title: Mutation screening of the PCDH15 gene in Spanish patients with Usher syndrome type I.
abstract: OBJECTIVE
  PCDH15 codes for protocadherin-15, a cell-cell adhesion protein essential in the morphogenesis and cohesion of stereocilia bundles and in the function or preservation of photoreceptor cells. Mutations in the PCDH15 gene are responsible for Usher syndrome type I (USH1F) and non-syndromic hearing loss (DFNB23). The purpose of this work was to perform PCDH15 mutation screening to identify the genetic cause of the disease in a cohort of Spanish patients with Usher syndrome type I and establish phenotype-genotype correlation.
  
  
  METHODS
  Mutation analysis of PCDH15 included additional exons recently identified and was performed by direct sequencing. The screening was performed in 19 probands with USH already screened for mutations in the most prevalent USH1 genes, myosin VIIA (MYO7A) and cadherin-23 (CDH23), and for copy number variants in PCDH15.
  
  
  RESULTS
  Seven different point mutations, five novel, were detected. Including the large PCDH15 rearrangements previously reported in our cohort of patients, a total of seven of 19 patients (36.8%) were carriers of at least one pathogenic allele. Thirteen out of the 38 screened alleles carried pathogenic PCDH15 variants (34.2%).
  
  
  CONCLUSIONS
  Five out of the seven point mutations reported in the present study are novel, supporting the idea that most PCDH15 mutations are private. Furthermore, no mutational hotspots have been identified. In most patients, detected mutations led to a truncated protein, reinforcing the hypothesis that severe mutations cause the Usher I phenotype and that missense variants are mainly responsible for non-syndromic hearing impairment.
authors: Grupo de Investigación en Enfermedades Neurosensoriales. Instituto de Investigación Sanitaria IIS- La Fe, Avda. Campanar 21, Valencia, Spain.
authors: Teresa
authors: T
authors: Jaijo
authors: Aki
authors: A
authors: Oshima
authors: Elena
authors: E
authors: Aller
authors: Carol
authors: C
authors: Carney
authors: Shin-ichi
authors: S
authors: Usami
authors: José M
authors: JM
authors: Millán
authors: William J
authors: WJ
authors: Kimberling
mesh_terms: D000483:Alleles; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D013030:Spain; D052245:Usher Syndromes / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C498835:CDHR15, human; D000070585:Cadherin Related Proteins; D015820:Cadherins