Novel mutations of APOB cause ApoB truncations undetectable in plasma and familial Hypobetalipoproteinemia

Familial hypobetalipoproteinemia (FHBL) is a genetic disorder characterized by low levels of apoB, 100 and LDL cholesterol. Truncation-producing mutations of apoB (chromosome 2) are among several potential causes of FHBL in patients. Ten new families with FHBL linked to chromosome 2 were identified. In Family 8, a 4432delT in exon 26 produces a frame-shift and a premature stop codon predicted to produce a truncated apoB-30.9. Even though this truncation is just 10 amino acid shorter than the well-documented apoB-31, which is readily detectable in plasma, apoB-30.9 is undetectable. Most truncations shorter than apoB-30 are not detectable in plasma. In Family 34, an acceptor splicing mutation at position -1 of exon 14 changes the acceptor splice site AG to AA. Two families (Family 5 0 and 52) had mutations (apoB-9 and apoB-29) reported previously. In Family 98, a novel point mutation in exon 26 (11163T>G) causes a premature stop codon, and produces a truncated apoB.80.5 readily detectable in plasma. Sequencing of the ApoB, gene in families 1, 5, 18, 58, and 59 did not reveal mutations.