A COMPOUND HETEROZYGOTE FOR LIPOPROTEIN-LIPASE DEFICIENCY, VAL(69)-]LEU AND GLY(188)-]GLU - CORRELATION BETWEEN IN-VITRO LPL ACTIVITY AND CLINICAL EXPRESSION

作者：BRUIN T^*; TUZGOL S; MULDER WJ; VANDENENDE AE; JANSEN H; HAYDEN MR; KASTELEIN JJP

来源：The Journal of Lipid Research, 1994, 35(3): 438-445.

• PANCREATITIS
• MISSENSE MUTATION

We analyzed the molecular defects in the lipoprotein lipase gene of a patient with type I hyperlipidemia suffering from recurrent pancreatitis, indicative for lipoprotein lipase deficiency. Postheparin lipoprotein lipase activity in the patient was decreased by 70%. Direct genomic sequencing revealed compound heterozygosity for two mutations: the well-known Gly(188)-->Glu and a new Val(69)-->Leu substitution. Val(69) is Situated in a conserved hydrophobic region of the lipoprotein lipase protein, and the substitution with leucine gives rise to a 80% decrease in specific catalytic activity, as supported by site-directed mutagenesis experiments, followed by expression in COS-cells. The combination of both defects in the lipoprotein lipase gene was incidently associated with severe clinical expression of disease, and triglyceride levels of more than 30 mmol/l were measured. In our patient, triglyceride levels were usually below 10 mmol/l. We, therefore, postulate that the residual LPL activity in our patient is usually sufficient to keep the triglyceride level within bounds and expression of disease occurred only when conditions such as alcohol abuse or poor compliance to diet were present.

• 出版日期1994-3