Muscular dystrophies.

Muscular dystrophies are a heterogeneous group of inherited disorders characterized by progressive muscle wasting and weakness. Majority of genes and their protein products responsible for the dystrophies have been identified in recent years. Using molecular studies, now it is possible to establish a precise diagnosis, provide prognosis, detect preclinical cases, identify carriers, and offer prenatal diagnostic testing. Molecular genetic approaches also seem to offer the best prospect for developing effective treatments in the future.

Connexin 26 and autosomal recessive non-syndromic hearing loss.

Prelingual deafness occurs with a frequency of 1 in 1000 live births and is divided into syndromic and non-syndromic forms contributing 40 and 60% respectively. Autosomal recessive non-syndromic hearing loss (ARNSHL) is responsible for 80% cases of childhood deafness. Nearly all genes localized for ARNSHL cause prelingual, severe to profound, sensorineural hearing impairment. ARNSHL is genetically heterogeneous and at least 39 loci have been identified. The most significant finding to date has been the discovery of mutations in GJB2 gene at the DFNB1 locus on chromosome 13q12 as the major cause of profound prelingual deafness. This was first reported in a Tunisian family in 1994 and thereafter in many different countries. GJB2 gene encodes the gap-junction protein, connexin 26 (Cx26), mutations in which have become the first genetic marker of inherited hearing loss. Allele-specific polymerase chain reaction (AS-PCR), single stranded conformation polymorphism (SSCP) and sequencing methods have been developed for the detection of mutations in Cx26 gene. In India as well, the Cx26 mutations are being screened in families with hearing impaired children using these molecular methods. Therefore, in order to create awareness among the clinicians and the affected families; we have attempted to review the Cx26 gene mutations responsible for autosomal recessive type of non-syndromic hearing loss. The efficacy and utility of Cx26 gene analysis might open the path to proper counseling of families for carrier detection and prenatal diagnosis. It may even facilitate the development of strategies in future for the treatment of this common genetic disorder.