Spectrum of mutations of the LPL gene identified in Italy in patients with severe hypertriglyceridemia

Albumin versus solvent/detergent–treated pooled plasma as replacement fluid for long‐term plasma exchange therapy in a patient with primary hypertriglyceridemia and recurrent hyperlipidemic pancreatitis

“…Postheparin LPL mass and activity was undetectable and the molecular analysis of LPL gene allowed the identification of a novel homozygous loss-of-function mutation (IVS2, c.250-1G/C). 14 The same mutation was detected in the heterozygous form in both parents who show a normal lipid profile.…”

“…We report the use of long‐term PEx in a patient with familial chylomicronemia with recurrent episodes of acute pancreatitis and subchronic abdominal pain. The patient is a homozygote carrier of a recently described mutation in the LPL gene leading to postheparin LPL activity and mass below 5%, leading to stable TG levels over 4000 mg/dL on average with the maximum tolerated medical treatment. This extremely low LPL level hampers the possibility of gene therapy aiming to replace the mutated gene, because patients with these very low TG levels are at high risk of developing neutralizing antibody against the protein coded by the corrected copy of the defective LPL gene .…”

“…The patient recovered from acute pancreatitis with medical therapy and a conventional lipid‐lowering treatment (ω‐3‐fatty acids + fenofibrate), and a low‐fat diet was started. Postheparin LPL mass and activity was undetectable and the molecular analysis of LPL gene allowed the identification of a novel homozygous loss‐of‐function mutation (IVS2, c.250‐1G/C) . The same mutation was detected in the heterozygous form in both parents who show a normal lipid profile.…”

Single, short in‐del, and copy number variations detection in monogenic dyslipidemia using a next‐generation sequencing strategy

“…11,12 Genetic determinants in FCS include homozygous or compound heterozygous mutations in the lipoprotein lipase gene (LPL), and/or its cofactors: apolipoprotein (apo) AV (APOA5) and CII (APOC2), glycosylphosphatidylinositol anchored high-density lipoprotein-binding protein 1 (GPIHBP1), and lipase maturation factor 1 (LMF1) genes. [13][14][15][16] These lipid disorders are due to single nucleotide variation (SNV), short insertion/deletion (in-del), or large scale deletion/duplication spanning whole exons known as copy number variation (CNV) on concerned genes. 4,15 Moreover, recent studies have showed the necessity to extend the gene regions to study (hypercholesterolemic mutations in APOB gene regions not explored in FH patients), 17,18 to extend the number of genes considered (such as heterozygous ANGPTL3 mutations carriers exhibiting FHBL phenotype) 19,20 ; and to study complex modulations of phenotype.…”

“…[13][14][15][16] These lipid disorders are due to single nucleotide variation (SNV), short insertion/deletion (in-del), or large scale deletion/duplication spanning whole exons known as copy number variation (CNV) on concerned genes. 4,15 Moreover, recent studies have showed the necessity to extend the gene regions to study (hypercholesterolemic mutations in APOB gene regions not explored in FH patients), 17,18 to extend the number of genes considered (such as heterozygous ANGPTL3 mutations carriers exhibiting FHBL phenotype) 19,20 ; and to study complex modulations of phenotype. 21 As NGS panel approach successfully detected genetic alterations for the diagnosis of FH or HTG, [22][23][24] we tested the clinical applicability of a custom AmpliSeq panel sequenced on the Ion PGM Sequencer for the detection of mutations in the most frequent dyslipidemia-related genes (ANGPTL3, APOA5, APOC2, APOB, GPIHBP1, LDLR, LMF1, LPL, PCSK9).…”