics*
  • Genetic Carrier Screening / methods
  • Genotype
  • Hearing Loss / ethnology*
  • Hearing Loss / genetics*
  • Heterozygote
  • Humans
  • Morocco
  • Pedigree
  • Point Mutation / genetics*
  • Polymerase Chain Reaction

Substances

  • Connexins
  • GJB2 protein, human
  • Connexin 26