Apolipoprotein B Arg3500Gln mutation prevalence in children with hypercholesterolemia: A French multicenter study

Background: Familial defective apolipoprotein B-100, a dominantly inherited form of hypercholesterolemia caused by a single Ar-3500Gln mutation, is si lent in childhood but may confer a high risk of cardiovascular disease in a dulthood. The objective was to determine the prevalence of familial defecti ve apolipoprotein B-100 in hypercholesterolemic French children and to prov ide a basis for targeting screening efforts in this population. Methods: One hundred ninety children attending 13 pediatric clinics distrib uted throughout France were included based on the presence of type IIa hype rcholesterolemia with a plasma low-density lipoprotein-cholesterol level of more than 130 mg/dL. The Arg3500Gln mutation was detected in dried blood s pots using a polymerase chain reaction assay combined with enzymatic restri ction. Results: Three hyperlipidemia phenotypes were found: monogenic dominant pur e hypercholesterolemia (n = 117), polygenic hypercholesterolemia (n = 43), and combined hyperlipidemia (n = 11). Three unrelated children were heteroz ygous for the Arg3500Gln mutation; all three had monogenic dominant pure hy percholesterolemia (3/94 families; 3.2%), yielding a prevalence of 1.83% (3 /164) in hypercholesterolemic children, which is similar to prevalences rep orted in European adults. Conclusions: The familial defective apolipoprotein B-100 mutation was commo n (1/31) in children with a phenotype of familial hypercholesterolemia. sup porting screening in this population with the goal of preventing premature cardiovascular events.