Title : Molecular analysis of three known and one novel LPL variants in patients with type I hyperlipoproteinemia - Caddeo_2018_Nutr.Metab.Cardiovasc.Dis_28_158 |
Author(s) : Caddeo A , Mancina RM , Pirazzi C , Russo C , Sasidharan K , Sandstedt J , Maurotti S , Montalcini T , Pujia A , Leren TP , Romeo S , Pingitore P |
Ref : Nutr Metab Cardiovasc Dis , 28 :158 , 2018 |
Abstract :
BACKGROUND AND AIMS: Type I hyperlipoproteinemia, also known as familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disorder caused by variants in LPL, APOC2, APOA5, LMF1 or GPIHBP1 genes. The aim of this study was to identify novel variants in the LPL gene causing lipoprotein lipase deficiency and to understand the molecular mechanisms. METHODS AND RESULTS: A total of 3 individuals with severe hypertriglyceridemia and recurrent pancreatitis were selected from the Lipid Clinic at Sahlgrenska University Hospital and LPL was sequenced. In vitro experiments were performed in human embryonic kidney 293T/17 (HEK293T/17) cells transiently transfected with wild type or mutant LPL plasmids. Cell lysates and media were used to analyze LPL synthesis and secretion. Media were used to measure LPL activity. Patient 1 was compound heterozygous for three known variants: c.337T > C (W113R), c.644G > A (G215E) and c.1211T > G (M404R); patient 2 was heterozygous for the known variant c.658A > C (S220R) while patient 3 was homozygous for a novel variant in the exon 5 c.679G > T (V227F). All the LPL variants identified were loss-of-function variants and resulted in a substantial reduction in the secretion of LPL protein. CONCLUSION: We characterized at the molecular level three known and one novel LPL variants causing type I hyperlipoproteinemia showing that all these variants are pathogenic. |
PubMedSearch : Caddeo_2018_Nutr.Metab.Cardiovasc.Dis_28_158 |
PubMedID: 29288010 |
Gene_locus related to this paper: human-LPL |
Mutation | M404R_human-LPL G215E_human-LPL S220R_human-LPL V227F_human-LPL W113R_human-LPL |
Gene_locus | human-LPL |
Disease | Hyperlipoproteinemia TypeI |
Caddeo A, Mancina RM, Pirazzi C, Russo C, Sasidharan K, Sandstedt J, Maurotti S, Montalcini T, Pujia A, Leren TP, Romeo S, Pingitore P (2018)
Molecular analysis of three known and one novel LPL variants in patients with type I hyperlipoproteinemia
Nutr Metab Cardiovasc Dis
28 :158
Caddeo A, Mancina RM, Pirazzi C, Russo C, Sasidharan K, Sandstedt J, Maurotti S, Montalcini T, Pujia A, Leren TP, Romeo S, Pingitore P (2018)
Nutr Metab Cardiovasc Dis
28 :158