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Identification of Rare Genetic Variants in Familial Spontaneous Coronary Artery Dissection and Evidence for Shared Biological Pathways.
Turley, Tamiel N; Theis, Jeanne L; Evans, Jared M; Fogarty, Zachary C; Gulati, Rajiv; Hayes, Sharonne N; Tweet, Marysia S; Olson, Timothy M.
Afiliación
  • Turley TN; Molecular Pharmacology and Experimental Therapeutics Track, Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN 55905, USA.
  • Theis JL; Cardiovascular Genetics Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
  • Evans JM; Cardiovascular Genetics Research Laboratory, Mayo Clinic, Rochester, MN 55905, USA.
  • Fogarty ZC; Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN 55905, USA.
  • Gulati R; Department of Quantitative Health Sciences, Division of Computational Biology, Mayo Clinic, Rochester, MN 55905, USA.
  • Hayes SN; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Tweet MS; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
  • Olson TM; Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA.
J Cardiovasc Dev Dis ; 10(9)2023 Sep 12.
Article en En | MEDLINE | ID: mdl-37754822
Rare familial spontaneous coronary artery dissection (SCAD) kindreds implicate genetic disease predisposition and provide a unique opportunity for candidate gene discovery. Whole-genome sequencing was performed in fifteen probands with non-syndromic SCAD who had a relative with SCAD, eight of whom had a second relative with extra-coronary arteriopathy. Co-segregating variants and associated genes were prioritized by quantitative variant, gene, and disease-level metrics. Curated public databases were queried for functional relationships among encoded proteins. Fifty-four heterozygous coding variants in thirteen families co-segregated with disease and fulfilled primary filters of rarity, gene variation constraint, and predicted-deleterious protein effect. Secondary filters yielded 11 prioritized candidate genes in 12 families, with high arterial tissue expression (n = 7), high-confidence protein-level interactions with genes associated with SCAD previously (n = 10), and/or previous associations with connective tissue disorders and aortopathies (n = 3) or other vascular phenotypes in mice or humans (n = 11). High-confidence associations were identified among 10 familial SCAD candidate-gene-encoded proteins. A collagen-encoding gene was identified in five families, two with distinct variants in COL4A2. Familial SCAD is genetically heterogeneous, yet perturbations of extracellular matrix, cytoskeletal, and cell-cell adhesion proteins implicate common disease-susceptibility pathways. Incomplete penetrance and variable expression suggest genetic or environmental modifiers.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: J Cardiovasc Dev Dis Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Diagnostic_studies / Prognostic_studies Idioma: En Revista: J Cardiovasc Dev Dis Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Suiza