title: The contribution of USH1C mutations to syndromic and non-syndromic deafness in the UK.
abstract: Denaturing high-performance liquid chromatography (DHPLC) was used to screen 14 UK patients with Usher syndrome type 1, in order to assess the contribution of mutations in USH1C to type 1 Usher. In addition, 16 Caucasian sib pairs and two small consanguineous families with non-syndromic deafness, who were concordant for haplotypes around DFNB18, were also screened for mutations in the USH1C gene. Two Usher type 1 patients were found to have the 238-239insC mutation reported previously; one of Greek Cypriot origin was homozygous for the mutation and another Caucasian was heterozygous. This indicates that mutations in the USH1C gene make a greater contribution to Usher syndrome type 1 than originally thought, which has implications for the genetic testing of families with Usher syndrome in the UK. Analysis using intragenic single nucleotide polymorphisms (SNPs) revealed that the haplotypic background bearing this common mutation was not consistent across the gene in two families, and that there are either two haplotypes on which the mutation has arisen or that there has been a recombination on a single haplotype. We found no evidence of mutations in USH1C in the patients with non-syndromic deafness, suggesting that the gene is not a major contributor to autosomal-recessive non-syndromic deafness in the UK.
authors.affiliation: Clinical and Molecular Genetics Unit, Institute of Child Health, London, UK. D.Blaydon@ich.ucl.ac.uk
authors.forename: D C
authors.initials: DC
authors.lastname: Blaydon
authors.forename: R F
authors.initials: RF
authors.lastname: Mueller
authors.forename: T P
authors.initials: TP
authors.lastname: Hutchin
authors.forename: B P
authors.initials: BP
authors.lastname: Leroy
authors.forename: S S
authors.initials: SS
authors.lastname: Bhattacharya
authors.forename: A C
authors.initials: AC
authors.lastname: Bird
authors.forename: S
authors.initials: S
authors.lastname: Malcolm
authors.forename: M
authors.initials: M
authors.lastname: Bitner-Glindzicz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002851:Chromatography, High Pressure Liquid; D002874:Chromosome Mapping; D003598:Cytoskeletal Proteins; D003638:Deafness / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D013577:Syndrome; D006113:United Kingdom
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C118970:USH1C protein, human