title: Linkage analysis of progressive hearing loss in five extended families maps the DFNA2 gene to a 1.25-Mb region on chromosome 1p.
abstract: Thus far, 13 genes for autosomal dominant hearing loss have been localized to specific chromosomal regions, but none of the genes has been cloned. Only a single family has been linked to each of these loci, with the exception of DFNA2. DFNA2 was originally mapped in two extended families originating from Indonesia and the United States. In this study we report linkage to DFNA2 in three additional large families with autosomal dominant hearing loss from Belgium and The Netherlands. These five DFNA2 families show a similar progressive sensorineural hearing loss, starting in the high frequencies and also affecting the middle and low frequencies later in life. Combining the information from all linked families, the candidate region that is most likely to contain the DFNA2 gene was reduced to a 1.25-Mb region between markers D1S432 and MYCL1. Different haplotypes segregating with the hearing loss were found in all five families, suggesting that different mutations are present in the same gene. These results indicate that DFNA2 is most likely an important gene for autosomal dominant hearing loss.
authors.affiliation: Department of Medical Genetics, University of Antwerp-UIA, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Van Camp
authors.forename: P J
authors.initials: PJ
authors.lastname: Coucke
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: H
authors.initials: H
authors.lastname: Marres
authors.forename: M
authors.initials: M
authors.lastname: van Ewijk
authors.forename: F
authors.initials: F
authors.lastname: Declau
authors.forename: P
authors.initials: P
authors.lastname: Van Hauwe
authors.forename: J
authors.initials: J
authors.lastname: Meyers
authors.forename: J
authors.initials: J
authors.lastname: Kenyon
authors.forename: S D
authors.initials: SD
authors.lastname: Smith
authors.forename: R J
authors.initials: RJ
authors.lastname: Smith
authors.forename: B
authors.initials: B
authors.lastname: Djelantik
authors.forename: C W
authors.initials: CW
authors.lastname: Cremers
authors.forename: P H
authors.initials: PH
authors.lastname: Van de Heyning
authors.forename: P J
authors.initials: PJ
authors.lastname: Willems
mesh_terms: D000483:Alleles; D001530:Belgium; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D006239:Haplotypes; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000235:genetics*; D006801:Humans; D007214:Indonesia; D008297:Male; D018895:Microsatellite Repeats; D009426:Netherlands; D010375:Pedigree; D011995:Recombination, Genetic; D014481:United States