title: Novel mutations in the USH1C gene in Usher syndrome patients.
abstract: OBJECTIVE
  Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by severe-profound sensorineural hearing loss, retinitis pigmentosa, and vestibular areflexia. To date, five USH1 genes have been identified. One of these genes is Usher syndrome 1C (USH1C), which encodes a protein, harmonin, containing PDZ domains. The aim of the present work was the mutation screening of the USH1C gene in a cohort of 33 Usher syndrome patients, to identify the genetic cause of the disease and to determine the relative involvement of this gene in USH1 pathogenesis in the Spanish population.
  
  
  METHODS
  Thirty-three patients were screened for mutations in the USH1C gene by direct sequencing. Some had already been screened for mutations in the other known USH1 genes (myosin VIIA [MYO7A], cadherin-related 23 [CDH23], protocadherin-related 15 [PCDH15], and Usher syndrome 1G [USH1G]), but no mutation was found.
  
  
  RESULTS
  Two novel mutations were found in the USH1C gene: a non-sense mutation (p.C224X) and a frame-shift mutation (p.D124TfsX7). These mutations were found in a homozygous state in two unrelated USH1 patients.
  
  
  CONCLUSIONS
  In the present study, we detected two novel pathogenic mutations in the USH1C gene. Our results suggest that mutations in USH1C are responsible for 1.5% of USH1 disease in patients of Spanish origin (considering the total cohort of 65 Spanish USH1 patients since 2005), indicating that USH1C is a rare form of USH in this population.
authors.affiliation: Grupo de Investigación en Enfermedades Neurosensoriales, Instituto de Investigación Sanitaria IIS-La Fe, Valencia, Spain.
authors.forename: María José
authors.initials: MJ
authors.lastname: Aparisi
authors.forename: Gema
authors.initials: G
authors.lastname: García-García
authors.forename: Teresa
authors.initials: T
authors.lastname: Jaijo
authors.forename: Regina
authors.initials: R
authors.lastname: Rodrigo
authors.forename: Claudio
authors.initials: C
authors.lastname: Graziano
authors.forename: Marco
authors.initials: M
authors.lastname: Seri
authors.forename: Tulay
authors.initials: T
authors.lastname: Simsek
authors.forename: Enver
authors.initials: E
authors.lastname: Simsek
authors.forename: Sara
authors.initials: S
authors.lastname: Bernal
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
authors.forename: Herminio
authors.initials: H
authors.lastname: Pérez-Garrigues
authors.forename: Elena
authors.initials: E
authors.lastname: Aller
authors.forename: José María
authors.initials: JM
authors.lastname: Millán
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D001483:Base Sequence; D018797:Cell Cycle Proteins; D020090:Chromosome Segregation / Q000235:genetics; D015331:Cohort Studies; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D008040:Genetic Linkage; D056426:Genetic Loci / Q000235:genetics; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics; D010375:Pedigree; D052245:Usher Syndromes / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; C118970:USH1C protein, human; D009218:Myosins