DFNA49, a novel locus for autosomal dominant non-syndromic hearing loss, maps proximal to DFNA7/DFNM1 region on chromosome 1q21-q23

Abstract

Autosomal dominant inheritance accounts for about 20% of the cases of hereditary non-syndromic sensorineural hearing loss (NSSHL)—that is, hearing loss not associated with other clinical features. So far, 36 loci have been mapped in familial cases that segregate autosomal dominant NSSHL (DFNA), and 17 genes have been identified. N Here we report the location of a novel autosomal dominant deafness locus on 1q21–q23, DFNA49, found by studying a large Spanish family with nonsyndromic, progressive mid-frequency hearing loss of post-lingual onset. A maximum lod score of 6.02 at h = 0 was obtained for markers D1S3784 and D1S3785. Analysis of recombinant haplotypes placed the deafness locus within a 4 cM region defined by markers GDB:190880 and D1S3786. N This genetic interval is proximal to and does not overlap with the previously identified loci, DFNA7 and DFNM1, on 1q21–q23. N Screening of candidate genes within the DFNA49 interval (KCNJ9, KCNJ10, ATP1A2 and CASQ1) did not reveal the mutation causing this deafness.