Your browser doesn't support javascript.
loading
Can tandem alternative splicing and evasion of premature termination codon surveillance contribute to attenuated Peutz-Jeghers syndrome?
Gazzaz, Nour; Frost, F Graeme; Alderman, Emily; Richmond, Phillip A; Dalmann, Joshua; Lin, Susan; Salman, Areesha; Del Bel, Kate L; Lehman, Anna; Turvey, Stuart E; Boerkoel, Cornelius F; Cherukuri, Praveen F.
Afiliación
  • Gazzaz N; Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Frost FG; Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi Arabia.
  • Alderman E; National Institutes of Health Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, Maryland, USA.
  • Richmond PA; Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Dalmann J; The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Lin S; The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Salman A; The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Del Bel KL; The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Lehman A; The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Turvey SE; The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Boerkoel CF; The Rare Disease Discovery Hub, BC Children's Hospital Research Institute, University of British Columbia and Children's Hospital of British Columbia, Vancouver, British Columbia, Canada.
  • Cherukuri PF; Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
Am J Med Genet A ; 188(10): 3089-3095, 2022 10.
Article en En | MEDLINE | ID: mdl-35946377
Alternative use of short distance tandem sites such as NAGNn AG are a common mechanism of alternative splicing; however, single nucleotide variants are rarely reported as likely to generate or to disrupt tandem splice sites. We identify a pathogenic intron 5 STK11 variant (NM_000455.4:c.[735-6A>G];[=]) segregating with the mucocutaneous features but not the hamartomatous polyps of Peutz-Jeghers syndrome in two individuals. By RNAseq analysis of peripheral blood mRNA, this variant was shown to generate a novel and preferentially used tandem proximal splice acceptor (AAGTGAAG). The variant transcript (NM_000455.4:c.734_734 + 1insTGAAG), which encodes a frameshift (p.[Tyr246Glufs*43]) constituted 36%-43% of STK11 transcripts suggesting partial escape from nonsense mediated mRNA decay and translation of a truncated protein. A review of the ClinVar database identified other similar variants. We suggest that nucleotide changes creating or disrupting tandem alternative splice sites are a pertinent disease mechanism and require contextualization for clinical reporting. Additionally, we hypothesize that some pathogenic STK11 variants cause an attenuated phenotype.
Asunto(s)
Palabras clave
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: Síndrome de Peutz-Jeghers Tipo de estudio: Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Am J Med Genet A Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Canadá 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: Síndrome de Peutz-Jeghers Tipo de estudio: Prognostic_studies / Screening_studies Límite: Humans Idioma: En Revista: Am J Med Genet A Asunto de la revista: GENETICA MEDICA Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos