A novel missense mutation in the gene for lipoprotein lipase resulting in a highly conservative amino acid substitution (Asp180-->Glu) causes familial chylomicronemia (type I hyperlipoproteinemia).
In Eastern Québec, two major lipoprotein lipase (LPL) gene mutations, P207L and G188E, lead to complete LPL deficiency in homozygote subjects and contribute to elevated predisposition to hypertriglyceridemia in heterozygotes.
To understand the molecular basis of LPL deficiency, two siblings with drastically reduced postheparin plasma lipolytic activities were selected for analysis of their LPL gene.
Such a structure would aid in understanding mutations in LPL that cause familial LPL deficiency in patients and help in the development of therapeutic strategies to target LPL.
Familial chylomicronemia syndrome is a rare disorder of lipoprotein metabolism due to familial lipoprotein lipase (LPL) or apolipoprotein C-II deficiency or the presence of inhibitors to lipoprotein lipase.
The measurement of LPL activity and mass allows identification of the heterozygote state for LPL deficiency, which is characterized by variable expressions of hyperlipidemia and reduced HDL cholesterol.
The purpose of this study was to analyze the physicochemical modifications of plasma lipoproteins produced by LPL activation in two patients with apoC-II deficiency syndrome and by HL activation in two patients with LPL deficiency.
It has previously been estimated that due to genetic "founder effects," 97% of lipoprotein lipase (LPL) gene alleles conferring type I hyperlipoproteinemia (HLP) in French Canadians encode one of the following mutant LPL forms: Gly188-->Glu, Pro207-->Leu, or Asp250-->Asn.
We describe the 2-year follow-up of an open-label trial (CT-AMT-011-01) of AAV1-LPL(S447X) gene therapy for lipoprotein lipase (LPL) deficiency (LPLD), an orphan disease associated with chylomicronemia, severe hypertriglyceridemia, metabolic complications and potentially life-threatening pancreatitis.
Systemic antibody and T cell responses against AAV1 and LPL(S447X), as well as local cellular immune responses in the injected muscle, were investigated in five LPLD subjects.
These results add the Gly188Glu mutation to the growing list of LPL gene mutations underlying familial LPL deficiency in Japanese and indicate that the origin of the Gly188Glu mutation is not necessarily common but would be multicentric at least in part.
Two distinct first-order rates of inactivation were obtained and the derived constants used to calculate the lipoprotein lipase and hepatic lipase contributions to the total post-heparin triglyceride hydrolase activity in normal controls and in patients with familial hyperchylomicronaemia.