TY - JOUR
T1 - Novel type of renal amyloidosis derived from apolipoprotein-CII
AU - Nasr, Samih H.
AU - Dasari, Surendra
AU - Hasadsri, Linda
AU - Theis, Jason D.
AU - Vrana, Julie A.
AU - Gertz, Morie A.
AU - Muppa, Prasuna
AU - Zimmermann, Michael T.
AU - Grogg, Karen L.
AU - Dispenzieri, Angela
AU - Sethi, Sanjeev
AU - Highsmith, W. Edward
AU - Merlini, Giampaolo
AU - Leung, Nelson
AU - Kurtin, Paul J.
N1 - Publisher Copyright:
© 2017 by the American Society of Nephrology.
PY - 2017/2
Y1 - 2017/2
N2 - Amyloidosis is characterized by extracellular deposition of misfolded proteins as insoluble fibrils. Most renal amyloidosis cases are Ig light chain, AA, or leukocyte chemotactic factor 2 amyloidosis, but rare hereditary forms can also involve the kidneys. Here, we describe the case of a 61-year-old woman who presented with nephrotic syndrome and renal impairment. Examination of the renal biopsy specimen revealed amyloidosis with predominant involvement of glomeruli and medullary interstitium. Proteomic analysis of Congo red-positive deposits detected large amounts of the Apo-CII protein. DNA sequencing of the APOC2 gene in the patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. We also detected the mutant peptide in the proband's renal amyloid deposits. Using proteomics, we identified seven additional elderly patients with Apo-CII-rich amyloid deposits, all of whom had kidney involvement and histologically exhibited nodular glomerular involvement. Although prior in vitro studies have shown that Apo-CII can form amyloid fibrils and that certain mutations in this protein promote amyloid fibrillogenesis, there are no reports of this type of amyloidosis in humans.We propose that this study reveals a new form of hereditary amyloidosis (AApoCII) that is derived from the Apo-CII protein and appears tomanifest in the elderly and preferentially affect the kidneys.
AB - Amyloidosis is characterized by extracellular deposition of misfolded proteins as insoluble fibrils. Most renal amyloidosis cases are Ig light chain, AA, or leukocyte chemotactic factor 2 amyloidosis, but rare hereditary forms can also involve the kidneys. Here, we describe the case of a 61-year-old woman who presented with nephrotic syndrome and renal impairment. Examination of the renal biopsy specimen revealed amyloidosis with predominant involvement of glomeruli and medullary interstitium. Proteomic analysis of Congo red-positive deposits detected large amounts of the Apo-CII protein. DNA sequencing of the APOC2 gene in the patient and one of her children detected a heterozygous c.206A→T transition, causing an E69V missense mutation. We also detected the mutant peptide in the proband's renal amyloid deposits. Using proteomics, we identified seven additional elderly patients with Apo-CII-rich amyloid deposits, all of whom had kidney involvement and histologically exhibited nodular glomerular involvement. Although prior in vitro studies have shown that Apo-CII can form amyloid fibrils and that certain mutations in this protein promote amyloid fibrillogenesis, there are no reports of this type of amyloidosis in humans.We propose that this study reveals a new form of hereditary amyloidosis (AApoCII) that is derived from the Apo-CII protein and appears tomanifest in the elderly and preferentially affect the kidneys.
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U2 - 10.1681/ASN.2015111228
DO - 10.1681/ASN.2015111228
M3 - Article
C2 - 27297947
AN - SCOPUS:85016439246
SN - 1046-6673
VL - 28
SP - 439
EP - 445
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 2
ER -