title: A novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy.
abstract: BACKGROUND
  Lipoprotein glomerulopathy (LPG) is a novel disease characterized by proteinuria, lipoprotein thrombi in glomeruli, and an increased concentration of plasma apolipoprotein (apo) E. Previous studies have shown that a genetic disorder of apo E may be associated with the genesis of this disease.
  
  
  METHODS
  An apo E mutation was analyzed in a 57-year-old Japanese male with LPG and systemic atherosclerotic complications. Apo E phenotypes were analyzed by isoelectric focusing and immunoblotting. Apo E genotypes were determined by restriction fragment isotyping with HhaI. Polymerase chain reaction (PCR) products of apo E coding region exons 3 and 4 were cloned into pT7Blue-T-vector and were sequenced.
  
  
  RESULTS
  A novel apo E mutation was identified in this patient and his family. There was a discrepancy between an apo E phenotype (E1/3) and genotype (E3/3). Sequence analysis showed a 54 bp deletion in exon 4 of the apo E gene, causing the 18-amino acid deletion (Gln 156-Gly 173-->0). This deletion mutation was further confirmed by the detection of a short fragment of PCR-amplified DNA using polyacrylamide gel electrophoresis. The patient was a heterozygote with apo E1, and this mutation was determined to be the structural basis for the apo E1 phenotype. One of two daughters was a heterozygous carrier of apo E1, although she did not have proteinuria or atherosclerotic diseases.
  
  
  CONCLUSIONS
  Apo E1 (Gln 156-Gly 173-->0) is a novel mutation of apo E that may be etiologically related to LPG and to the development of atherosclerosis. The result of this family study suggests that the occurrence of LPG may involve other genetic or environmental factors.
authors.affiliation: Department of Medicine, Tokyo Women's Medical College, Japan. gv2h-knzw@asahi-net.or.jp
authors.forename: M
authors.initials: M
authors.lastname: Ando
authors.forename: J
authors.initials: J
authors.lastname: Sasaki
authors.forename: H
authors.initials: H
authors.lastname: Hua
authors.forename: A
authors.initials: A
authors.lastname: Matsunaga
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: K
authors.initials: K
authors.lastname: Jou
authors.forename: S
authors.initials: S
authors.lastname: Oikawa
authors.forename: T
authors.initials: T
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Nihei
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D001706:Biopsy; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D017353:Gene Deletion; D005920:Glomerular Mesangium / Q000473:pathology; D006801:Humans; D007525:Isoelectric Focusing; D007674:Kidney Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D014057:Tomography, X-Ray Computed
chemical_list: D001057:Apolipoproteins E; D008074:Lipoproteins