title: Compound heterozygotes for a novel mutation, apo E1 Nagoya (Arg142Ser) and Apo E2 (Arg158Cys), with severe type III hyperlipoproteinemia and familial hypercholesterolemia.
abstract: OBJECTIVE
  A patient with severe type III hyperlipoproteinemia and familial hypercholesterolemia (FH) was previously reported (Metabolism, 44,1995:460-465). In the current study, the patient's apolipoprotein (apo) E gene was analyzed.
  
  
  METHODS
  An apo E isoform analysis was performed using isoelectric focusing and immunoblotting. In addition, after DNA preparation, a restriction fragment length polymorphism analysis and DNA sequence analysis were performed.
  
  
  RESULTS
  The patient's apo E phenotype was E2/E1, and the genotype was ε2/ε2. The sequence analysis of the patient's DNA revealed a new variant of apo E, which involves a single substitution of one serine (AGC) for one arginine (CGC) at position 142, thereby adding one negatively charged unit to apo E2. Therefore, the patient was compound heterozygous for apo E1 (Arg142Ser) and apo E2 (Arg158Cys).
  
  
  CONCLUSIONS
  A novel mutation, apo E1 Nagoya (Arg142Ser) in a patient with severe type III hyperlipoproteinemia with heterozygous FH was characterized. Since the presence of arginine at the amino acid residue 142 of apo E is considered to play an important role in binding to LDL receptors, the mutation apo E1 Nagoya (Arg142Ser) likely contributed to the expression of severe type III hyperlipoproteinemia in this patient.
authors: Department of Cardio-Renal Medicine and Hypertension, Nagoya City University Graduate School of Medical Sciences.
authors: Nagahiko
authors: N
authors: Sakuma
authors: Takeshi
authors: T
authors: Hibino
authors: Tomoaki
authors: T
authors: Saeki
authors: Takahiro
authors: T
authors: Nagata
authors: Toru
authors: T
authors: Sato
authors: Noriaki
authors: N
authors: Okuda
authors: Akira
authors: A
authors: Matsunaga
authors: Jun
authors: J
authors: Sasaki
mesh_terms: D053329:Apolipoprotein E2 / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000235:genetics* / Q000473:pathology; D006952:Hyperlipoproteinemia Type III / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA
chemical_list: D053329:Apolipoprotein E2; D001057:Apolipoproteins E; C040661:apolipoprotein E1