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

Abstract

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 50 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.

• Authors: Pin Yue, Bo Yuan, Daniela S Gerhard, Rosalind J Neuman, William L Isley, William S Harris, Gustav Schonfeld
• Journal: Human mutation (Hum Mutat) Vol. 20 Issue 2 Pg. 110-6 (Aug 2002) ISSN: 1098-1004 [Electronic] United States
• PMID: 12124991 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• Apolipoproteins B
• Genetic Markers

Topics

• Adult
• Aged
• Alternative Splicing (genetics)
• Apolipoproteins B (blood, genetics)
• Chromosome Mapping
• Chromosomes, Human, Pair 2 (genetics)
• Genetic Linkage (genetics)
• Genetic Markers (genetics)
• Humans
• Hypobetalipoproteinemias (blood, genetics)
• Middle Aged
• Mutation (genetics)
• Phenotype
• Polymorphism, Single Nucleotide (genetics)
• Sequence Deletion