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The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification.
Chora, Joana R; Iacocca, Michael A; Tichý, Lukás; Wand, Hannah; Kurtz, C Lisa; Zimmermann, Heather; Leon, Annette; Williams, Maggie; Humphries, Steve E; Hooper, Amanda J; Trinder, Mark; Brunham, Liam R; Costa Pereira, Alexandre; Jannes, Cinthia E; Chen, Margaret; Chonis, Jessica; Wang, Jian; Kim, Serra; Johnston, Tami; Soucek, Premysl; Kramarek, Michal; Leigh, Sarah E; Carrié, Alain; Sijbrands, Eric J; Hegele, Robert A; Freiberger, Tomás; Knowles, Joshua W; Bourbon, Mafalda.
Afiliação
  • Chora JR; Department of Health Promotion and Prevention of Noncommunicable Diseases, Nacional Institute of Health Dr. Ricardo Jorge, Lisbon, Portugal; BioISI - BioSystems & Integrative Sciences Institute, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
  • Iacocca MA; Departments of Biomedical Data Science and Pathology, School of Medicine, Stanford University, Stanford, CA; Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto Ontario, Canada.
  • Tichý L; Centre of Molecular Biology and Gene Therapy, University Hospital Brno, Brno, Czech Republic.
  • Wand H; Departments of Biomedical Data Science and Pathology, School of Medicine, Stanford University, Stanford, CA; Center for Inherited Cardiovascular Disease, Stanford Health Care, Stanford University, Stanford, CA.
  • Kurtz CL; Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC.
  • Zimmermann H; Ambry Genetics, Aliso Viejo, CA.
  • Leon A; Color Health, Inc, Burlingame, CA.
  • Williams M; Bristol Genetics Laboratory, North Bristol NHS Trust, Bristol, United Kingdom.
  • Humphries SE; Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, United Kingdom.
  • Hooper AJ; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, University of Western Australia, Perth, Western Australia, Australia.
  • Trinder M; Department of Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
  • Brunham LR; Department of Medicine, Faculty of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada.
  • Costa Pereira A; Laboratory of Genetics and Molecular Cardiology, Institute of the Hearth (InCor), Faculty of Medicine, São Paulo University, São Paulo, Brazil.
  • Jannes CE; Laboratory of Genetics and Molecular Cardiology, Institute of the Hearth (InCor), Faculty of Medicine, São Paulo University, São Paulo, Brazil.
  • Chen M; GeneDx, Inc, Gaithersburg, MD.
  • Chonis J; GeneDx, Inc, Gaithersburg, MD.
  • Wang J; Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
  • Kim S; Color Health, Inc, Burlingame, CA.
  • Johnston T; Ambry Genetics, Aliso Viejo, CA.
  • Soucek P; Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic.
  • Kramarek M; Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic.
  • Leigh SE; Genomics England, London, United Kingdom.
  • Carrié A; University Hospitals Pitié-Salpêtrière/Charles-Foix, Molecular and Chromosomal Genetics Center, Obesity and Dyslipidemia Genetics Unit, Sorbonne University, Paris, France.
  • Sijbrands EJ; Academic Medical Center, Erasmus University, Rotterdam, Netherlands.
  • Hegele RA; Robarts Research Institute, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.
  • Freiberger T; Centre for Cardiovascular Surgery and Transplantation, Brno, Czech Republic; Faculty of Medicine, Masaryk University, Brno, Czech Republic.
  • Knowles JW; Division of Cardiovascular Medicine, Stanford Cardiovascular Institute, Prevention Research Center, and Diabetes Research Center, School of Medicine, Stanford University, Stanford, CA; FH Foundation, Pasadena, CA.
  • Bourbon M; Department of Health Promotion and Prevention of Noncommunicable Diseases, Nacional Institute of Health Dr. Ricardo Jorge, Lisbon, Portugal; BioISI - BioSystems & Integrative Sciences Institute, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
Genet Med ; 24(2): 293-306, 2022 02.
Article em En | MEDLINE | ID: mdl-34906454
PURPOSE: In 2015, the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) published consensus standardized guidelines for sequence-level variant classification in Mendelian disorders. To increase accuracy and consistency, the Clinical Genome Resource Familial Hypercholesterolemia (FH) Variant Curation Expert Panel was tasked with optimizing the existing ACMG/AMP framework for disease-specific classification in FH. In this study, we provide consensus recommendations for the most common FH-associated gene, LDLR, where >2300 unique FH-associated variants have been identified. METHODS: The multidisciplinary FH Variant Curation Expert Panel met in person and through frequent emails and conference calls to develop LDLR-specific modifications of ACMG/AMP guidelines. Through iteration, pilot testing, debate, and commentary, consensus among experts was reached. RESULTS: The consensus LDLR variant modifications to existing ACMG/AMP guidelines include (1) alteration of population frequency thresholds, (2) delineation of loss-of-function variant types, (3) functional study criteria specifications, (4) cosegregation criteria specifications, and (5) specific use and thresholds for in silico prediction tools, among others. CONCLUSION: Establishment of these guidelines as the new standard in the clinical laboratory setting will result in a more evidence-based, harmonized method for LDLR variant classification worldwide, thereby improving the care of patients with FH.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Genoma Humano / Hiperlipoproteinemia Tipo II Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Revista: Genet Med Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Genoma Humano / Hiperlipoproteinemia Tipo II Tipo de estudo: Guideline / Prognostic_studies Limite: Humans Idioma: En Revista: Genet Med Ano de publicação: 2022 Tipo de documento: Article