Identification of a novel and heterozygous LMF1 nonsense mutation in an acute pancreatitis patient with severe hypertriglyceridemia, severe obesity and heavy smoking

Abstract

BackgroundHypertriglyceridemia (HTG) is one of the most common etiologies of acute pancreatitis (AP). Variants in five genes involved in the regulation of plasma lipid metabolism, namely LPL, APOA5, APOC2, GPIHBP1 and LMF1, have been frequently reported to cause or predispose to HTG.MethodsA Han Chinese patient with HTG-induced AP was assessed for genetic variants by Sanger sequencing of the entire coding and flanking sequences of the above five genes.ResultsThe patient was a 32-year-old man with severe obesity (Body Mass Index = 35) and heavy smoking (ten cigarettes per day for more than ten years). At the onset of AP, his serum triglyceride concentration was elevated to 1450.52 mg/dL. We sequenced the entire coding and flanking sequences of the LPL, APOC2, APOA5, GBIHBP1 and LMF1 genes in the patient. We found no putative deleterious variants, with the exception of a novel and heterozygous nonsense variant, c.1024C > T (p.Arg342*; rs776584760), in exon 7 of the LMF1 gene.ConclusionsThis is the first time that a heterozygous LMF1 nonsense variant was found in a HTG-AP patient with severe obesity and heavy smoking, highlighting an important interplay between genetic and lifestyle factors in the etiology of HTG.Electronic supplementary materialThe online version of this article (10.1186/s12944-019-1012-9) contains supplementary material, which is available to authorized users.

Identification of a novel LPL nonsense variant and further insights into the complex etiology and expression of hypertriglyceridemia-induced acute pancreatitis

“…This variable clinical expression may be, at least partly, explained by the existence of an established secondary etiological factor, alcohol abuse, in the proband but not in the diseased mother and older sister. Although interplay between primary and secondary etiological factors in causing HTG-AP has been described in the literature [17,18], to our best knowledge, the present study is the first to demonstrate the possible effect of alcohol abuse in modifying the Fig. 4 Functional characterization of the LPL p.Gln118* variant.…”

“…However, in most cases, the cause of HTG is complex [15]. Severe HTG was recently shown to be primarily polygenic [16], and there is increasing appreciation of the interplay between primary and secondary etiological factors in causing severe HTG [17,18]. In this study, we reported a novel LPL nonsense variant in one typical Chinese family with HTG-AP history and discussed insights into the complex etiology of HTG-AP gleaned from the so far reported pathogenic LPL nonsense variants.…”

“…Genomic DNA was extracted from blood by the Gentra Puregene Blood kit (Qiagen, Dusseldorf, Germany) according to the manufacturer's instructions. All exons and exon/intron boundaries of the LPL, APOA5, APOC2, LMF1 and GPIHBP1 genes were analyzed by sanger sequencing [18].…”

Copy number variations primed lncRNAs deregulation contribute to poor prognosis in colorectal cancer

“…C14orf132 (chromosome 14 open reading frame 132) gene is a novel long non-coding RNA (lincRNA) with unknown functions implicated in tumors, and the only investigation elucidated in C14orf132 is concerned with extremely low birth weight [55]. Lipase maturation factor 1 (LMF1) is a profound regulator of plasma lipid metabolism and majority studies mainly focused on mutations of LMF1 determining severe hypertriglyceridemia [56]. Up to now, there is still lacking of evidence about the latent position of LMF1 in tumorigenesis.…”

Current Diagnosis and Management of Primary Chylomicronemia

“…LMF1 is localized to the endoplasmic reticulum and is required for proper synthesis and secretion of LPL and HL. In addition to nonsense mutations that were originally reported, several other mutations, including missense loss-of-function mutations, have been identified in LMF1 [24][25][26][27][28][29] .…”