A Novel Mutation ApoE2 Kurashiki (R158P) in a Patient with Lipoprotein Glomerulopathy

Abstract

Lipoprotein glomerulopathy (LPG) is a rare glomerulopathy caused by lipoprotein thrombi. In almost all cases of LPG, several apolipoprotein (apo) E mutations were reported. Here, we present a case of LPG caused by a novel mutation that we named ApoE2 Kurashiki, which substitutes arginine with proline at apoE codon 158. ApoE2 polymorphism is well known for its relationship to type hyperlipoproteinemia, and the common apoE2 isoform is encoded by the R158C allele. ApoE2 Kurashiki substitutes at the same codon and cannot be distinguished from common apoE2 by standard apoE genotyping or phenotyping.J Atheroscler Thromb, 2011; 18:536-541.

Thermodynamic and structural destabilization of apoE3 by hereditary mutations associated with the development of lipoprotein glomerulopathy

“…ApoE3 variants R136S, R145C, and K146E that have been linked with the development of type III hyperlipoproteinemia, have much milder repercussions on apoE3 structure and stability, indicating that although any mutation in this region of apoE3 may be detrimental to its structural and thermodynamic integrity, the strong effects described in this study may be the result of the exact amino acid substitution, more specifi cally of the introduction of the "helix-breaker" proline residue in a highly helical segment. Interestingly, the misfolding of the N-terminal domain actually enhances the kinetics of 21,23,38 ) in the pathogenesis of LPG has been previously hypothesized, but how, exactly, the mutations in the apoE protein lead to deposition of lipoproteins in the glomerulus is unknown. The nature of amino acid substitutions in these mutations, in conjunction with the structural properties of the apoE domain where they are located, prompted us to investigate the repercussions of these mutations on the protein structure and stability.…”

“…linked to LPG, namely R145P (apoE Sendai) ( 38 ), R147P (apoE Chicago) ( 23 ), and R158P (apoE Osaka or Kurashiki) ( 20,21 ) and characterized their structural, thermodynamic, and functional integrity. Our fi ndings demonstrate that the mutations induce signifi cant thermodynamic, structural, and aggregation-related perturbations in the molecule of apoE3 that induce unfolding of the N-terminal domain to a more molten-globule-like structure.…”

Apolipoprotein E Mutation and Double Filtration Plasmapheresis Therapy on a New Chinese Patient with Lipoprotein Glomerulopathy

“…A total of 13 apoE mutations associated with LPG have been reported so far [5,6,7]. Many of the apoE mutations occur in the LDL receptor binding site, involving 140-150 amino acids in patients with LPG.…”

Significance of a Novel Apolipoprotein E Variant, ApoE Osaka/Kurashiki, in Lipoprotein Glomerulopathy

“…In this point, we recognize that both reports published in this issue 5,6) are very valuable and propose that the novel variant be called apoE Osaka/Kurashiki.…”

“…In this issue, cases of LPG with the same novel variant, apoE2 (Arg158Pro), are published independently, and the variants are called apoE Osaka and apoE Kurashiki, respectively 5,6) . Patients in both reports were not relatives and the distance between their homes was 130 km, although they might have had remote ancestors in common.…”