2. Academic Validation
  3. DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN

DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN

  • J Am Soc Nephrol. 2013 Feb;24(3):377-84. doi: 10.1681/ASN.2012090903.
Fatih Ozaltin 1,  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 Vadnagara,  Susan 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
Affiliations

Affiliation

  • 1 Department of Pediatric Nephrology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
PMID: 23274426 DOI: 10.1681/ASN.2012090903
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 a membranoproliferative-like glomerular microangiopathy. Furthermore, we identified two additional DGKE variants in a cohort of 142 unrelated patients diagnosed with membranoproliferative GN. This gene encodes the diacylglycerol kinase DGKε, which is an intracellular lipid kinase that phosphorylates diacylglycerol to phosphatidic acid. Immunofluorescence confocal microscopy demonstrated that mouse and rat Dgkε colocalizes with the podocyte marker WT1 but not with the endothelial marker CD31. Patch-clamp experiments in human embryonic kidney (HEK293) cells showed that DGKε 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.

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