title: A Novel APOC2 Missense Mutation Causing Apolipoprotein C-II Deficiency With Severe Triglyceridemia and Pancreatitis.
abstract: Familial chylomicronemia syndrome (FCS) is a rare heritable disorder associated with severe hypertriglyceridemia and recurrent pancreatitis. Lipoprotein lipase deficiency and apolipoprotein C-II deficiency are two well-characterized autosomal recessive causes of FCS, and three other genes have been described to cause FCS. Because therapeutic approaches can vary according to the underlying etiology, it is important to establish the molecular etiology of FCS.
  
  
  
  A man originally from North Africa was referred to the University of Pennsylvania Lipid Clinic for severe hypertriglyceridemia and recurrent pancreatitis, consistent with the clinical diagnosis of FCS. Molecular analyses of FCS-associated genes revealed a homozygous missense variant R72T in APOC2. Molecular modeling of the variant predicted that the apolipoprotein C-II R72T peptide has reduced lipid binding affinity. In vitro studies of the patient's plasma confirmed the lack of functional apoC-II activity. Moreover, the apoC-II protein was undetectable in the patient's plasma, quantitatively as well as qualitatively.
  
  
  
  We identified a missense APOC2 variant causing apoC-II deficiency in a patient with severe hypertriglyceridemia and recurrent pancreatitis. Beyond dietary management and usual pharmacologic therapies, an apoC-II mimetic peptide may become an optional therapy in patients with apoC-II deficiency in the future.
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Masako
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Dunbar
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894.
authors.forename: Anna
authors.initials: A
authors.lastname: Wolska
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Tracey U
authors.initials: TU
authors.lastname: Sikora
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Maria Del Rosario
authors.initials: MDR
authors.lastname: Escobar
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Naomi
authors.initials: N
authors.lastname: Seliktar
authors.affiliation: Akebia Therapeutics, Cambridge, Massachusetts 02142.
authors.forename: Emil
authors.initials: E
authors.lastname: deGoma
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Stephanie
authors.initials: S
authors.lastname: DerOhannessian
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Linda
authors.initials: L
authors.lastname: Morrell
authors.affiliation: Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, Western University, London, Ontario N6A 5B7, Canada.
authors.forename: Adam D
authors.initials: AD
authors.lastname: McIntyre
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Frances
authors.initials: F
authors.lastname: Burke
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894.
authors.forename: Denis
authors.initials: D
authors.lastname: Sviridov
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Amar
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Shamburek
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894.
authors.forename: Lita
authors.initials: L
authors.lastname: Freeman
authors.affiliation: Blackburn Cardiovascular Genetics Laboratory, Robarts Research Institute, Western University, London, Ontario N6A 5B7, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20894.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
mesh_terms: D000328:Adult; D053304:Apolipoprotein C-II / Q000172:deficiency / Q000235:genetics*; D044383:Black People; D006720:Homozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000209:etiology / Q000378:metabolism*; D008297:Male; D020125:Mutation, Missense; D010195:Pancreatitis / Q000209:etiology / Q000378:metabolism*; D012008:Recurrence
chemical_list: D053304:Apolipoprotein C-II