Characterization of two novel pathogenic variants at compound heterozygous status in lipase maturation factor 1 gene causing severe hypertriglyceridemia.

BACKGROUND: Severe hypertriglyceridemia is a rare disease characterized by triglyceride levels higher than 1000 mg/dL (11.3 mmol/L) and acute pancreatitis. The disease is caused by pathogenic variants in genes encoding lipoprotein lipase (LPL), apolipoprotein A5, apolipoprotein C2, glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1, and lipase maturation factor 1 (LMF1). OBJECTIVE: We aim to identify the genetic cause of severe hypertriglyceridemia and characterize the new variants in a patient with severe hypertriglyceridemia. METHODS: The proband was a male showing severe hypertriglyceridemia (triglycerides 1416 mg/dL, 16.0 mmol/L); proband's relatives were also screened. Genetic screening included direct sequencing of the above genes and identification of large rearrangements in the LPL gene. Functional characterization of mutant LMF1 variants was performed by complementing LPL maturation in transfected LMF1-deficient mouse fibroblasts. RESULTS: The proband and his affected brother were compound heterozygotes for variants in the LMF1 gene never identified as causative of severe hypertriglyceridemia c.[157delC;1351C>T];[410C>T], p.[(Arg53Glyfs*5)];[(Ser137Leu)]. Functional analysis demonstrated that the p.(Arg53Glyfs*5) truncation completely abolished and the p.(Ser137Leu) missense variant dramatically diminished the lipase maturation activity of LMF1. CONCLUSIONS: In addition to a novel truncating variant, we describe for the first time a missense variant functionally demonstrated affecting the lipase maturation function of LMF1. This is the first case in which compound heterozygous variants in LMF1 were functionally demonstrated as causative of severe hypertriglyceridemia.

Effects of Armolipid Plus on small dense LDL particles in a sample of patients affected by familial combined hyperlipidemia.

AIM: The aim of this study was to test small dense LDL changes with Armolipid Plus treatment in patients with familial combined hyperlipidemia (FCHL). METHODS: After 4 weeks, 30 patients with FCHL were included in an 8-week, randomized, double-blind study and were taking, in addition to the standard diet, either placebo or Armolipid Plus. RESULTS: The placebo group showed no statistically significant differences in the studied parameters; instead, in the Armolipid Plus group, statistically significant reduction differences were detected in BMI (p = 0.010), LDL score (p = 0.035) and an increase in mean LDL particle diameter (p = 0.040). CONCLUSION: The combination of a standard diet with Armolipid Plus is able to reduce LDL score and increase LDL particle diameter in a group of FCHL after 8 weeks of treatment.