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Heeringa, S.F.* ; Chernin, G.* ; Chaki, M.* ; Zhou, W.* ; Sloan, A.J.* ; Ji, Z.* ; Xie, L.X.* ; Salviati, L.* ; Hurd, T.W.* ; Vega-Warner, V.* ; Killen, P.D.* ; Raphael, Y.* ; Ashraf, S.* ; Ovunc, B.* ; Schoeb, D.S.* ; McLaughlin, H.M.* ; Airik, R.* ; Vlangos, C.N.* ; Gbadegesin, R.* ; Hinkes, B.* ; Saisawat, P.* ; Trevisson, E.* ; Doimo, M.* ; Casarin, A.* ; Pertegato, V.* ; Giorgi, G.* ; Prokisch, H. ; Rotig, A.* ; Nurnberg, G.* ; Becker, C.* ; Wang, S.* ; Ozaltin, F.* ; Topaloglu, R.* ; Bakkaloglu, A.* ; Bakkaloglu, S.A.* ; Müller, D.* ; Beissert, A.* ; Mir, S.* ; Berdeli, A.* ; Varpizen, S.* ; Zenker, M.* ; Matejas, V.* ; Santos-Ocaña, C.* ; Navas, P.* ; Kusakabe, T.* ; Kispert, A.* ; Akman, S.* ; Soliman, N.A.* ; Krick, S.* ; Mundel, P.* ; Reiser, J.* ; Nürnberg, P.* ; Clarke, C.F.* ; Wiggins, R.C.* ; Faul, C.* ; Hildebrandt, F.*

COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness.

J. Clin. Invest. 121, 2013-2024 (2011)
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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 Q10 treatment. In rats, COQ6 was located within cell processes and the Golgi apparatus of renal glomerular podocytes and in stria vascularis cells of the inner ear, consistent with an oto-renal disease phenotype. These data suggest that coenzyme Q10-related forms of SRNS and hearing loss can be molecularly identified and potentially treated.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Coenzyme-Q biosynthesis; Focal segmental glomerulosclerosis; Diphosphate synthase subunit-2; Saccaromyces-cerevisiae; Ubiquinone biosynthesis; COQ(10) deficiency; Glomerular protein; Oxidative stress; Gene; NPHS2
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Journal Journal of Clinical Investigation
Quellenangaben Volume: 121, Issue: 5, Pages: 2013-2024 Article Number: , Supplement: ,
Publisher American Society of Clinical Investigation
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s) Genetics and Epidemiology
PSP Element(s) G-500700-001
PubMed ID 21540551
DOI 10.1172/JCI45693
WOS ID WOS:000290246800035
Scopus ID 79955520308
Erfassungsdatum 2011-09-14
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