title: Apolipoprotein C-II Tuzla: a novel large deletion in APOC2 caused by Alu-Alu homologous recombination in an infant with apolipoprotein C-II deficiency.
abstract: BACKGROUND
  Familial apolipoprotein (apo) C-II deficiency is a very rare inherited disorder characterized by chylomicronemia. Since the discovery in 1978, reports on apo C-II deficient patients have been limited and only 13 different mutations in APOC2, a gene encoding apo C-II protein, were identified.
  
  
  OBJECTIVE
  The objective is to investigate the biochemical and genetic features of a 3-month-old Bosniak girl with chylomicronemia whose apo C-II protein was undetectable in her plasma.
  
  
  METHODS
  APOC2, LPL, APOA5, and GPIHBP1 were sequenced. Isoelectrofocusing and immunoblotting of chylomicrons and VLDL fraction from the patient were performed.
  
  
  RESULTS
  Sequence analysis demonstrated a large deletion of 2978 base pairs in APOC2, which encompassed exons 2, 3, and 4. The patient was homozygous for the deletion. The 5' part of the breakpoint was located in an Alu Sx repetitive element in intron 1 of APOC2, whereas the 3' part of the breakpoint was in another Alu Sx between APOC2 and CLPTM1, a gene flanking APOC2. We speculate that the deletion was caused by a homologous recombination between two Alu Sx elements. No mutations were detected in LPL, APOA5, and GPIHBP1. Isoelectrofocusing and immunoblotting confirmed the absence of apo C-II protein.
  
  
  CONCLUSIONS
  We diagnosed the patient as having apo C-II deficiency and designated the novel large deletion as apo C-II Tuzla. This is the first description of apo C-II deficiency caused by Alu-Alu recombination in APOC2.
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan; Department of Endocrinology and Metabolism, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. Electronic address: QFG00550@nifty.com.
authors.forename: Minoru
authors.initials: M
authors.lastname: Okubo
authors.affiliation: Department of Pediatrics, University Clinical Center Tuzla, 75000 Tuzla, Bosnia and Herzegovina.
authors.forename: Alma
authors.initials: A
authors.lastname: Toromanovic
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Tetsu
authors.initials: T
authors.lastname: Ebara
authors.affiliation: Okinaka Memorial Institute for Medical Research, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Murase
mesh_terms: D020087:Alu Elements / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D019295:Computational Biology; D005260:Female; D059765:Homologous Recombination / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000235:genetics*; D015151:Immunoblotting; D007223:Infant; D007525:Isoelectric Focusing; D008071:Lipoprotein Lipase / Q000235:genetics; D018110:Receptors, Lipoprotein / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D053304:Apolipoprotein C-II; D001054:Apolipoproteins A; C523701:GPIHBP1 protein, human; D018110:Receptors, Lipoprotein; C548261:LPL protein, human; D008071:Lipoprotein Lipase
keywords: Alu repetitive element; Apolipoprotein C-II; Chylomicronemia; Homologous recombination; Hypertriglyceridemia; Large deletion