novel tmprss3 variants in pakistani families with autosomal recessive nonsyndromic hearing impairment mutations in the tmprss3 gene are known to cause autosomal recessive nonsyndromic hearing impairment arnshi after undergoing a genome scan 10 consanguineous pakistani families with arnshi were found to have significant or suggestive evidence of linkage to the tmprss3 region in order to elucidate if the tmprss3 gene is responsible for arnshi in these families the gene was sequenced using dna samples from these families six tmprss3 variants were found to cosegregate in 10 families none of these variants were detected in 500 control chromosomes four novel variants three of which are missense c310ga pglu104lys c767ct pala256val and c1273tc pcys425arg and one nonsense c310gt pglu104stop were identified the pathogenicity of novel missense variants was investigated through bioinformatics analyses additionally the previously reported deletion c208delc phis70thrfsx19 was identified in one family and the known mutation c1219tc pcys407arg was found in five families which makes c1219tc pcys407arg as the most common tmprss3 mutation within the pakistani population identification of these novel variants lends support to the importance of elements within the lowdensity lipoprotein receptor a ldlra and serine protease domains in structural stability ligand binding and proteolytic activity for proper tmprss3 function within the inner ear