title: Association of a novel 3-amino acid deletion mutation of apolipoprotein E (Apo E Tokyo) with lipoprotein glomerulopathy.
abstract: Lipoprotein glomerulopathy (LPG) is a newly recognized renal disease characterized by abnormal lipoprotein deposition in the glomeruli, dysbetalipoproteinemia, and a high level of plasma apolipoprotein (apo) E. We identified a novel apo E mutation in a 56-year-old Japanese male with LPG. Although the plasma cholesterol and triglyceride levels were normal, the levels of intermediate-density lipoprotein cholesterol and apo E were elevated to 13 mg/dl (0.336 mmol/l; 4.2+/-2.9 mg/dl, mean +/- SD, in 12 normolipidemic controls) and 9.2 mg/dl, respectively. Biochemical analysis revealed an unusual apo E phenotype (E1/3). Apo E genotyping using DNA digested by a restriction enzyme (HhaI) identified a 66-bp fragment which was not seen with any of the common alleles. Sequence analysis of the amplified genomic DNA fragments showed a 9-bp deletion in exon 4 of the apo E gene resulting in a 3-amino acid deletion (residues 141-143). This novel mutation involves the region of the apo E molecule known to be critically involved in binding to its receptor, and this may well transform the apo E molecule, an inefficient ligand, to its receptor(s). How this mutations causes glomerular damage remains to be determined.
authors.affiliation: Department of Medicine and Pathology, School of Medicine Keio University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Konishi
authors.forename: T
authors.initials: T
authors.lastname: Saruta
authors.forename: S
authors.initials: S
authors.lastname: Kuramochi
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: Han
authors.forename: A
authors.initials: A
authors.lastname: Matsunaga
authors.forename: J
authors.initials: J
authors.lastname: Sasaki
mesh_terms: D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D001483:Base Sequence; D001706:Biopsy; D002196:Capillaries / Q000473:pathology; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D004252:DNA Mutational Analysis; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics* / Q000473:pathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D017384:Sequence Deletion; D013927:Thrombosis / Q000473:pathology; D014041:Tokyo
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL