Hypercholesterolemia, familial, 2 / Hypobetalipoproteinemia
Definition
Mutations in the APOB gene can lead to two opposite clinical pictures. Gain-of-function mutations prevent apolipoprotein B from binding to the LDL receptor, leading to excess LDL accumulation and early coronary artery disease (familial hypercholesterolemia type 2); most cases are heterozygous. Loss-of-function mutations instead lead to production of an abnormally short apolipoprotein B (familial hypobetalipoproteinemia); hepatic triglyceride export decreases, hepatic steatosis may develop, and fat-soluble vitamin deficiencies may occur. In the biallelic form, a much more severe picture emerges, including hepatomegaly, liver fibrosis, atypical retinitis pigmentosa, and neuromuscular findings.
Gene/region examined
APOB - Whole Gene
Method
Sequence analysis
Accepted sample types
EDTA blood, AF, CVS
Inheritance
Both conditions are inherited in an autosomal codominant manner; the phenotype is mild in heterozygotes and severe in the biallelic state, depending on gene dosage.