Your browser doesn't support javascript.
loading
Truncating variants in the majority of the cytoplasmic domain of PCDH15 are unlikely to cause Usher syndrome 1F.
Perreault-Micale, Cynthia; Frieden, Alexander; Kennedy, Caleb J; Neitzel, Dana; Sullivan, Jessica; Faulkner, Nicole; Hallam, Stephanie; Greger, Valerie.
Afiliación
  • Perreault-Micale C; Good Start Genetics, Inc., Cambridge, Massachusetts.
  • Frieden A; Good Start Genetics, Inc., Cambridge, Massachusetts.
  • Kennedy CJ; Good Start Genetics, Inc., Cambridge, Massachusetts.
  • Neitzel D; Good Start Genetics, Inc., Cambridge, Massachusetts.
  • Sullivan J; Good Start Genetics, Inc., Cambridge, Massachusetts.
  • Faulkner N; Good Start Genetics, Inc., Cambridge, Massachusetts.
  • Hallam S; Good Start Genetics, Inc., Cambridge, Massachusetts.
  • Greger V; Good Start Genetics, Inc., Cambridge, Massachusetts. Electronic address: vgreger@gsgenetics.com.
J Mol Diagn ; 16(6): 673-8, 2014 Nov.
Article en En | MEDLINE | ID: mdl-25307757
Loss of function variants in the PCDH15 gene can cause Usher syndrome type 1F, an autosomal recessive disease associated with profound congenital hearing loss, vestibular dysfunction, and retinitis pigmentosa. The Ashkenazi Jewish population has an increased incidence of Usher syndrome type 1F (founder variant p.Arg245X accounts for 75% of alleles), yet the variant spectrum in a panethnic population remains undetermined. We sequenced the coding region and intron-exon borders of PCDH15 using next-generation DNA sequencing technology in approximately 14,000 patients from fertility clinics. More than 600 unique PCDH15 variants (single nucleotide changes and small indels) were identified, including previously described pathogenic variants p.Arg3X, p.Arg245X (five patients), p.Arg643X, p.Arg929X, and p.Arg1106X. Novel truncating variants were also found, including one in the N-terminal extracellular domain (p.Leu877X), but all other novel truncating variants clustered in the exon 33 encoded C-terminal cytoplasmic domain (52 patients, 14 variants). One variant was observed predominantly in African Americans (carrier frequency of 2.3%). The high incidence of truncating exon 33 variants indicates that they are unlikely to cause Usher syndrome type 1F even though many remove a large portion of the gene. They may be tolerated because PCDH15 has several alternate cytoplasmic domain exons and differentially spliced isoforms may function redundantly. Effects of some PCDH15 truncating variants were addressed by deep sequencing of a panethnic population.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cadherinas / Citoplasma / Síndromes de Usher Límite: Humans Idioma: En Revista: J Mol Diagn Asunto de la revista: BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cadherinas / Citoplasma / Síndromes de Usher Límite: Humans Idioma: En Revista: J Mol Diagn Asunto de la revista: BIOLOGIA MOLECULAR Año: 2014 Tipo del documento: Article Pais de publicación: Estados Unidos