論文 - 詳細
| RRC ID | 20943 |
|---|---|
| 著者 | Heeringa SF, Chernin G, Chaki M, Zhou W, Sloan AJ, Ji Z, Xie LX, Salviati L, Hurd TW, Vega-Warner V, Killen PD, Raphael Y, Ashraf S, Ovunc B, Schoeb DS, McLaughlin HM, Airik R, Vlangos CN, Gbadegesin R, Hinkes B, Saisawat P, Trevisson E, Doimo M, Casarin A, Pertegato V, Giorgi G, Prokisch H, Rötig A, Nürnberg G, Becker C, Wang S, Ozaltin F, Topaloglu R, Bakkaloglu A, Bakkaloglu SA, 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 NA, Krick S, Mundel P, Reiser J, Nürnberg P, Clarke CF, Wiggins RC, Faul C, Hildebrandt F. |
| タイトル | COQ6 mutations in human patients produce nephrotic syndrome with sensorineural deafness. |
| ジャーナル | J Clin Invest |
| Abstract |
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. |
| 巻・号 | 121(5) |
| ページ | 2013-24 |
| 公開日 | 2011-5-1 |
| DOI | 10.1172/JCI45693 |
| PII | 45693 |
| PMID | 21540551 |
| PMC | PMC3083770 |
| MeSH | Animals COS Cells Child Child, Preschool Chlorocebus aethiops HeLa Cells Hearing Loss, Sensorineural / complications Hearing Loss, Sensorineural / genetics* Homozygote Humans Infant Infant, Newborn Intracellular Signaling Peptides and Proteins / genetics Kidney Glomerulus / metabolism Laminin / genetics Membrane Proteins / genetics Mutation* Nephrotic Syndrome / complications Nephrotic Syndrome / genetics* Phenotype Podocytes / metabolism Rats Ubiquinone / genetics* WT1 Proteins / genetics Zebrafish |
| IF | 11.864 |
| 引用数 | 213 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| リソース情報 | |
| カタユウレイボヤ・(ニッポンウミシダ) | Wild C. int |