Compound but non-linked heterozygous p.W14X and p.L279 V LPL gene mutations in a Chinese patient with long-term severe hypertriglyceridemia and recurrent acute pancreatitis

• Published in: Lipids in health and disease Vol. 17; no. 1; p. 144
• Main Authors: Li, Xiaoyao, Yang, Qi, Shi, Xiaolei, Chen, Weiwei, Pu, Na, Li, Weiqin, Li, Jieshou
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19.06.2018; BioMed Central; BMC
• Subjects: Acute Disease; Acute pancreatitis; Amino Acid Substitution; Asian Continental Ancestry Group; Base Sequence; Complications and side effects; Gene mutation; Genetic aspects; Genetic Predisposition to Disease; Heterozygote; Humans; Hyperlipidemia; Hypertriglyceridemia; Hypertriglyceridemia - complications; Hypertriglyceridemia - diagnosis; Hypertriglyceridemia - genetics; Hypertriglyceridemia - pathology; Lipoprotein lipase; Lipoprotein Lipase - genetics; LPL gene; Male; Middle Aged; Mutation; Pancreatitis; Pancreatitis - complications; Pancreatitis - diagnosis; Pancreatitis - genetics; Pancreatitis - pathology; Physiological aspects; Polymorphism, Single Nucleotide; Risk factors; Sequence Analysis, DNA; China; LPL gene; Lipoprotein lipase; Acute pancreatitis; Mutation; Hypertriglyceridemia
• ISSN: 1476-511X; 1476-511X
• DOI: 10.1186/s12944-018-0789-2

Variants in the lipoprotein lipase (LPL), apolipoprotein C-II (APOC2), apolipoprotein A-V (APOA5), GPIHBP1 and LMF1 genes may cause severe hypertriglyceridemia (HTG), which is now the second-leading aetiology of acute pancreatitis in China. The patient and his family were assessed for gene variants by Sanger sequencing of exons and exon-intron junctions of the LPL, GPIHBP1, APOA5, APOC2, and LMF1 genes. Post-heparin blood was collected for LPL mass and activity detection. The patient had suffered from long-term severe hypertriglyceridemia and recurrent abdominal pain for over 30 years, since age 26, and 3 bouts of acute pancreatitis. Two heterozygous LPL single-nucleotide polymorphisms (SNPs) were compound but dislinked: a single-nucleotide substitution (c.42G > A) resulting in the substitution of tryptophan with a stop codon (p.W14X) in one allele, and a single-nucleotide substitution (c.835C > G) resulting in a leucine-to-valine substitution (p.L279 V) in another allele. Only one SNP, p.L279 V, was detected in his son. Post-heparin LPL activity and mass were also lower in the patient. Two heterozygous LPL SNPs, W14X and L279 V, were newly found to be compound but dislinked, which may cause long-term severe hypertriglyceridemia and recurrent acute pancreatitis.