The c.IVS1+1G>A mutation intheGJB2 gene is prevalent and large deletions involving theGJB6 gene are not present in the Turkish population

Abstract

Listen

Translate article

Congenital hearing loss is the most common sensorial problem, affecting approximately one in 500 children. Genetic factors are believed to be causative in at least half of these children. Although significant genetic heterogeneity exists as the cause of sensorineural hearing loss, one locus, DFNB1, comprising the GJB2 and GJB6 genes, is responsible for up to 20–50% of cases with congenital nonsyndromic hearing loss in many populations (Kelsell et al. 1997; Kenneson et al. 2002). Homozygous or compound heterozygous mutations in GJB2 are detected in most cases with DFNB1-related hearing loss. It was, nevertheless, evident in some studies that up to 50% of deaf subjects with GJB2 mutations carried only one mutant allele. During the search for an accompanying mutation in these heterozygotes, a large deletion of about 342 kb (later corrected to be 309 kb), which does not include GJB2 but truncates the neighboring GJB6, was discovered (Lerer et al. 2001; Del Castillo et al. 2002; Pallares-Ruiz et al. 2002). This large deletion, referred to as del(GJB6-D13S1830), was found to be located in trans in about 50% of Spanish individuals with nonsyndromic congenital or prelingual hearing loss with only one heterozygous mutation in GJB2 (Del Castillo et al. 2002). Significant differences in the frequency of this deletion among probands with sensorineural hearing loss have been reported in different populations. It was found to be common in Spain, France, the United Kingdom, Israel and Brazil, less frequent in the United States, Belgium and Australia, and detected in only a few individuals in Germany and the Czech Republic (Gabriel et al. 2001; Del Castillo et al. 2005; Seeman et al. 2005). It was not found in Austria and China (Gunther et al. 2002; Liu et al. 2002). It is remarkable that different frequencies have