title: Mutations in the KCNQ4 gene are responsible for autosomal dominant deafness in four DFNA2 families.
abstract: We have previously found linkage to chromosome 1p34 in five large families with autosomal dominant non-syndromic hearing impairment (DFNA2). In all five families, the connexin31 gene ( GJB3 ), located at 1p34 and responsible for non-syndromic autosomal dominant hearing loss in two small Chinese families, 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 was mapped to chromosome 1p34 and a single mutation was found in three patients 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 fourth family. No KCNQ4 mutation could be found in a single DFNA2 family of Indonesian origin. These results indicate that at least two and possibly three genes responsible for hearing impairment are located close together on chromosome 1p34 and suggest that KCNQ4 mutations may be a relatively frequent cause of autosomal dominant hearing loss.
authors.affiliation: Department of Medical Genetics, University of Antwerp-UIA, Universiteitsplein 1, 2610 Antwerp, Belgium,
authors.forename: P J
authors.initials: PJ
authors.lastname: Coucke
authors.forename: P
authors.initials: P
authors.lastname: Van Hauwe
authors.forename: P M
authors.initials: PM
authors.lastname: Kelley
authors.forename: H
authors.initials: H
authors.lastname: Kunst
authors.forename: I
authors.initials: I
authors.lastname: Schatteman
authors.forename: D
authors.initials: D
authors.lastname: Van Velzen
authors.forename: J
authors.initials: J
authors.lastname: Meyers
authors.forename: R J
authors.initials: RJ
authors.lastname: Ensink
authors.forename: M
authors.initials: M
authors.lastname: Verstreken
authors.forename: F
authors.initials: F
authors.lastname: Declau
authors.forename: H
authors.initials: H
authors.lastname: Marres
authors.forename: K
authors.initials: K
authors.lastname: Kastury
authors.forename: S
authors.initials: S
authors.lastname: Bhasin
authors.forename: W T
authors.initials: WT
authors.lastname: McGuirt
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: C W
authors.initials: CW
authors.lastname: Cremers
authors.forename: P
authors.initials: P
authors.lastname: Van de Heyning
authors.forename: P J
authors.initials: PJ
authors.lastname: Willems
authors.forename: S D
authors.initials: SD
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
mesh_terms: D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004252:DNA Mutational Analysis; D003638:Deafness / Q000235:genetics*; D020224:Expressed Sequence Tags; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D051656:KCNQ Potassium Channels; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D005819:Genetic Markers; D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated