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 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.
Yue
Pin
P
Division of Atherosclerosis, Nutrition and Lipid Research, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Yuan
Bo
B
Gerhard
Daniela S
DS
Neuman
Rosalind J
RJ
Isley
William L
WL
Harris
William S
WS
Schonfeld
Gustav
G
D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D001055:Apolipoproteins B / Q000097:blood* / Q000235:genetics*; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017384:Sequence Deletion
D001055:Apolipoproteins B; D005819:Genetic Markers