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
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.