A mutational hot spot in the KCNQ4 gene responsible for autosomal dominant hearing impairment.
Several different mutations in the KCNQ4 K+ channel gene are responsible for autosomal dominant nonsyndromic hearing impairment (DFNA2). Here we describe two additional families originating from Europe and Japan with a KCNQ4 missense mutation (W276S) that was previously found in one European family. We compared the disease-associated haplotype of the three W276S-bearing families using closely linked microsatellite markers and intragenic single nucleotide polymorphisms. Differences between the haplotypes were found, excluding a single founder mutation for the families. Therefore, the W276S mutation has occurred three times independently, and most likely represents a hot spot for mutation in the KCNQ4 gene.
Van Camp
Guy
G
Department of Medical Genetics, University of Antwerp-UIA, Antwerp, Belgium. guy.vancamp@ua.ac.be
Coucke
Paul J
PJ
Akita
Jiro
J
Fransen
Erik
E
Abe
Satoko
S
De Leenheer
Els M R
EM
Huygen
Patrick L M
PL
Cremers
Cor W R J
CW
Usami
Shin-Ichi
S
D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D005799:Genes, Dominant; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007564:Japan; D051656:KCNQ Potassium Channels; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D020125:Mutation, Missense; D010375:Pedigree; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated
D051656:KCNQ Potassium Channels; C117367:KCNQ4 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D004247:DNA