{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:04:16Z","timestamp":1786133056557,"version":"build-2736575974"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,2]]},"abstract":"<jats:p>\n                    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\u2013positive 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\u2192T transition, causing an E69V missense mutation. We also detected the mutant peptide in the proband\u2019s renal amyloid deposits. Using proteomics, we identified seven additional elderly patients with Apo-CII\u2013rich amyloid deposits, all of whom had kidney involvement and histologically exhibited nodular glomerular involvement. Although prior\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    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 to manifest in the elderly and preferentially affect the kidneys.\n                  <\/jats:p>","DOI":"10.1681\/asn.2015111228","type":"journal-article","created":{"date-parts":[[2016,6,13]],"date-time":"2016-06-13T23:05:35Z","timestamp":1465859135000},"page":"439-445","source":"Crossref","is-referenced-by-count":60,"title":["Novel Type of Renal Amyloidosis Derived from Apolipoprotein-CII"],"prefix":"10.1681","volume":"28","author":[{"given":"Samih H.","family":"Nasr","sequence":"first","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surendra","family":"Dasari","sequence":"additional","affiliation":[{"name":"Health Sciences Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Hasadsri","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason D.","family":"Theis","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Vrana","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morie A.","family":"Gertz","sequence":"additional","affiliation":[{"name":"Internal Medicine, Mayo Clinic, Rochester, Minnesota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasuna","family":"Muppa","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Health Sciences Research, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Grogg","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Dispenzieri","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"},{"name":"Internal Medicine, Mayo Clinic, Rochester, Minnesota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjeev","family":"Sethi","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Edward","family":"Highsmith","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giampaolo","family":"Merlini","sequence":"additional","affiliation":[{"name":"Istituto di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo and Department of Molecular Medicine, University of Pavia, Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Leung","sequence":"additional","affiliation":[{"name":"Internal Medicine, Mayo Clinic, Rochester, Minnesota; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Kurtin","sequence":"additional","affiliation":[{"name":"Laboratory Medicine and Pathology,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2016,6,13]]},"reference":[{"key":"B1-20231016","doi-asserted-by":"crossref","first-page":"221","DOI":"10.3109\/13506129.2014.964858","article-title":"Nomenclature 2014: Amyloid fibril proteins and clinical classification of the amyloidosis.","volume":"21","author":"Sipe","year":"2014","journal-title":"Amyloid"},{"key":"B2-20231016","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1080\/13506120400000772","article-title":"Mutant fibrinogen A-alpha-chain associated with hereditary renal amyloidosis and peripheral neuropathy.","volume":"11","author":"de Carvalho","year":"2004","journal-title":"Amyloid"},{"key":"B3-20231016","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1080\/13506120410001682578","article-title":"Familial amyloidotic polyneuropathy with severe renal involvement in association with transthyretin Gly47Glu in Dutch, British and American-Finnish families.","volume":"11","author":"Haagsma","year":"2004","journal-title":"Amyloid"},{"key":"B4-20231016","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3109\/13506129.2014.973105","article-title":"Clinical characteristics and SAP scintigraphic findings in 10 patients with AGel amyloidosis.","volume":"21","author":"Rowczenio","year":"2014","journal-title":"Amyloid"},{"key":"B5-20231016","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1111\/j.1365-2796.2011.02470.x","article-title":"Hereditary lysozyme amyloidosis -- phenotypic heterogeneity and the role of solid organ transplantation.","volume":"272","author":"Sattianayagam","year":"2012","journal-title":"J Intern Med"},{"key":"B6-20231016","first-page":"149","article-title":"Familial nephropathic systemic amyloidosis caused by apolipoprotein AI variant Arg26.","volume":"87","author":"Vigushin","year":"1994","journal-title":"Q J Med"},{"key":"B7-20231016","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1046\/j.1523-1755.2003.00047.x","article-title":"Hereditary systemic amyloidosis associated with a new apolipoprotein AII stop codon mutation Stop78Arg.","volume":"64","author":"Yazaki","year":"2003","journal-title":"Kidney Int"},{"key":"B8-20231016","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/ki.2011.316","article-title":"Medullary amyloidosis associated with apolipoprotein A-IV deposition.","volume":"81","author":"Sethi","year":"2012","journal-title":"Kidney Int"},{"key":"B9-20231016","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.2215\/CJN.10491012","article-title":"Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases.","volume":"8","author":"Said","year":"2013","journal-title":"Clin J Am Soc Nephrol"},{"key":"B10-20231016","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.3324\/haematol.2013.102764","article-title":"Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics.","volume":"99","author":"Vrana","year":"2014","journal-title":"Haematologica"},{"key":"B11-20231016","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1021\/pr4011475","article-title":"Clinical proteome informatics workbench detects pathogenic mutations in hereditary amyloidoses.","volume":"13","author":"Dasari","year":"2014","journal-title":"J Proteome Res"},{"key":"B12-20231016","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1016\/j.humpath.2007.04.013","article-title":"Clinical and histological characteristics of renal AA amyloidosis: a retrospective study of 68 cases with a special interest to amyloid-associated inflammatory response.","volume":"38","author":"Verine","year":"2007","journal-title":"Hum Pathol"},{"key":"B13-20231016","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1073\/pnas.74.11.4848","article-title":"Activation of lipoprotein lipase by native and synthetic fragments of human plasma apolipoprotein C-II.","volume":"74","author":"Kinnunen","year":"1977","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B14-20231016","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1172\/JCI112332","article-title":"Apolipoprotein C-II deficiency syndrome. Clinical features, lipoprotein characterization, lipase activity, and correction of hypertriglyceridemia after apolipoprotein C-II administration in two affected patients.","volume":"77","author":"Baggio","year":"1986","journal-title":"J Clin Invest"},{"key":"B15-20231016","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1056\/NEJM197806082982301","article-title":"Hypertriglyceridemia associated with deficiency of apolipoprotein C-II.","volume":"298","author":"Breckenridge","year":"1978","journal-title":"N Engl J Med"},{"key":"B16-20231016","doi-asserted-by":"crossref","first-page":"8276","DOI":"10.1021\/bi000002w","article-title":"Human apolipoprotein C-II forms twisted amyloid ribbons and closed loops.","volume":"39","author":"Hatters","year":"2000","journal-title":"Biochemistry"},{"key":"B17-20231016","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.jmb.2010.04.042","article-title":"Phospholipids enhance nucleation but not elongation of apolipoprotein C-II amyloid fibrils.","volume":"399","author":"Ryan","year":"2010","journal-title":"J Mol Biol"},{"key":"B18-20231016","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1111\/j.1742-4658.2010.07571.x","article-title":"Amyloid oligomers: spectroscopic characterization of amyloidogenic protein states.","volume":"277","author":"Lindgren","year":"2010","journal-title":"FEBS J"},{"key":"B19-20231016","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.jmb.2010.12.006","article-title":"A structural model for apolipoprotein C-II amyloid fibrils: experimental characterization and molecular dynamics simulations.","volume":"405","author":"Teoh","year":"2011","journal-title":"J Mol Biol"},{"key":"B20-20231016","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-3-319-17344-3_7","article-title":"The Role of Lipid in Misfolding and Amyloid Fibril Formation by Apolipoprotein C-II.","volume":"855","author":"Ryan","year":"2015","journal-title":"Adv Exp Med Biol"},{"key":"B21-20231016","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.bpc.2007.08.002","article-title":"Molecular dynamics simulations of a fibrillogenic peptide derived from apolipoprotein C-II.","volume":"130","author":"Legge","year":"2007","journal-title":"Biophys Chem"},{"key":"B22-20231016","doi-asserted-by":"crossref","first-page":"14762","DOI":"10.1039\/c0cp00299b","article-title":"Effects of mutation on the amyloidogenic propensity of apolipoprotein C-II(60-70) peptide.","volume":"12","author":"Todorova","year":"2010","journal-title":"Phys Chem Chem Phys"},{"key":"B23-20231016","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.1021\/acs.biochem.5b00535","article-title":"Hydrogen\/Deuterium Exchange and Molecular Dynamics Analysis of Amyloid Fibrils Formed by a D69K Charge-Pair Mutant of Human Apolipoprotein C-II.","volume":"54","author":"Mao","year":"2015","journal-title":"Biochemistry"},{"key":"B24-20231016","doi-asserted-by":"crossref","first-page":"4957","DOI":"10.1182\/blood-2009-07-230722","article-title":"Classification of amyloidosis by laser microdissection and mass spectrometry-based proteomic analysis in clinical biopsy specimens.","volume":"114","author":"Vrana","year":"2009","journal-title":"Blood"},{"key":"B25-20231016","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1002\/jms.3264","article-title":"Shotgun-proteomics-based clinical testing for diagnosis and classification of amyloidosis.","volume":"48","author":"Theis","year":"2013","journal-title":"J Mass Spectrom"},{"key":"B26-20231016","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/jcc.20289","article-title":"Scalable molecular dynamics with NAMD.","volume":"26","author":"Phillips","year":"2005","journal-title":"J Comput Chem"},{"key":"B27-20231016","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/jcc.20065","article-title":"Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations.","volume":"25","author":"Mackerell","year":"2004","journal-title":"J Comput Chem"},{"key":"B28-20231016","doi-asserted-by":"crossref","first-page":"8084","DOI":"10.1021\/bi049817l","article-title":"The structure and interactions of human apolipoprotein C-II in dodecyl phosphocholine.","volume":"43","author":"MacRaild","year":"2004","journal-title":"Biochemistry"},{"key":"B29-20231016","doi-asserted-by":"crossref","first-page":"2695","DOI":"10.1093\/bioinformatics\/btl461","article-title":"Bio3d: an R package for the comparative analysis of protein structures.","volume":"22","author":"Grant","year":"2006","journal-title":"Bioinformatics"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201702000-00010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:28:01Z","timestamp":1786130881000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201702000-00010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,13]]},"references-count":29,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2015111228","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,13]]}}}