Non‐syndromic, autosomal‐recessive deafness

Abstract

Non-syndromic deafness is a paradigm of genetic heterogeneity with 85 loci and 39 nuclear disease genes reported so far. Autosomal-recessive genes are responsible for about 80% of the cases of hereditary non-syndromic deafness of pre-lingual onset with 23 different genes identified to date. In the present article, we review these 23 genes, their function, and their contribution to genetic deafness in different populations. The wide range of functions of these DFNB genes reflects the heterogeneity of the genes involved in hearing and hearing loss. Several of these genes are involved in both recessive and dominant deafness, or in both non-syndromic and syndromic deafness. Mutations in the GJB2 gene encoding connexin 26 are responsible for as much as 50% of pre-lingual, recessive deafness. By contrast, mutations in most of the other DFNB genes have so far been detected in only a small number of families, and their contribution to deafness on a population scale might therefore be limited. Identification of all genes involved in hereditary hearing loss will help in our understanding of the basic mechanisms underlying normal hearing, in early diagnosis and therapy.

Carrier frequency of GJB2 gene mutations c.35delG, c.235delC and c.167delT among the populations of Eurasia

“…It accounts for approximately 40-50% of overall mutant alleles of the GJB2 gene in deaf patients. 37 Earlier, the large-scale research covering 17 European countries demonstrated that the average carrier frequency of c.35delG in Europe was 1.96% (1 of 51), with a variation from 1.26% (1 of 79) in Central and northern Europe to 2.86% (1 of 35) in southern Europe. 7 Further, the gradient of increase in c.35delG frequency from north to south has been confirmed in the meta-analysis of the carrier frequency of c.35delG in various European populations.…”

Preimplantation genetic diagnosis (PGD) for nonsyndromic deafness by polar body and blastomere biopsy

“…In addition, children with cochlear implants show significantly more comorbidity [1]. Hereditary hearing loss occurs in approximately 1/2,000 newborns [2]. More than 50% of pre-lingual deafness in developed countries is attributed to monogenic defects [3] and of these, 50% of nonsyndromic recessive cases are caused by mutations in the GJB2 gene (Connexin 26) [4].…”

Prevalence of GJB2 (Connexin-26) and GJB6 (Connexin-30) Mutations in a Cohort of 300 Brazilian Hearing-Impaired Individuals: Implications for Diagnosis and Genetic Counseling

“…Since 1994, 52 loci associated with recessive hearing loss (HL) have been mapped, and 23 different genes have been identified (The Hereditary Hearing Loss Homepage: http: webhost.ua.ac.be/hhh; Khan, et al, 2006;Petersen & Willems, 2006;Petit, 2006). In spite of this extensive genetic heterogeneity, a single locus, DFNB1 (13q11-q12; OMIM 220290), accounts for up to 50% of nonsyndromic autosomal recessive cases.…”