Clinical and biochemical features of different molecular etiologies of familial chylomicronemia

Journal of Clinical Lipidology
R A HegeleDaniel Gaudet

Abstract

Familial chylomicronemia syndrome (FCS) is an ultra-rare phenotype that is usually caused by biallelic mutations in the LPL gene encoding lipoprotein lipase, or less often in APOC2, APOA5, LMF1, or GPIHBP1 genes encoding cofactors or interacting proteins. We evaluated baseline phenotypes among FCS participants in a phase 3 randomized placebo-controlled trial of volanesorsen (NCT02211209). Baseline clinical, fasting, and postfat load metabolic markers were assessed. Targeted next-generation DNA sequencing plus custom bioinformatics was used to genotype subjects. Among 52 FCS individuals, 41 had biallelic LPL gene mutations (LPL-FCS patients): 82%, 7%, and 11% were missense, nonsense, and splicing variants, respectively. Eleven individuals had non-LPL-FCS; 2 had mutations in APOA5, 5 in GPIHBP1, and 1 each in LMF1 and APOC2 genes, respectively. Two other individuals were double heterozygotes, each with 1 normal LPL allele. All subjects had extremely high triglycerides (TGs) and chylomicrons, but very low levels of other lipoproteins. Compared with LPL-FCS individuals, non-LPL-FCS individuals were very similar for most traits, but had significantly higher postheparin LPL activity, higher 4-hour postprandial insulin and C-peptide l...Continue Reading

Citations

May 31, 2018·Expert Review of Clinical Pharmacology·Rabia ChaudhryAnthony S Wierzbicki
Feb 1, 2019·Circulation Research·Robert A Hegele, Sotirios Tsimikas
Jan 22, 2019·Current Opinion in Lipidology·Michael A IacoccaRobert A Hegele
Aug 8, 2019·The New England Journal of Medicine·Joseph L WitztumEric Bruckert
Jul 23, 2019·European Heart Journal·Veronica J AlexanderSotirios Tsimikas
Nov 26, 2019·European Heart Journal·Ulrich LaufsRobert A Hegele
Jun 7, 2019·Current Opinion in Cardiology·Anthony S Wierzbicki, Timothy M Reynolds
Jul 11, 2020·European Journal of Clinical Investigation·José RiojaPedro Valdivielso
Jun 23, 2019·Human Molecular Genetics·Annakaisa TirronenSeppo Ylä-Herttuala
Oct 18, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Laura D'ErasmoMarcello Arca
Aug 9, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Robert A Hegele, Jacqueline S Dron
Aug 28, 2020·Current Atherosclerosis Reports·Antonio GalloEric Bruckert
May 12, 2019·Journal of Internal Medicine·Amanda J BerberichRobert A Hegele
Nov 19, 2019·Expert Opinion on Pharmacotherapy·Matilda FlorentinGeorge Liamis
Feb 26, 2020·Current Opinion in Cardiology·Hapizah Md NawawiGerald F Watts
Aug 15, 2020·Frontiers in Endocrinology·Jacqueline S Dron, Robert A Hegele
Sep 15, 2019·Journal of Lipid Research·Jacqueline S DronRobert A Hegele
Oct 5, 2020·Canadian Journal of Diabetes·Amanda J BerberichRobert A Hegele
Nov 23, 2020·The Journal of Clinical Endocrinology and Metabolism·Manon BelhassenPhilippe Moulin
Nov 2, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·María José ArizaPedro Valdivielso
Feb 13, 2021·Journal of Clinical Medicine·Mélanie MaltaisDaniel Gaudet
Nov 17, 2020·Frontiers in Endocrinology·Ronald B Goldberg, Alan Chait
May 14, 2021·Journal of Atherosclerosis and Thrombosis·Hiroaki OkazakiMariko Harada-Shiba
Jun 16, 2021·Atherosclerosis·Ira J GoldbergNada A Abumrad
Jul 16, 2021·Expert Review of Cardiovascular Therapy·Julieta Lazarte, Robert A Hegele
Oct 23, 2021·Endocrine Reviews·Amanda J Berberich, Robert A Hegele

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.