ApoB-54.8, a truncated apolipoprotein found primarily in VLDL, is associated with a nonsense mutation in the apoB gene and hypobetalipoproteinemia.

摘要: A new, large kindred with hypobetalipoproteinemia and a previously undescribed truncated form of apolipoprotein B (apoB) has been identified. The asymptomatic, Caucasian male proband (CK, aged 37 years) total plasma cholesterol, triglyceride, low density lipoprotein-(LDL) high lipoprotein- (HDL) apoB concentrations 108, 131, 32, 50, 16 mg/dl, respectively. Plasma samples 11 family members spanning three generations, which had less than 5th percentile LDL-cholesterol, contained bands detected on immunoblots: the normal apoB-100 apoB-48 an unusual band apparent molecular mass 299,356 +/- 9580 daltons (approximately 54% weight apoB-100). Additional immunoblotting experiments using several different anti-apoB monoclonal antibodies showed that carboxyl terminal deleted somewhere between amino acid residues 2148-2488. segment genomic DNA from was amplified by polymerase chain reaction (PCR) nucleotides 7491-7791 Exon 26 gene. cloned into pGEM3Zf(-) sequenced. C----T transition found at nucleotide 7665, resulting in premature stop codon residue 2486 corresponding to apoB-54.8. These results were confirmed direct sequencing PCR products apoB-54.8 positive negative members. Allele-specific oligonucleotides used identify other affected Cosegregation occurred all cases. Based haplotypes constructed restriction fragment length polymorphism, variable number tandem repeats, 5' insertion/deletion analyses presence or absence apoB-54.8, it possible assign single allele mutation throughout family. In contrast shorter truncations such as apoB-31, apoB-40, apoB-46, are particles HDL range, apoB-89 is primarily LDL, very lipoproteins, much virtually absent HDL. This suggests truncation may significantly affect metabolism associated lipoprotein particles.