title: Familial lipoprotein lipase deficiency caused by known (G188E) and novel (W394X) LPL gene mutations.
abstract: Lipoprotein lipase (LPL) is the key enzyme in the catabolism of triglyceride-rich lipoproteins in the circulation. Familial LPL deficiency is characterized by hypertriglyceridaemia and absence of LPL activity. We report a case of LPL deficiency in a 43-year-old woman, who initially presented in childhood with chylomicronaemia syndrome. At that time, her plasma triglyceride concentration was approximately 30 mmol/L and post-heparin lipolytic activity was very low. In addition to having the known missense mutation LPL G188E, the patient was also found to have a novel nonsense mutation in exon 8, namely LPL W394X. The novel substitution in exon 8 (c.1262G > A) predicts a truncated protein product of 393 amino acids that lacks the carboxylterminal 12% of the mature LPL. Trp(394) is part of a cluster of exposed tryptophan residues in the carboxyl-terminal domain of LPL important for binding lipid substrate. Of 11 members from her three-generation family, three were heterozygotes for G188E (mean plasma triglyceride, 3.5 +/- 2.0 mmol/L), whereas six were heterozygotes for W394X (triglyceride, 4.3 +/- 1.8 mmol/L). In summary, we describe a case of familial LPL deficiency caused by compound heterozygosity for known (G188E) and novel (W394X) LPL gene mutations.
authors.affiliation: Department of Core Clinical Pathology and Biochemistry, PathWest Laboratory Medicine W/A, Royal Perth Hospital, Perth, WA 6847, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: Hooper
authors.forename: G M
authors.initials: GM
authors.lastname: Crawford
authors.forename: J M
authors.initials: JM
authors.lastname: Brisbane
authors.forename: K
authors.initials: K
authors.lastname: Robertson
authors.forename: G F
authors.initials: GF
authors.lastname: Watts
authors.forename: F M
authors.initials: FM
authors.lastname: van Bockxmeer
authors.forename: J R
authors.initials: JR
authors.lastname: Burnett
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000235:genetics; D002648:Child; D005260:Female; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000097:blood / Q000201:enzymology* / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree
chemical_list: D000596:Amino Acids; D008071:Lipoprotein Lipase