biostudies-literatureHeeringa SFTelethonNIDDK NIH HHSEuropean Commission FP7NIGMS NIH HHS2013-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC3083770biostudies-literatureUnknown121(5)Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of end-stage renal failure. Identification of single-gene causes of SRNS has generated some insights into its pathogenesis; however, additional genes and disease mechanisms remain obscure, and SRNS continues to be treatment refractory. Here we have identified 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping. Each mutation was linked to early-onset SRNS with sensorineural deafness. The deleterious effects of these human COQ6 mutations were validated by their lack of complementation in coq6-deficient yeast. Furthermore, knockdown of Coq6 in podocyte cell lines and coq6 in zebrafish embryos caused apoptosis that was partially reversed by coenzyme QThe Journal of clinical investigationCOQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness.PMC3083770R56 DK046073DK076683R01 DK076683R01 DK046073R01 DK091218R01 GM045952GGP09207P30 DK081943RC1 DK086542R01 DK062472DK086542P30 DK081943GM45952DK46073FP7_201590Soliman NAHildebrandt FHeeringa SFMir SCasarin AProkisch HClarke CFWang SXie LXKillen PDMcLaughlin HMTrevisson EZenker MSchoeb DSGiorgi GKusakabe TVega-Warner VRaphael YKrick SSloan AJSaisawat PMuller DAkman SVlangos CNNavas POzaltin FWiggins RCChaki MChernin GBakkaloglu SARotig AMundel PBakkaloglu ANurnberg PFaul CNurnberg GMatejas VPertegato VDoimo MHinkes BBerdeli ASalviati LAirik ROvunc BZhou WAshraf SReiser JKispert AHurd TWJi ZBeissert AVarpizen SSantos-Ocana CGbadegesin RBecker CTopaloglu RfalseCOQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness.Steroid-resistant nephrotic syndrome (SRNS) is a frequent cause of end-stage renal failure. Identification of single-gene causes of SRNS has generated some insights into its pathogenesis; however, additional genes and disease mechanisms remain obscure, and SRNS continues to be treatment refractory. Here we have identified 6 different mutations in coenzyme Q10 biosynthesis monooxygenase 6 (COQ6) in 13 individuals from 7 families by homozygosity mapping. Each mutation was linked to early-onset SRNS with sensorineural deafness. The deleterious effects of these human COQ6 mutations were validated by their lack of complementation in coq6-deficient yeast. Furthermore, knockdown of Coq6 in podocyte cell lines and coq6 in zebrafish embryos caused apoptosis that was partially reversed by coenzyme Q2011-01-01T00:00:00Z2011 May2025-04-04T21:57:31.974Z2019-03-27T00:41:01ZS-EPMC30837702154055110.1172/jci4569310.1172/JCI45693