Biomedical Letters

Genetic contribution of GJB2 gene and DFNB2 locus to hearing impairment in Kashmiri and Pakistani families

Hamna Tariq, Kalsoom Zaigham*

National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

Abstract

Hearing impairment, the inability to hear has heterogeneous etiology. One hundred seventeen genes have been mapped for hearing impairment to date. The present study was aimed to determine the major contribution of the GJB2 and MYO7A for hearing loss in Pakistani and Kashmiri families belonging to different ethnic groups. Twenty-one families were ascertained from different areas of Pakistan and Azad Kashmir. The contribution of GJB2 and MYO7A was initially studied by linkage analysis using short tandem repeats microsatellite markers. Sanger sequencing was further performed for GJB2 (Gap junction beta-2 protein) gene to identify the causative variants. Phenotypes of five families were found linked with these two genes by linkage analysis study (two families with GJB2 and three families with MYO7A). Sanger sequencing of GJB2 resulted in identification of two homozygous recurrent mutations c.71G>A (p. Trp24*) and c.231G>A (p. Trp77*) in two families supporting previous studies. The genetic causes of hearing incapability in 23.80% of all the studied families (5/21) were determined by genotypic and phenotypic expression of autosomal recessive hearing impairment. In this study we established the founder effect for intragenic single nucleotide polymorphism (SNP) haplotypes in families sharing GJB2 gene in Pakistani hearing-impaired families. The founder effect in GJB2 gene is being reported for the very first time in a Kashmiri family.