Type 1 hyperlipoproteinemia due to a novel deletion of exons 3 and 4 in the GPIHBP1 gene

- Type 1 hyperlipoproteinemia is diagnosed in two related sibpairs.
- Homozygosity for a gross deletion in GPIHBP1 explains presence of Type 1 hyperlipoproteinemia.
- No increase in lipoprotein lipase activity in post-heparin plasma in homozygotes.

ObjectivesType 1 hyperlipoproteinemia is an autosomal recessive disorder characterized by severely elevated plasma triglyceride levels, which may lead to abdominal pain and pancreatitis, eruptive xanthomas and failure to thrive. Mutations in the genes encoding lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), lipase maturing factor 1 (LMF1) or glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) have been found to cause Type 1 hyperlipoproteinemia.MethodsTwo sibpairs belonging to two different branches of an extended pedigree were referred for molecular elucidation for their increased plasma triglyceride levels, which untreated were >27 mmol/L. The genes LPL, APOC2, APOA5, LMF1 and GPIHBP1 were analyzed by DNA sequencing.ResultsNo mutations were found in LPL, APOC2, APOA5 or LMF1. No PCR products were obtained for exons 3 and 4 of GPIHBP1 from DNA of the 4 affected subjects. Subsequent long-range PCR revealed that the four affected were homozygous for a deletion comprising exons 3 and 4 of GPIHBP1. No increase in LPL activity was found in post-heparin plasma from the subjects.ConclusionHomozygosity for a deletion of exons 3 and 4 of GPIHBP1 results in Type 1 hyperlipoproteinemia.