title: USH2A mutation analysis in 70 Dutch families with Usher syndrome type II.
abstract: Usher syndrome type II (USH2) is characterised by moderate to severe high-frequency hearing impairment, progressive visual loss due to retinitis pigmentosa and intact vestibular responses. Three loci are known for USH2, however, only the gene for USH2a (USH2A) has been identified. Mutation analysis of USH2A was performed in 70 Dutch USH2 families. Ten mutations in USH2A were detected, of which three are novel, c.949C>A, c.2242C>T (p.Gln748X) and c.4405C>T (p.Gln1468X). Including 9 previously published Dutch USH2a families, estimates of the prevalence of USH2a in the Dutch USH2 population were made. Mutations were identified in 62% of the families. In 28% both mutated alleles were identified, whereas in 34% the mutation in only one allele was found. It is estimated that about 28% of the Dutch USH2 families have a different causative gene. Analysis of deduced haplotypes suggests that c.1256G>T (p.Cys419Phe) is a Dutch ancestral mutation, occurring in 16% of the alleles.
authors.affiliation: Department of Otorhinolaryngology, UMC Nijmegen, The Netherlands. r.pennings@kno.umcn.nl
authors.forename: Ronald J E
authors.initials: RJ
authors.lastname: Pennings
authors.forename: Heleen
authors.initials: H
authors.lastname: Te Brinke
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weston
authors.forename: Annemarie
authors.initials: A
authors.lastname: Claassen
authors.forename: Dana J
authors.initials: DJ
authors.lastname: Orten
authors.forename: Henriëtte
authors.initials: H
authors.lastname: Weekamp
authors.forename: Annelies
authors.initials: A
authors.lastname: Van Aarem
authors.forename: Patrick L M
authors.initials: PL
authors.lastname: Huygen
authors.forename: August F
authors.initials: AF
authors.lastname: Deutman
authors.forename: Lies H
authors.initials: LH
authors.lastname: Hoefsloot
authors.forename: Frans P M
authors.initials: FP
authors.lastname: Cremers
authors.forename: Cor W R J
authors.initials: CW
authors.lastname: Cremers
authors.forename: William J
authors.initials: WJ
authors.lastname: Kimberling
authors.forename: Hannie
authors.initials: H
authors.lastname: Kremer
mesh_terms: D004252:DNA Mutational Analysis / Q000379:methods*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D016326:Extracellular Matrix Proteins; D005819:Genetic Markers; C112735:USH2A protein, human