Haplotype analysis of DFNB8/10 locus reveals contribution of TMPRSS3 mutations in Pakistani deaf population

摘要

TMPRSS3 mutations are associated with non-syndromic recessive deafness (DFNB8/10). To evaluate the frequency of TMPRSS3 mutation in Pakistani population, highly consanguineous families were enrolled. A group of five consanguineous families without any history of associated environmental causes were found to be linked to DFNB8/10 locus. To correlate haplotypes and to evaluate founder affect 17 other families linked to DFNB8/10 were provided by NCEMB DNA bank. Haploytpe analysis revealed that out of 22 families, haplotypes of 8 families (42 %) were found similar to PKDF003 and PKDF311 having 207delC mutation, 5 (26 %) families had haplotypes similar to PKDF040 and 4 families (15.7 %) shared halpotypes similar to PKDF064, having C407R (1219T > C) and C194F (518G > T) mutations, respectively. Interestingly, PKDF321 and PKDF337 (10.5 %) showed different haplotypes and might harbor novel mutation. Taken together, these data imply that Punjab region is more affected by TMPRSS3 mutation, and the founder-effect mutation might be traced back to Punjab region.