Renal amyloidosis caused by a novel stop-codon mutation in the apolipoprotein A-II gene

Masahide Yazaki, Juris J. Liepnieks, Taro Yamashita, Brian Guenther, Martha Skinner, Merrill D. Benson

Research output: Contribution to journalArticle

39 Scopus citations


Background. Although apolipoprotein A-II (apoA-II) associated amyloidosis has been described in the senescent accelerated mouse (SAM) model of aging, so far there has been no report of human apoA-II amyloidosis except for a recent report of renal amyloidosis resulting from a stop-codon to glycine mutation of apoA-II. The mechanisms of amyloid formation in human apoA-II amyloidosis are not clear. Methods. A 46-year-old Caucasian male with proteinuria noted at 42 years of age was studied. Renal biopsy revealed amyloid deposition in glomeruli. DNA analysis of genes known to be associated with hereditary renal amyloidosis revealed no abnormalities. To elucidate the type of his amyloidosis, apoAII gene and plasma apoA-II were examined. Results. DNA analysis revealed heterozygosity for a G to C transversion at the second position of the stop-codon of apoA-II gene, suggesting a stop to serine substitution at codon 78. Western blot analysis and amino acid sequence analysis of the patient's plasma apoA-II showed both normal apoA-II and variant apoA-II with a 21-amino acid residue extension at the C-terminus. Conclusions. These results indicate that the patient's amyloid fibrils were derived from apoA-II and the amyloidogenesis is likely to be closely linked to the peptide extension at the C-terminus of variant apoA-II. The pathogenesis of human apoA-II amyloidosis is different from that of SAM.

Original languageEnglish (US)
Pages (from-to)1658-1665
Number of pages8
JournalKidney international
Issue number5
StatePublished - Nov 2001


  • Amyloid fibril formation
  • Autosomal-dominant disease
  • Glomerulosclerosis
  • Hereditary systemic amyloidosis
  • Lipoprotein
  • Stop-codon mutation

ASJC Scopus subject areas

  • Nephrology

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