Key result
Targeted sequencing identified a pathogenic variant in 3.6% of premature CAD patients, and cascade screening found the variant in 43.8% (95% CI 34.7-53.4%) of tested first-degree relatives.
Cohort (n=500)
No
Prospective cohort study demonstrates high yield of genetic screening for familial hypercholesterolaemia in Vietnam, identifying at-risk relatives.
Background: Familial hypercholesterolaemia (FH) is a common monogenic cause of premature coronary artery disease (CAD), yet data from South-East Asia are sparse and the yield of family cascade screening has not previously been reported in Vietnam. Methods: In this prospective, single-centre cohort study (March 2023–September 2025), 500 consecutive patients with premature CAD (men < 55 years, women < 60 years) underwent targeted next-generation sequencing of LDLR, APOB and PCSK9, with Sanger confirmation of pathogenic or likely pathogenic (P/LP) variants. First-degree relatives of variant-positive index patients were offered structured counselling and cascade sequencing of the family-specific variant. Results: A P/LP variant was identified in 18 of 500 patients (3.6%; 95% CI 2.1–5.4%); 17 (94.4%) involved LDLR and one APOB. Nine distinct P/LP variants were observed, with several recurrent, consistent with possible founder effects. Two carriers were homozygous, including one with an APOB frameshift attributable to consanguinity. Variant carriers were younger (mean difference −5.6 years, 95% CI −9.2 to −2.0) with higher LDL-cholesterol (median 227.5 vs. 138 mg/dL) and more extensive coronary disease than non-carriers. Cascade screening was completed in 20 of 26 eligible families (77%); among 105 first-degree relatives tested, 46 (43.8%; 95% CI 34.7–53.4%) carried the family-specific variant, most of them young, asymptomatic offspring or siblings. Conclusions: Precise molecular diagnosis in a small number of index patients identified a much larger cohort of at-risk relatives who would otherwise have remained undiagnosed, providing the first Vietnamese evidence that hospital-anchored cascade screening is feasible and high-yielding in a resource-limited setting.
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Hoang et al. (2026) conducted a cohort in Premature coronary artery disease and familial hypercholesterolaemia (n=500). Targeted next-generation sequencing and family cascade screening was evaluated on Identification of pathogenic or likely pathogenic (P/LP) variants in index patients (95% CI 2.1-5.4). Targeted sequencing identified a pathogenic variant in 3.6% of premature CAD patients, and cascade screening found the variant in 43.8% (95% CI 34.7-53.4%) of tested first-degree relatives.
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