Genetics of familial hypercholesterolemia: updated criteria for LDLR gene variant interpretation


Authors: Lukáš Tichý 1;  Kateřina Konečná 2;  Tomáš Freiberger 3,4
Authors‘ workplace: Centrum molekulární biologie a genetiky, Interní hematologická a onkologická klinika LF MU a FN Brno 1;  Národní centrum pro výzkum biomolekul, Přírodovědecká fakulta MU, Brno 2;  Centrum kardiovaskulární a transplantační chirurgie Brno 3;  Ústav klinické imunologie a alergologie LF MU a FN u sv. Anny v Brně 4
Published in: AtheroRev 2021; 6(3): 168-172
Category:

Overview

Familial hypercholesterolemia is one of the most common metabolic diseases. It is mostly associated with pathogenic variants in the LDLR gene. Public databases contain more than 3,000 sequence variants that have been reported in this gene worldwide. Despite crucial technological advances in molecular biology, the interpretation of detected sequence variants in relation to the specific evaluated clinical phenotype in a particular patient remains a key task. Within an international expert group, criteria for evaluation of causality of sequence variants in the LDLR gene were developed to unify different interpretation algorithms. These criteria should then be applied to the clinical and diagnostic practice.

Keywords:

LDLR – familial hypercholesterolemia – evaluation criteria – pathogenic variants


Sources
  1. Beheshti SO, Madsen CM, Varbo A et al. Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects. J Am Coll Cardiol 2020; 75(20): 2553–2566. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2020.03.057>.
  2. Tichý L, Fajkusová L, Zapletalová P et al. Molecular genetic background of an autosomal dominant hypercholesterolemia in the Czech Republic. Physiol Res 2017; 66(Suppl 1): S47-S54. Dostupné z DOI: <http://dx.doi.org/10.33549/physiolres.933587>.
  3. Vrablík M, Bláha V, Cífková R et al. Genetické testování familiární hypercholesterolemie v klinické praxi: stanovisko výboru České společnosti pro aterosklerózu. AtheroRev 2020; 5(3): 147–157.
  4. Vaverkova H, Tichy L, Karasek D et al. A case of autosomal recessive hypercholesterolemia caused by a new variant in the LDL receptor adaptor protein 1 gene. J Clin Lipidol 2019; 13(3): 405–410. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacl.2019.02.003>.
  5. Floriánková M, Urbanová Z, Bláhová Š et al. Sitosterolémie: klinická, biochemická a molekulárně genetická charakteristika 3letého chlapce s významnou hypercholesterolémií. Čes-Slov Pediat 2017; 72(8): 495–503.
  6. Urbánek R, Tichý L, Freiberger T. Tangierská nemoc v rodině s fenotypem familiární hypercholesterolemie. [Tangier disease in family with the phenotype of familial hypercholesterolemia]. Vnitr Lek 2020; 66(7): 443–446. Dostupné z DOI: <doi: 10.36290/vnl.2020.125>.
  7. National Center for Biotechnology Information [online]. Dostupné z WWW: <https://www.ncbi.nlm.nih.gov/clinvar>.
  8. Iacocca MA, Chora JR, Carrié A et al. ClinVar database of global familial hypercholesterolemia-associated DNA variants. Hum Mutat 2018; 39(11): 1631–1640. Dostupné z DOI: <http://dx.doi.org/10.1002/humu.23634>.
  9. Chora JR, Iacocca MA, Tichy L et al. The Clinical Genome Resource (ClinGen) Familial Hypercholesterolemia Variant Curation Expert Panel consensus guidelines for LDLR variant classification. Genet Med 2021 (in press).
  10. Richards S, Aziz N, Bale S et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015; 17(5): 405–424. Dostupné z DOI: <http://dx.doi.org/10.1038/gim.2015.30>.
Labels
Angiology Diabetology Internal medicine Cardiology General practitioner for adults
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account