{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:04:11Z","timestamp":1791335051814,"version":"4.3.1"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JASN"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:p>\n                    The recent discovery of mutations in the gene encoding diacylglycerol kinase\n                    <jats:italic toggle=\"yes\">\u03b5<\/jats:italic>\n                    (DGKE) identified a novel pathophysiologic mechanism leading to HUS and\/or MPGN. We report ten new patients from eight unrelated kindreds with DGKE nephropathy. We combined these cases with all previously published cases to characterize the phenotypic spectrum and outcomes of this new disease entity. Most patients presented with HUS accompanied by proteinuria, whereas a subset of patients exhibited clinical and histologic patterns of MPGN without TMA. We also report the first two patients with clinical and histologic HUS\/MPGN overlap. DGKE-HUS typically manifested in the first year of life but was not exclusively limited to infancy, and viral triggers frequently preceded HUS episodes. We observed signs of complement activation in some patients with DGKE-HUS, but the role of complement activation remains unclear. Most patients developed a slowly progressive proteinuric nephropathy: 80% of patients did not have ESRD within 10 years of diagnosis. Many patients experienced HUS remission without specific treatment, and a few patients experienced HUS recurrence despite complete suppression of the complement pathway. Five patients received renal allografts, with no post-transplant recurrence reported. In conclusion, we did not observe a clear genotype-phenotype correlation in patients with DGKE nephropathy, suggesting additional factors mediating phenotypic heterogeneity. Furthermore, the benefits of anti-complement therapy are questionable but renal transplant may be a feasible option in the treatment of patients with this condition.\n                  <\/jats:p>","DOI":"10.1681\/asn.2017010031","type":"journal-article","created":{"date-parts":[[2017,5,19]],"date-time":"2017-05-19T20:40:24Z","timestamp":1495226424000},"page":"3066-3075","source":"Crossref","is-referenced-by-count":60,"title":["The Phenotypic Spectrum of Nephropathies Associated with Mutations in Diacylglycerol Kinase \u03b5"],"prefix":"10.1681","volume":"28","author":[{"given":"Karolis","family":"Azukaitis","sequence":"first","affiliation":[{"name":"Clinic of Pediatrics, Faculty of Medicine, Vilnius University, Vilnius, Lithuania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Simkova","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Department, Dubai Hospital, Dubai, United Arab Emirates;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Abdul","family":"Majid","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Department, Dubai Hospital, Dubai, United Arab Emirates;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Galiano","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Adolescent Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Benz","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Adolescent Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Amann","sequence":"additional","affiliation":[{"name":"Nephropathology, Institute of Pathology, Friedrich-Alexander University Erlangen-N\u00fcrnberg, Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"Bockmeyer","sequence":"additional","affiliation":[{"name":"Nephropathology, Institute of Pathology, Friedrich-Alexander University Erlangen-N\u00fcrnberg, Erlangen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radha","family":"Gajjar","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin E.","family":"Meyers","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Pediatrics, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae Il","family":"Cheong","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Seoul National University Children\u2019s Hospital, Seoul, Korea;"},{"name":"Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e4rbel","family":"Lange-Sperandio","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Department of Pediatrics, Dr. von Hauner Children\u2019s Hospital, Ludwig-Maximilians University, Munich, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese","family":"Jungraithmayr","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Center, Klinikum Memmingen, Memmingen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00e9ronique","family":"Fr\u00e9meaux-Bacchi","sequence":"additional","affiliation":[{"name":"Department of Immunology, H\u00f4pital Europ\u00e9en Georges-Pompidou, Assistance Publique\u2013H\u00f4pitaux de Paris, Paris, France;"},{"name":"Unit\u00e9 Mixte de Recherche en Sant\u00e9 872, Centre de Recherche des Cordeliers, Paris, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Center for Human Genetics, Bioscientia, Ingelheim, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Bereczki","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Szeged, Szeged, Hungary;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Miklaszewska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Jagiellonian University Medical College, Cracow, Poland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorottya","family":"Csuka","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Research Laboratory and George F\u00fcst Complement Diagnostic Laboratory, Semmelweis University, Budapest, Hungary;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Proh\u00e1szka","sequence":"additional","affiliation":[{"name":"Third Department of Internal Medicine, Research Laboratory and George F\u00fcst Complement Diagnostic Laboratory, Semmelweis University, Budapest, Hungary;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Gipson","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew G.","family":"Sampson","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Pediatrics, University of Michigan School of Medicine, Ann Arbor, Michigan;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathieu","family":"Lemaire","sequence":"additional","affiliation":[{"name":"Program in Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Canada;"},{"name":"Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Canada;"},{"name":"Division of Nephrology, Department of Paediatrics, The Hospital for Sick Children, Toronto, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, Heidelberg University, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,5,19]]},"reference":[{"key":"B1-20230819","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/1750-1172-6-60","article-title":"Atypical hemolytic uremic syndrome.","volume":"6","author":"Loirat","year":"2011","journal-title":"Orphanet J Rare Dis"},{"key":"B2-20230819","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2215\/CJN.02210310","article-title":"Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype.","volume":"5","author":"Noris","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"B3-20230819","doi-asserted-by":"crossref","first-page":"1676","DOI":"10.1056\/NEJMra0902814","article-title":"Atypical hemolytic-uremic syndrome.","volume":"361","author":"Noris","year":"2009","journal-title":"N Engl J Med"},{"key":"B4-20230819","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1182\/asheducation-2011.1.15","article-title":"Atypical hemolytic uremic syndrome, genetic basis, and clinical manifestations.","volume":"2011","author":"Kavanagh","year":"2011","journal-title":"Hematology (Am Soc Hematol Educ Program)"},{"key":"B5-20230819","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/ng.2590","article-title":"Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome.","volume":"45","author":"Lemaire","year":"2013","journal-title":"Nat Genet"},{"key":"B6-20230819","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1182\/blood-2014-06-579953","article-title":"Loss of DGK\u03b5 induces endothelial cell activation and death independently of complement activation.","volume":"125","author":"Bruneau","year":"2015","journal-title":"Blood"},{"key":"B7-20230819","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1681\/ASN.2013080886","article-title":"Phenotypic expansion of DGKE-associated diseases.","volume":"25","author":"Westland","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"B8-20230819","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1160\/TH15-01-0007","article-title":"Atypical haemolytic uraemic syndrome in a Japanese patient with DGKE genetic mutations.","volume":"114","author":"Miyata","year":"2015","journal-title":"Thromb Haemost"},{"key":"B9-20230819","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.2215\/CJN.01640214","article-title":"Complement mutations in diacylglycerol kinase-\u03b5-associated atypical hemolytic uremic syndrome.","volume":"9","author":"S\u00e1nchez Chinchilla","year":"2014","journal-title":"Clin J Am Soc Nephrol"},{"key":"B10-20230819","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.2215\/CJN.08520814","article-title":"Characterization of a new DGKE intronic mutation in genetically unsolved cases of familial atypical hemolytic uremic syndrome.","volume":"10","author":"Mele","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"B11-20230819","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1681\/ASN.2012090903","article-title":"DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN.","volume":"24","author":"Ozaltin","year":"2013","journal-title":"J Am Soc Nephrol"},{"key":"B12-20230819","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1111\/ped.12549","article-title":"Atypical hemolytic uremic syndrome: Korean pediatric series.","volume":"57","author":"Lee","year":"2015","journal-title":"Pediatr Int"},{"key":"B13-20230819","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1101\/gr.3577405","article-title":"Distribution and intensity of constraint in mammalian genomic sequence.","volume":"15","author":"Cooper","year":"2005","journal-title":"Genome Res"},{"key":"B14-20230819","doi-asserted-by":"crossref","first-page":"i54","DOI":"10.1093\/bioinformatics\/btp190","article-title":"Identifying novel constrained elements by exploiting biased substitution patterns.","volume":"25","author":"Garber","year":"2009","journal-title":"Bioinformatics"},{"key":"B15-20230819","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nmeth0410-248","article-title":"A method and server for predicting damaging missense mutations.","volume":"7","author":"Adzhubei","year":"2010","journal-title":"Nat Methods"},{"key":"B16-20230819","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1038\/nprot.2009.86","article-title":"Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithm.","volume":"4","author":"Kumar","year":"2009","journal-title":"Nat Protoc"},{"key":"B17-20230819","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1038\/nmeth0810-575","article-title":"MutationTaster evaluates disease-causing potential of sequence alterations.","volume":"7","author":"Schwarz","year":"2010","journal-title":"Nat Methods"},{"key":"B18-20230819","doi-asserted-by":"crossref","first-page":"e1001025","DOI":"10.1371\/journal.pcbi.1001025","article-title":"Identifying a high fraction of the human genome to be under selective constraint using GERP++.","volume":"6","author":"Davydov","year":"2010","journal-title":"PLOS Comput Biol"},{"key":"B19-20230819","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/nrneph.2014.250","article-title":"Podocyte dysfunction in atypical haemolytic uraemic syndrome.","volume":"11","author":"Noris","year":"2015","journal-title":"Nat Rev Nephrol"},{"key":"B20-20230819","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1097\/MNH.0b013e328365b3fe","article-title":"Managing and preventing atypical hemolytic uremic syndrome recurrence after kidney transplantation.","volume":"22","author":"Noris","year":"2013","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"B21-20230819","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1086\/302938","article-title":"Phenotypes of patients with \u201csimple\u201d Mendelian disorders are complex traits: Thresholds, modifiers, and systems dynamics.","volume":"66","author":"Dipple","year":"2000","journal-title":"Am J Hum Genet"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/00001751-201710000-00027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:29:07Z","timestamp":1786130947000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/00001751-201710000-00027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,19]]},"references-count":21,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2017010031","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727628617.793565318","asserted-by":"object"}]},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,19]]}}}