Journal Article

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

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

2017

Overview

Context: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.Case Description: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.Conclusions: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.We conducted genetic and functional assays from patient with severe hypertriglyceridemia and recurrent pancreatitis and found a novel missense APOC2 variant causing apoC-II deficiency.

• Publisher: Endocrine Society,Oxford University Press
• Subject: Adult / African Continental Ancestry Group / Apolipoprotein C-II - deficiency / Apolipoprotein C-II - genetics / Apolipoproteins / Case Reports / Editor's Choice / Etiology / Hereditary diseases / Homozygote / Humans / Hyperlipoproteinemia Type I - complications / Hyperlipoproteinemia Type I - genetics / Hyperlipoproteinemia Type I - metabolism / Hypertriglyceridemia / Hypertriglyceridemia - etiology / Hypertriglyceridemia - metabolism / Lipase / Lipoprotein lipase / Male / Missense mutation / Molecular modelling / Mutation, Missense / Pancreatitis / Pancreatitis - etiology / Pancreatitis - metabolism / Peptides / Recurrence