DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN

Fatih Ozaltin, Binghua Li, Alysha Rauhauser, Sung Wan An, Oguz Soylemezoglu, Ipek Isik Gonul, Ekim Z. Taskiran, Tulin Ibsirlioglu, Emine Korkmaz, Yelda Bilginer, Ali Duzova, Seza Ozen, Rezan Topaloglu, Nesrin Besbas, Shazia Ashraf, Yong Du, Chaoying Liang, Phylip Chen, Dongmei Lu, Komal VadnagaraSusan Arbuckle, Deborah Lewis, Benjamin Wakeland, Richard J. Quigg, Richard F. Ransom, Edward K. Wakeland, Matthew K. Topham, Nicolas G. Bazan, Chandra Mohan, Friedhelm Hildebrandt, Aysin Bakkaloglu, Chou Long Huang, Massimo Attanasio

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Renal microangiopathies and membranoproliferative GN (MPGN) can manifest similar clinical presentations and histology, suggesting the possibility of a common underlying mechanism in some cases. Here, we performed homozygosity mapping and whole exome sequencing in a Turkish consanguineous family and identified DGKE gene variants as the cause of amembranoproliferative-like glomerularmicroangiopathy. Furthermore, we identified two additional DGKE variants in a cohort of 142 unrelated patients diagnosed with membranoproliferative GN. This gene encodes the diacylglycerol kinase DGK, which is an intracellular lipid kinase that phosphorylates diacylglycerol to phosphatidic acid. Immunofluorescence confocal microscopy demonstrated that mouse and rat Dgk colocalizes with the podocyte marker WT1 but not with the endothelial marker CD31. Patch-clamp experiments in human embryonic kidney (HEK293) cells showed that DGK variants affect the intracellular concentration of diacylglycerol. Taken together, these results not only identify a genetic cause of a glomerular microangiopathy but also suggest that the phosphatidylinositol cycle, which requires DGKE, is critical to the normal function of podocytes.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalJournal of the American Society of Nephrology
Volume24
Issue number3
DOIs
StatePublished - Feb 28 2013

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN'. Together they form a unique fingerprint.

Cite this