Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families

Citation
Pj. Coucke et al., Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families, HUM MOL GEN, 8(7), 1999, pp. 1321-1328
Citations number
35
Categorie Soggetti
Molecular Biology & Genetics
Journal title
HUMAN MOLECULAR GENETICS
ISSN journal
09646906 → ACNP
Volume
8
Issue
7
Year of publication
1999
Pages
1321 - 1328
Database
ISI
SICI code
0964-6906(199907)8:7<1321:MITKGA>2.0.ZU;2-#
Abstract
We have previously found linkage to chromosome 1p34 in five large families with autosomal dominant non-syndromic hearing impairment (DFNA2), In all fi ve families, the connexin31 gene (GJB3), located at 1p34 and responsible fo r non-syndromic autosomal dominant hearing loss in two small Chinese famili es, has been excluded as the responsible gene. Recently, a fourth member of the KCNQ branch of the K+ channel family, KCNQ4, has been cloned, KCNQ4 wa s mapped to chromosome 1p34 and a single mutation was found in three patien ts from a small French family with non-syndromic autosomal dominant hearing loss. In this study, we have analysed the KCNQ4 gene for mutations in our five DFNA2 families, Missense mutations altering conserved amino acids were found in three families and an inactivating deletion was present in a four th family, No KCNQ4 mutation could be found in a single DFNA2 family of Ind onesian origin. These results indicate that at least two and possibly three genes responsible for hearing impairment are located close together on chr omosome 1p34 and suggest that KCNQ4 mutations may be a relatively frequent cause of autosomal dominant hearing loss.