Genetic Cascade Screening for Familial Hypercholesterolemia

A population-based study suggests a polygenic cause for FH in many mutation-negative patients, which may reduce the need for genetic screening of relatives.

Familial hypercholesterolemia (FH) — a common autosomal-dominant disorder that predisposes to premature coronary artery disease — is thought to be monogenic. Published guidelines recommend cascade screening of FH patients and their relatives for a single causative mutation in three known culprit genes: LDLR, APOB, and PCSK9. However, a substantial proportion of FH patients are mutation-negative.

Hypothesizing that FH phenotypes can result from accumulation of common, small-effect, low-density lipoprotein (LDL)-raising alleles, investigators assembled a sample of FH patients (321 mutation-negative, 319 mutation-positive) from three U.K.-based sources and a comparison group of healthy controls from the U.K. Whitehall II study (LDL levels, 228,…

Reviewing Author

Beat J. Meyer, MD

Disclosures

Leadership positions in professional societiesBern Heart Foundation (President); International Academy of Medicine, Bern, Switzerland (Director)

Beat J. Meyer, MD

Disclosures

Leadership positions in professional societiesBern Heart Foundation (President); International Academy of Medicine, Bern, Switzerland (Director)

Genetic Cascade Screening for Familial Hypercholesterolemia

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Reviewing Author