DIABETES-MELLITUS IN A NEW KINDRED WITH FAMILIAL HYPOBETALIPOPROTEINEMIA AND AN APOLIPOPROTEIN-B TRUNCATION (APO-B-55)

Familial hypobetalipoproteinemia is an autosomal co-dominant disorder, which in a minority of cases is due to a truncation producing mutatio n in the apoB gene. We have identified an apoB mutation in a 40-year o ld hypobetalipoproteinemic man with Type II diabetes mellitus. Immunob lotting of plasma revealed a major band for apoB-100 and a minor band with estimated size between apoB-52 and apoB-55. The proband's 75-year old father with Type II diabetes and a non-diabetic daughter also pos sessed the truncated protein. Direct sequencing of the amplified fragm ent of genomic DNA revealed a C --> T transition at nt 7692 in exon 26 of the apoB gene. This substitution yielded a premature stop codon at residue 2495 and abolished a BsaI restriction endonuclease site. The identical mutation has been described previously; however, the genotyp es and ancestors of the kindred were different, suggesting that the mu tation may have occurred independently. The majority of apoB-55 was el uted as particles smaller than LDL-sized apoB-100, and floated mostly between the LDL and HDL density range. It is worth noting that despite the presence of Type II diabetes, both the proband and his father hav e very low plasma lipid levels and neither have any clinically manifes t macrovascular complications. (C) 1998 Elsevier Science Ireland Ltd.