| Title: |
Analysis of routine molecular genetic diagnostics of familial hypercholesterolemia at tertiary care lipid clinics |
| Authors: |
Ferch, M; Galli, L; Fellinger, P; Esterbauer, H; Baumgartner-Parzer, S; Speidl, W; Kautzky-Willer, A; Winhofer, Y |
| Source: |
European Heart Journal ; volume 44, issue Supplement_2 ; ISSN 0195-668X 1522-9645 |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2023 |
| Description: |
Background Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease, causing dyslipidemia and premature atherosclerotic cardiovascular disease (ASCVD), with currently ∼2,000,000 unidentified adult cases as well as ∼500,000 children cases in Europe. Purpose Aim of this study is to analyse the current yield of routine molecular genetic diagnostics for FH and the spectrum of mutations in two specialist lipid clinics. Methods We investigated all genetic tests performed for FH in our clinics over a 4-year period. Reports of causative mutations in the main FH-causing genes including LDLR, APOB, PCSK9 were collected. Variants were classified based on HGVS nomenclature using the mutation database ClinVar. For clinical classification, the Dutch Lipid Clinic Network Score (DLCNS) was used, which is based on off-treatment low-density lipoprotein cholesterol (LDL-C) ranges, family and patient history as well as pathognomonic signs. Results Of 473 patients tested, 102 (21.6%) had a causative mutation (LDLR=84%, APOB=9%, PCSK9=5%), three of which were novel. 14 further, previously unreported variants of unknown significance were identified. The detection rate was 64% in patients with clinically definite FH i.e. DLCNS >8 (10.7% of the cohort), 30% in those with a DLCNS between 6 and 8 (20.6%), 16% in those with a DLCNS between 3 and 5 (47.2%) and 4% in DLCNS |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1093/eurheartj/ehad655.2505 |
| Availability: |
https://doi.org/10.1093/eurheartj/ehad655.2505; https://academic.oup.com/eurheartj/article-pdf/44/Supplement_2/ehad655.2505/53608662/ehad655.2505.pdf |
| Rights: |
https://academic.oup.com/pages/standard-publication-reuse-rights |
| Accession Number: |
edsbas.1FF42D2C |
| Database: |
BASE |