123 - Spectrum of genetic variants in patients suffering from Familial chylomicronaemia syndrome and multifactorial chylomicronaemia syndrome. (ID 956)
Abstract
Background and Aims
Familial chylomicronaemia syndrome (FCS) is a rare, inherited, autosomal recessive disorder characterised by impaired clearance of triglyceride (TG)-rich lipoprotein from plasma, leading to severe hypertriglyceridemia and a markedly increased risk of acute pancreatitis. It is due to pathogenic variants in genes involved in metabolism of TG-rich lipoprotein (LPL, APOA5, APOC2, GPIHBP1 and LMF1). High levels of TG are more often due to multifactorial chylomicronaemia syndrome (MCS), due to the combination of predisposing variants in candidate genes with co-morbidities and environmental factors. We aimed to screen 28 unrelated patients with severe hypertriglyceridemia, recruited based on plasma TG>10 mmol/L.
Methods
The coding regions with the flanking intronic regions of candidate genes were analysed. Multiplex ligation-dependent probe amplification was used to search for large rearrangements in the LPL gene. Some patients were reanalysed by NGS with a custom panel of 28 genes involved in lipid metabolism.
Results
Nine patients resulted homozygotes or compound heterozygotes for 2 pathogenic variants. In 7 patients we found only 1 pathogenic/likely pathogenic variant. Rare variants in APOB, ABCG5 and ABCG8 genes were identified by NGS in 4/7 patients with only 1 pathogenic/likely pathogenic variants. One variant in APOB gene were classified as pathogenic while the rare variant found in the remaining gene were classified as variants of uncertain significance.
Conclusions
Our genetic screening revealed that 9 out of 28 patients presented 2 pathogenic variants, classified as FCS patients. The NGS method is useful for genetic diagnosis of FCS/MCS patients since it identifies potential modifying variants.
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