The detection of familial defective apolipoprotein B-100 (FDB) in two australian families

Familial Defective Apolipoprotein B-100 (FDB) arises from a point mutation in the apolipoprotein B gene, which results in defective binding of LDL particles to the LDL receptor. This mutation has been found in Austria, the United Kingdom, Denmark, Germany, the United States and Canada, but not in Finland or Japan. The aim of this study was to establish methods for the detection of this mutation and assess its occurrence in the Australian population. Studies were performed on 39 patients in whom familial forms of hypercholesterolaemia were considered likely on the basis of family histories. An allele specific oligonucleotide assay was established using a PCR amplified 345 base pair region spanning nucleotide 10699 of the apolipoprotein gene. Two patients were found to be heterozygous for the FDB mutation. Family studies have revealed additional members with this mutation, in patterns consistent with autosomal co-dominant inheritance. A separate assay monitoring the growth of U937 cells was developed to detect LDL particles with reduced binding to the LDL receptor (these cells depend on exogenous LDL-cholesterol for growth). When incubated with LDL prepared from patients with the FDB mutation, growth was reduced by approximately 50%. The FDB mutation is therefore present in the Australian population and affects LDL particle binding to the LDL receptors. Ongoing studies will determine the extent to which this mutation is responsible for familial forms of hypercholesterolaemia in this country.