A comprehensive study to determine heterogeneity of autosomal recessive nonsyndromic hearing loss in Iran

Am J Med Genet A. 2012 Oct;158A(10):2485-92. doi: 10.1002/ajmg.a.35572. Epub 2012 Aug 17.

Abstract

Hearing loss is the most common sensory disorder worldwide and affects 1 of every 500 newborns. In developed countries, at least 50% of cases are genetic, most often resulting in nonsyndromic deafness (70%), which is usually autosomal recessive (∼80%). Although the cause of hearing loss is heterogeneous, mutations in GJB2 gene at DFNB1 locus are the major cause of autosomal recessive nonsyndromic hearing loss (ARNSHL) in many populations. Our previous study showed that mutations of GJB2 gene do not contribute to the major genetic load of deafness in the Iranian population (∼16%). Therefore, to define the importance of other genes in contributing to an ARNSHL phenotype in the Iranian population, we used homozygosity mapping to identify regions of autozygosity-by-descent in 144 families which two or more progeny had ARNSHL but were negative for GJB2 gene mutations. Using flanking or intragenic short-tandem repeat markers for 33 loci we identified 33 different homozygous variations in 10 genes, of which 9 are novel. In aggregate, these data explain ∼40% of genetic background of ARNHSL in the Iranian population.

MeSH terms

  • Chromosome Mapping
  • Connexin 26
  • Connexins
  • Family
  • Genes, Recessive*
  • Hearing Loss, Sensorineural / epidemiology*
  • Hearing Loss, Sensorineural / genetics*
  • Homozygote*
  • Humans
  • Iran / epidemiology
  • Microsatellite Repeats / genetics*
  • Mutation

Substances

  • Connexins
  • GJB2 protein, human
  • Connexin 26

Supplementary concepts

  • Nonsyndromic sensorineural hearing loss