Devlin_1989_Am.J.Hum.Genet_45_A4

Lipoprotein lipase (LPL) is a crucial enzyme in the hydrolysis of triglyceride-rich lipoproteins liberating free fatty acids for storage or energy production in the cell. Human LPL deficiency is associated with massive hypertriglyceridemia and presents usually in childhood with abdominal pain, pancreatitis and occasionally xanthomata. The LPL gene is 30 kb in size and contains 10 exons. We now report the characterization of some gene mutations underlying lipoprotein lipase deficiency. Patients studied are mainly of Northern European ancestry but include individuals of Indian and Indonesian extraction. Approximately 25% of the patients of European ancestry have a 2 kb direct tandem duplication of in the LPL gene between exon 6 and an Alu element within intron 6. The common duplication event appears in persons of different ancestries in Europe suggesting that the mutation predates the spread of these populations. The second mutation found in a single family consisted of a 6 kb deletion with breakpoints in introns 2 and 5. In order to define point mutations and small DNA rearrangements we have used PCR amplification of each of the exons. Direct sequencing of these PCR products revealed another mutation in a consanguineous patient of Malay extraction. This alteration is a 5 bp insertion in exon 3, leading to an altered reading frame and premature stop codon in exon 4. Analysis of these mutations together with detailed assessment of the protein and its function will provide information on the relationship between the gene structure and the functional domains that it encodes