Genetic Characteristics of Latvian Patients with Familial Hypercholesterolemia: The First Analysis from Genome-Wide Sequencing

Overview

Journal J Clin Med

Specialty General Medicine

Date 2023 Aug 12

PMID 37568561

Authors

Gustavs Latkovskis

Raimonds Rescenko-Krums

Georgijs Nesterovics

Monta Briviba

Vita Saripo

Dainus Gilis

Elizabete Terauda

Ruta Meiere

Gunda Skudrina

Andrejs Erglis

Joana Rita Chora

Mafalda Bourbon

Janis Klovins

Affiliations

Soon will be listed here.

Abstract

Background: There is limited data on the genetic characteristics of patients with familial hypercholesterolemia (FH) in Latvia. We aim to describe monogenic variants in patients from the Latvian Registry of FH (LRFH).

Methods: Whole genome sequencing with 30× coverage was performed in unrelated index cases from the LRFH and the Genome Database of Latvian Population. , , , , , , , , , and genes were analyzed. Only variants annotated as pathogenic (P) or likely pathogenic (LP) using the FH Variant Curation Expert Panel guidelines for and adaptations for and were reported.

Results: Among 163 patients, the mean highest documented LDL-cholesterol level was 7.47 ± 1.60 mmol/L, and 79.1% of patients had LDL-cholesterol ≥6.50 mmol/L. A total of 15 P/LP variants were found in 34 patients (diagnostic yield: 20.9%): 14 in the gene and 1 in the gene. Additionally, 24, 54, and 13 VUS were detected in and , respectively. No P/LP variants were identified in the other tested genes.

Conclusions: Despite the high clinical likelihood of FH, confirmed P/LP variants were detected in only 20.9% of patients in the Latvian cohort when assessed with genome-wide next generation sequencing.

Citing Articles

Improved Genetic Characterization of Hypercholesterolemia in Latvian Patients with Familial Hypercholesterolemia: A Combined Monogenic and Polygenic Approach Using Whole-Genome Sequencing.

Atava I, Briviba M, Nesterovics G, Saripo V, Gilis D, Meiere R Int J Mol Sci. 2025; 25(24.

PMID: 39769230 PMC: 11677843. DOI: 10.3390/ijms252413466.

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