Deafness linked to DFNA2: one locus but how many genes?

Hereditary hearing impairment shows extreme genetic heterogeneity and more than 40 different loci have been reported. One of these, DFNA2, was localized to chromosome 1p34 on the basis of linkage analysis in two large families with autosomal dominant nonsyndromic hearing loss originating from Indonesia and the United States. Subsequently, hearing loss in three additional large families from Belgium and the Netherlands was found to map to the same region. Two different genes are now reported to be the `DFNA2' gene. In December's issue of Nature Genetics, Jia-Hui Xia and colleagues described two small Chinese families with nonsyndromic autosomal dominant hearing loss in which they found a missense and a nonsense mutation in GJB3, which encodes connexin 31 (ref. 3). As GJB3 is located on chromosome 1p34, it was proposed, in an accompanying News & Views that GJB3 is a good candidate for involvement in DFNA2 families. Extensive sequence analysis of the coding region and the 5 theta UTR of GJB3 in all 5 DFNA2 families revealed no mutations, however (data not shown). A recent report in Cell reports the identification of a novel member (KCNQ4) of the potassium channel family KCNQ, also located on chromosome 1p34. Its authors found its mutation to segregate with hearing loss in a small French family, and claimed the identification of the DFNA2 gene.