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

M. Yazaki, J. J. Liepnieks, T. Yamashita, B. Guenther, M. Skinner, Merrill Benson

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

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
Pages (from-to)1658-1665
Number of pages8
JournalKidney International
Volume60
Issue number5
DOIs
StatePublished - 2001

Fingerprint

Apolipoprotein A-II
Terminator Codon
Amyloidosis
Kidney
Mutation
Genes
Amyloid
Familial Amyloidosis
DNA
Protein Sequence Analysis
Proteinuria
Codon
Glycine
Serine
Western Blotting
Biopsy
Amino Acids

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Renal amyloidosis caused by a novel stop-codon mutation in the apolipoprotein A-II gene. / Yazaki, M.; Liepnieks, J. J.; Yamashita, T.; Guenther, B.; Skinner, M.; Benson, Merrill.

In: Kidney International, Vol. 60, No. 5, 2001, p. 1658-1665.

Research output: Contribution to journalArticle

Yazaki, M. ; Liepnieks, J. J. ; Yamashita, T. ; Guenther, B. ; Skinner, M. ; Benson, Merrill. / Renal amyloidosis caused by a novel stop-codon mutation in the apolipoprotein A-II gene. In: Kidney International. 2001 ; Vol. 60, No. 5. pp. 1658-1665.
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AB - 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.

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