title: Familial lipoprotein lipase deficiency: a case of compound heterozygosity of a novel duplication (R44Kfs*4) and a common mutation (N291S) in the lipoprotein lipase gene.
abstract: Familial lipoprotein lipase (LPL) deficiency (FLLD) is a rare autosomal recessive genetic disorder caused by homozygous or compound heterozygous mutations in the LPL gene. FLLD individuals usually express an impaired or non-functional LPL enzyme with low or absent triglyceride (TG) hydrolysis activity causing severe hypertriglyceridaemia. Here we report a case of FLLD in a 29-year-old man, who initially presented with eruptive cutaneous xanthomata, elevated plasma TG concentration but no other co-morbidities. Subsequent genetic testing of the patient revealed compound heterozygosity of a novel duplication (p.R44Kfs*4) leading to a premature stop codon in exon 2 and a known mutation (N291S) in exon 5 of the LPL gene. Further biochemical analysis of the patient's postheparin plasma confirmed a reduction of total lipase activity compared with his heterozygous father carrying the common N291S mutation and to a healthy control. Also the patient showed increased (1.85-fold) activity of hepatic lipase (HL), indicating a functional link between HL and LPL. In summary, we report a case of FLLD caused by compound heterozygosity of a new duplication and a common mutation in the LPL gene, resulting in residual LPL activity. With such mutations, individuals may not receive a diagnosis before classical FLLD symptoms appear later in adulthood. Nevertheless, early diagnosis and lipid-lowering treatment may favour a reduced risk of premature cardiovascular disease or acute pancreatitis in such individuals.
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark. martin.overgaard@ouh.regionsyddanmark.dk
authors.forename: Martin
authors.initials: M
authors.lastname: Overgaard
authors.forename: Claus Lohman
authors.initials: CL
authors.lastname: Brasen
authors.forename: Dea
authors.initials: D
authors.lastname: Svaneby
authors.forename: Søren
authors.initials: S
authors.lastname: Feddersen
authors.forename: Mads
authors.initials: M
authors.lastname: Nybo
mesh_terms: D000328:Adult; D020440:Gene Duplication / Q000235:genetics*; D006580:Genetic Carrier Screening; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000175:diagnosis* / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*
chemical_list: C548261:LPL protein, human; D008071:Lipoprotein Lipase
keywords: DNA & RNA techniques; Genetics; enzymatic methods