Journal article
DGKE Variants Cause a Glomerular Microangiopathy That Mimics Membranoproliferative GN
Journal of the American Society of Nephrology, Vol.24(3), pp.377-384
12/28/2012
DOI: 10.1681/ASN.2012090903
PMCID: PMC3582208
PMID: 23274426
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.
Details
- Title: Subtitle
- DGKE Variants Cause a Glomerular Microangiopathy That Mimics Membranoproliferative GN
- Creators
- Fatih Ozaltin - Hacettepe UniversityBinghua Li - The University of Texas at DallasAlysha Rauhauser - The University of Texas at DallasSung-Wan An - The University of Texas at DallasOguz Soylemezoglu - Gazi UniversityIpek Isik Gonul - Gazi UniversityEkim Z. Taskiran - Hacettepe UniversityTulin Ibsirlioglu - Hacettepe UniversityEmine Korkmaz - Hacettepe UniversityYelda Bilginer - Hacettepe UniversityAli Duzova - Hacettepe UniversitySeza Ozen - Hacettepe UniversityRezan Topaloglu - Hacettepe UniversityNesrin Besbas - Hacettepe UniversityShazia Ashraf - University of MichiganYong Du - The University of Texas at DallasChaoying Liang - The University of Texas at DallasPhylip Chen - The Ohio State UniversityDongmei Lu - The University of Texas at DallasKomal Vadnagara - The University of Texas at DallasSusan Arbuckle - Sydney Children’s Hospitals NetworkDeborah Lewis - Sydney Children’s Hospitals NetworkBenjamin Wakeland - The University of Texas at DallasRichard J. Quigg - University of ChicagoRichard F. Ransom - Nationwide Children's HospitalEdward K. Wakeland - The University of Texas at DallasMatthew K. Topham - University of UtahNicolas G. Bazan - Louisiana State UniversityChandra Mohan - The University of Texas at DallasFriedhelm Hildebrandt - Howard Hughes Medical InstituteAysin Bakkaloglu - Hacettepe UniversityChou-Long Huang - The University of Texas at DallasMassimo Attanasio - The University of Texas at Dallas
- Resource Type
- Journal article
- Publication Details
- Journal of the American Society of Nephrology, Vol.24(3), pp.377-384
- DOI
- 10.1681/ASN.2012090903
- PMID
- 23274426
- PMCID
- PMC3582208
- NLM abbreviation
- J Am Soc Nephrol
- ISSN
- 1046-6673
- eISSN
- 1533-3450
- Publisher
- American Society of Nephrology
- Language
- English
- Date published
- 12/28/2012
- Academic Unit
- Nephrology; Internal Medicine
- Record Identifier
- 9984359947602771
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