Biomaterial Database

A Novel APOC2 Missense Mutation Causing Apolipoprotein C-II Deficiency With Severe Triglyceridemia and Pancreatitis. 2017

Masako Ueda, and Richard L Dunbar, and Anna Wolska, and Tracey U Sikora, and Maria Del Rosario Escobar, and Naomi Seliktar, and Emil deGoma, and Stephanie DerOhannessian, and Linda Morrell, and Adam D McIntyre, and Frances Burke, and Denis Sviridov, and Marcelo Amar, and Robert D Shamburek, and Lita Freeman, and Robert A Hegele, and Alan T Remaley, and Daniel J Rader

Division of Translational Medicine and Human Genetics, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104.

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.

UI	MeSH Term	Description	Entries
D008072	Hyperlipoproteinemia Type I	An inherited condition due to a deficiency of either LIPOPROTEIN LIPASE or APOLIPOPROTEIN C-II (a lipase-activating protein). The lack of lipase activities results in inability to remove CHYLOMICRONS and TRIGLYCERIDES from the blood which has a creamy top layer after standing.	Apolipoprotein C-II Deficiency,Hyperchylomicronemia, Familial,Lipoprotein Lipase Deficiency, Familial,Burger-Grutz Syndrome,C-II Anapolipoproteinemia,Chylomicronemia, Familial,Familial Fat-Induced Hypertriglyceridemia,Familial Hyperchylomicronemia,Familial Hyperlipoproteinemia Type 1,Familial LPL Deficiency,Familial Lipoprotein Lipase Deficiency,Hyperlipemia, Essential Familial,Hyperlipemia, Idiopathic, Burger-Grutz Type,Hyperlipoproteinemia Type Ia,Hyperlipoproteinemia Type Ib,Hyperlipoproteinemia, Type I,Hyperlipoproteinemia, Type Ia,Hyperlipoproteinemia, Type Ib,LIPD Deficiency,Lipase D Deficiency,Lipoprotein Lipase Deficiency,Anapolipoproteinemia, C-II,Anapolipoproteinemias, C-II,Apolipoprotein C II Deficiency,Apolipoprotein C-II Deficiencies,Burger Grutz Syndrome,Burger-Grutz Syndromes,C-II Anapolipoproteinemias,Chylomicronemias, Familial,Deficiencies, Apolipoprotein C-II,Deficiencies, Familial LPL,Deficiencies, LIPD,Deficiencies, Lipase D,Deficiencies, Lipoprotein Lipase,Deficiency, Apolipoprotein C-II,Deficiency, Familial LPL,Deficiency, LIPD,Deficiency, Lipase D,Deficiency, Lipoprotein Lipase,Essential Familial Hyperlipemia,Essential Familial Hyperlipemias,Familial Chylomicronemia,Familial Chylomicronemias,Familial Fat Induced Hypertriglyceridemia,Familial Fat-Induced Hypertriglyceridemias,Familial Hyperchylomicronemias,Familial Hyperlipemia, Essential,Familial Hyperlipemias, Essential,Familial LPL Deficiencies,Fat-Induced Hypertriglyceridemia, Familial,Fat-Induced Hypertriglyceridemias, Familial,Hyperchylomicronemias, Familial,Hyperlipemias, Essential Familial,Hyperlipoproteinemia Type Ias,Hyperlipoproteinemia Type Ibs,Hyperlipoproteinemia Type Is,Hyperlipoproteinemias, Type I,Hyperlipoproteinemias, Type Ia,Hyperlipoproteinemias, Type Ib,Hypertriglyceridemia, Familial Fat-Induced,Hypertriglyceridemias, Familial Fat-Induced,LIPD Deficiencies,LPL Deficiencies, Familial,LPL Deficiency, Familial,Lipase D Deficiencies,Lipase Deficiencies, Lipoprotein,Lipoprotein Lipase Deficiencies,Syndrome, Burger-Grutz,Syndromes, Burger-Grutz,Type I Hyperlipoproteinemia,Type I Hyperlipoproteinemias,Type Ia Hyperlipoproteinemia,Type Ia Hyperlipoproteinemias,Type Ib Hyperlipoproteinemia,Type Ib Hyperlipoproteinemias
D008297	Male		Males
D010195	Pancreatitis	INFLAMMATION of the PANCREAS. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of CHRONIC PANCREATITIS (International Symposium on Acute Pancreatitis, Atlanta, 1992). The two most common forms of acute pancreatitis are ALCOHOLIC PANCREATITIS and gallstone pancreatitis.	Acute Edematous Pancreatitis,Acute Pancreatitis,Pancreatic Parenchyma with Edema,Pancreatic Parenchymal Edema,Pancreatitis, Acute,Pancreatitis, Acute Edematous,Peripancreatic Fat Necrosis,Acute Edematous Pancreatitides,Acute Pancreatitides,Edema, Pancreatic Parenchymal,Edematous Pancreatitides, Acute,Edematous Pancreatitis, Acute,Fat Necrosis, Peripancreatic,Necrosis, Peripancreatic Fat,Pancreatic Parenchymal Edemas,Pancreatitides, Acute,Pancreatitides, Acute Edematous,Parenchymal Edema, Pancreatic,Peripancreatic Fat Necroses
D012008	Recurrence	The return of a sign, symptom, or disease after a remission.	Recrudescence,Relapse,Recrudescences,Recurrences,Relapses
D006720	Homozygote	An individual in which both alleles at a given locus are identical.	Homozygotes
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328	Adult	A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available.	Adults
D015228	Hypertriglyceridemia	A condition of elevated levels of TRIGLYCERIDES in the blood.	Hypertriglyceridemias
D044383	Black People	Persons having origins in any of the black racial groups of AFRICA. Note that OMB category BLACK OR AFRICAN AMERICAN is available for the United States population groups. Race and ethnicity terms, as used in the federal government, are self-identified social construct and may include terms outdated and offensive in MeSH to assist users who are interested in retrieving comprehensive search results for studies such as in longitudinal studies.	African Continental Ancestry Group,Black Person,Negroid Race,Black Peoples,Black Persons,Negroid Races,People, Black,Person, Black,Persons, Black,Race, Negroid
D053304	Apolipoprotein C-II	A 9-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS. It contains a cofactor for LIPOPROTEIN LIPASE and activates several triacylglycerol lipases. The association of Apo C-II with plasma CHYLOMICRONS; VLDL, and HIGH-DENSITY LIPOPROTEINS is reversible and changes rapidly as a function of triglyceride metabolism. Clinically, Apo C-II deficiency is similar to lipoprotein lipase deficiency (HYPERLIPOPROTEINEMIA TYPE I) and is therefore called hyperlipoproteinemia type IB.	Apo C-II,ApoC2,Apolipoprotein C-2,Apolipoprotein CII,Apoprotein C-II,Apo C II,Apolipoprotein C 2,Apolipoprotein C II,Apoprotein C II