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Apolipoprotein B Arg3500Gln mutation prevalence in children with hypercholesterolemia: a French multicenter study
1Department of Pediatric Gastroenterology and Nutrition, Armand-Trousseau Children's Teaching Hospital, Paris, France.
Insights
Familial defective apolipoprotein B-100 (FDB) is common in French children with hypercholesterolemia. Early screening for this genetic condition can help prevent future cardiovascular disease.
Area of Science:
- Genetics
- Cardiology
- Pediatrics
Background:
- Familial defective apolipoprotein B-100 (FDB) is an inherited hypercholesterolemia caused by the Arg3500Gln mutation.
- While often asymptomatic in childhood, FDB significantly increases cardiovascular disease risk in adulthood.
Purpose of the Study:
- To determine the prevalence of FDB in hypercholesterolemic French children.
- To establish a basis for targeted screening strategies in this pediatric population.
Main Methods:
- 190 children with type IIa hypercholesterolemia (LDL-C > 130 mg/dL) were recruited from 13 French pediatric clinics.
- The Arg3500Gln mutation was identified using polymerase chain reaction and enzymatic restriction on dried blood spots.
Main Results:
- The Arg3500Gln mutation was found in three unrelated children, all with monogenic dominant pure hypercholesterolemia.
- This represents a prevalence of 3.2% in families with hypercholesterolemia and 1.83% in hypercholesterolemic children, consistent with European adult data.
Conclusions:
- The FDB mutation is prevalent (1/31) in children presenting with familial hypercholesterolemia.
- Screening for FDB in this population is supported to prevent premature cardiovascular events.
Background:
Familial defective apolipoprotein B-100, a dominantly inherited form of hypercholesterolemia caused by a single Arg3500Gln mutation, is silent in childhood but may confer a high risk of cardiovascular disease in adulthood. The objective was to determine the prevalence of familial defective apolipoprotein B-100 in hypercholesterolemic French children and to provide a basis for targeting screening efforts in this population.
Methods:
One hundred ninety children attending 13 pediatric clinics distributed throughout France were included based on the presence of type IIa hypercholesterolemia with a plasma low-density lipoprotein-cholesterol level of more than 130 mg/dL. The Arg3500Gln mutation was detected in dried blood spots using a polymerase chain reaction assay combined with enzymatic restriction.
Results:
Three hyperlipidemia phenotypes were found: monogenic dominant pure hypercholesterolemia (n = 117), polygenic hypercholesterolemia (n = 43), and combined hyperlipidemia (n = 11). Three unrelated children were heterozygous for the Arg3500Gln mutation; all three had monogenic dominant pure hypercholesterolemia (3/94 families; 3.2%), yielding a prevalence of 1.83% (3/164) in hypercholesterolemic children, which is similar to prevalences reported in European adults.
Conclusions:
The familial defective apolipoprotein B-100 mutation was common (1/31) in children with a phenotype of familial hypercholesterolemia, supporting screening in this population with the goal of preventing premature cardiovascular events.