title: Mutational screening of the USH2A gene in Spanish USH patients reveals 23 novel pathogenic mutations.
abstract: BACKGROUND
  Usher Syndrome type II (USH2) is an autosomal recessive disorder, characterized by moderate to severe hearing impairment and retinitis pigmentosa (RP). Among the three genes implicated, mutations in the USH2A gene account for 74-90% of the USH2 cases.
  
  
  METHODS
  To identify the genetic cause of the disease and determine the frequency of USH2A mutations in a cohort of 88 unrelated USH Spanish patients, we carried out a mutation screening of the 72 coding exons of this gene by direct sequencing. Moreover, we performed functional minigene studies for those changes that were predicted to affect splicing.
  
  
  RESULTS
  As a result, a total of 144 DNA sequence variants were identified. Based upon previous studies, allele frequencies, segregation analysis, bioinformatics' predictions and in vitro experiments, 37 variants (23 of them novel) were classified as pathogenic mutations.
  
  
  CONCLUSIONS
  This report provide a wide spectrum of USH2A mutations and clinical features, including atypical Usher syndrome phenotypes resembling Usher syndrome type I. Considering only the patients clearly diagnosed with Usher syndrome type II, and results obtained in this and previous studies, we can state that mutations in USH2A are responsible for 76.1% of USH2 disease in patients of Spanish origin.
authors: Grupo de Investigación en Enfermedades Neurosensoriales, Instituto de Investigación Sanitaria IIS-La Fe, Valencia, Spain.
authors: Gema
authors: G
authors: Garcia-Garcia
authors: Maria J
authors: MJ
authors: Aparisi
authors: Teresa
authors: T
authors: Jaijo
authors: Regina
authors: R
authors: Rodrigo
authors: Ana M
authors: AM
authors: Leon
authors: Almudena
authors: A
authors: Avila-Fernandez
authors: Fiona
authors: F
authors: Blanco-Kelly
authors: Sara
authors: S
authors: Bernal
authors: Rafael
authors: R
authors: Navarro
authors: Manuel
authors: M
authors: Diaz-Llopis
authors: Montserrat
authors: M
authors: Baiget
authors: Carmen
authors: C
authors: Ayuso
authors: Jose M
authors: JM
authors: Millan
authors: Elena
authors: E
authors: Aller
mesh_terms: D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005091:Exons; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D010641:Phenotype; D013030:Spain; D052245:Usher Syndromes / Q000145:classification / Q000235:genetics*; D055815:Young Adult
chemical_list: D016326:Extracellular Matrix Proteins; C112735:USH2A protein, human