A form of familial hypobetalipoproteinaemia not due to a mutation in the apolipoprotein B gene.

Familial hypobetalipoproteinaemia (FHBL) is a dominant disorder of lipoprotein metabolism characterized by levels of apolipoprotein B-carrying lipoproteins (VLDL, IDL and LDL) which are 50% of the normal levels in the heterozygotes and almost absent in the homozygotes. Several reports have recently shown that the underlying defect in FHBL involves different mutations in the apo B gene which lead to reduced levels of apo B mRNA or to the production of truncated forms of apo B having either a lower synthetic rate or a higher catabolic rate than normal apo B. We here present a three-generation family with several FHBL members in which the linkage analysis shows absence of co-segregation between apo B gene alleles and the hypocholesterolaemic phenotype. We conclude that a dominantly transmitted mutation in a gene other than that for apo B is responsible for the low plasma cholesterol levels.