Renal amyloidosis caused by a novel stop-codon mutation in the apolipoprotein A-II gene.
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, apoA-II 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.
Yazaki
M
M
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 975 West Walnut Street, 1B-503, Indianapolis, IN 46202, USA.
Liepnieks
J J
JJ
Yamashita
T
T
Guenther
B
B
Skinner
M
M
Benson
M D
MD
D000595:Amino Acid Sequence; D000686:Amyloidosis / Q000235:genetics*; D016633:Apolipoprotein A-II / Q000235:genetics*; D001483:Base Sequence; D018388:Codon, Terminator; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
D016633:Apolipoprotein A-II; D018388:Codon, Terminator