COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness

Saskia F Heeringa, Gil Chernin, Moumita Chaki, Weibin Zhou, Alexis J Sloan, Ziming Ji, Letian X Xie, Leonardo Salviati, Toby W Hurd, Virginia Vega-Warner, Paul D Killen, Yehoash Raphael, Shazia Ashraf, Bugsu Ovunc, Dominik S Schoeb, Heather M McLaughlin, Rannar Airik, Christopher N Vlangos, Rasheed Gbadegesin, Bernward HinkesPawaree Saisawat, Eva Trevisson, Mara Doimo, Alberto Casarin, Vanessa Pertegato, Gianpietro Giorgi, Holger Prokisch, Agnès Rötig, Gudrun Nürnberg, Christian Becker, Su Wang, Fatih Ozaltin, Rezan Topaloglu, Aysin Bakkaloglu, Sevcan A Bakkaloglu, Dominik Müller, Antje Beissert, Sevgi Mir, Afig Berdeli, Seza Varpizen, Martin Zenker, Verena Matejas, Carlos Santos-Ocaña, Placido Navas, Takehiro Kusakabe, Andreas Kispert, Sema Akman, Neveen A Soliman, Stefanie Krick, Peter Mundel, Jochen Reiser, Peter Nürnberg, Catherine F Clarke, Roger C Wiggins, Christian Faul, Friedhelm Hildebrandt

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)2013-24
Number of pages12
JournalJournal of Clinical Investigation
Issue number5
Publication statusPublished - May 2011

Keywords / Materials (for Non-textual outputs)

  • Animals
  • COS Cells
  • Cercopithecus aethiops
  • Child
  • Child, Preschool
  • HeLa Cells
  • Hearing Loss, Sensorineural
  • Homozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins
  • Kidney Glomerulus
  • Laminin
  • Membrane Proteins
  • Mutation
  • Nephrotic Syndrome
  • Phenotype
  • Podocytes
  • Rats
  • Ubiquinone
  • WT1 Proteins
  • Zebrafish


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