title: Apolipoprotein C-II deficiency with no rare variant in the APOC2 gene.
abstract: OBJECTIVE
  Familial apolipoprotein C-II (apoC-II) deficiency is a rare autosomal recessive disorder with marked hypertriglyceridemia resulting from impaired activation of lipoprotein lipase. In most cases of apoC-II deficiency, causative mutations have been found in the protein-coding region of APOC2; however, several atypical cases of apoC-II deficiency were reported to have markedly reduced, but detectable levels of plasma apoC-II protein (hereafter referred to as hypoapoC-II), which resulted from decreased promoter activity or improper splicing of apoC-II mRNA due to homozygous mutations in APOC2. Here we aim to dissect the molecular bases of a new case of hypoapoC-II.
  
  
  METHODS
  We performed detailed biochemical/genetic analyses of our new case of hypoapoC-II, manifesting severe hypertriglyceridemia (plasma triglycerides, 3235 mg·dL(-1)) with markedly reduced levels of plasma apoC-II (0.6 mg·dL(-1)).
  
  
  RESULTS
  We took advantage of a monocyte/macrophage culture system to prove that transcription of apoC-II mRNA was decreased in the patient's cells, which is compatible with the reported features of hypoapoC-II. Concomitantly, transcriptional activity of the minigene reporter construct of the patient's APOC2 gene was decreased; however, no rare variant was detected in the patient's APOC2 gene. Fifty single nucleotide variants were detected in the patient's APOC2, but all were common variants (allele frequencies ＞35%) that are supposedly not causative.
  
  
  CONCLUSIONS
  A case of apoC-II deficiency was found that is phenotypically identical to hypoapoC-II but with no causative mutations in APOC2, implying that other genes regulate apoC-II levels. The clinical entity of hypoapoC-II is discussed.
authors.affiliation: Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Takase
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Hayato
authors.initials: H
authors.lastname: Fujita
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.forename: Motohiro
authors.initials: M
authors.lastname: Sekiya
authors.forename: Masaki
authors.initials: M
authors.lastname: Igarashi
authors.forename: Mikio
authors.initials: M
authors.lastname: Takanashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Izumida
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ohta
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Kumagai
authors.forename: Makiko
authors.initials: M
authors.lastname: Nishi
authors.forename: Midori
authors.initials: M
authors.lastname: Kubota
authors.forename: Yukari
authors.initials: Y
authors.lastname: Masuda
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Taira
authors.forename: Sachiko
authors.initials: S
authors.lastname: Okazaki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Iizuka
authors.forename: Naoya
authors.initials: N
authors.lastname: Yahagi
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Yanai
authors.forename: Norio
authors.initials: N
authors.lastname: Tada
authors.forename: Takanari
authors.initials: T
authors.lastname: Gotoda
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Okazaki
mesh_terms: D053304:Apolipoprotein C-II / Q000172:deficiency* / Q000235:genetics*; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000097:blood* / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood
chemical_list: D053304:Apolipoprotein C-II; D012333:RNA, Messenger; D014280:Triglycerides; C548261:LPL protein, human; D008071:Lipoprotein Lipase