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Background: Hearing impairment (HI) is defined as inability to hear and is an extremely heterogeneous genetic disorder. HI is divided into syndromic (if associated with clinical manifestation in addition to hearing impairment) and non-syndromic forms. So far one hundred and seventeen loci/genes have been mapped for non-syndromic HI and mutations in DFNB1 locus (GJB2 gene) are the most prevalent cause among them. This study was intended to find the relative contribution of the DFNB1 locus/ GJB2 gene for hearing loss in Pakistan and Azad Kashmir. Methods: Twenty-one families were collected from different rural and urban regions of Pakistan and Azad Kashmir. The contribution of GJB2 gene was initially studied by linkage analysis using short tandem repeats (STR) microsatellite markers. Sanger sequencing was employed to identify the causative variants in coding region of the gene. Results: Phenotype of four families were found linked with GJB2 gene and all affected individuals of these families segregating same mutation c.231G>A (p.Trp77*) which was confirmed after Sanger sequencing. Conclusion: The genetic causes of hearing impairment were studied in twenty one families segregating autosomal recessive pattern of inheritance with different ethnicities. We further established the founder effect for the one recurrent mutation in GJB2 gene in Pakistani and Kashmiri hearing impaired families for the very first time.

Hamna Tariq, Kalsoom Zaigham, Samra Kousar, Aysha Azhar. (2019) Genetic contribution of GJB2 gene to hearing impairment in Pakistan, Advancements in Life Sciences, Volume 7, Issue1.
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