Refined mapping of the autosomal recessive non-syndromic deafness locus DFNB13 using eight novel microsatellite markers

Abstract

The locus for a type of an autosomal recessive non-syndromic deafness (ARND), DFNB13, was previously mapped to a 17-cm interval of chromosome 7q34-36. We identified two consanguineous Tunisian families with severe to profound ARND. Linkage analyses with microsatellites surrounding the previously identified loci detected linkage with markers corresponding to the DFNB13 locus in both families. Haplotype analyses assigned this locus to a 3.2-Mb region between markers D7S2468 and D7S2473. In order to refine this interval, we identified nine dinucleotide repeats in the 7q34 region. To investigate the polymorphism of these repeats, a population study of 74 unrelated individuals from different regions of Tunisia was carried out. Our results demonstrated that eight of the nine repeats are polymorphic. The average number of alleles at these informative loci was 9.12 with a polymorphism information content of 0.71. Little evidence for linkage disequilibrium between some marker pairs was found. Haplotype analysis using these microsatellites refined the DFNB13 interval to an area of 2.2 Mb between the D7S5377 and D7S2473. In order to identify the DFNB13 gene, we sequenced and eliminated three candidate genes. Other known and predicted genes are being screened for deafness-causing mutations.