@article{53a5617e3ef74eb1b041d402a935a392,
title = "Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin",
abstract = "Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal failure in children1-3. Identification of four genes mutated in NPHP subtypes 1-4 (refs. 4-9) has linked the pathogenesis of NPHP to ciliary functions9. Ten percent of affected individuals have retinitis pigmentosa, constituting the renal-retinal Senior-Loken syndrome (SLSN). Here we identify, by positional cloning, mutations in an evolutionarily conserved gene, IQCB1 (also called NPHP5), as the most frequent cause of SLSN. IQCBI encodes an IQ-domain protein, nephrocystin-5. All individuals with IQCB1 mutations have retinitis pigmentosa. Hence, we examined the interaction of nephrocystin-5 with RPGR (retinitis pigmentosa GTPase regulator), which is expressed in photoreceptor cilia and associated with 10-20% of retinitis pigmentosa. We show that nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells. Our studies emphasize the central role of ciliary dysfunction in the pathogenesis of SLSN.",
author = "Otto, {Edgar A.} and Bart Loeys and Hemant Khanna and Jan Hellemans and Ralf Sudbrak and Shuling Fan and Ulla Muerb and O'Toole, {John F.} and Juliana Helou and Massimo Attanasio and Boris Utsch and Sayer, {John A.} and Concepcion Lillo and David Jimeno and Paul Coucke and {De Paepe}, Anne and Richard Reinhardt and Sven Klages and Motoyuki Tsuda and Isao Kawakami and Takehiro Kusakabe and Heymut Omran and Anita Imm and Melissa Tippens and Raymond, {Pamela A.} and Jo Hill and Phil Beales and Shirley He and Andreas Kispert and Benjamin Margolis and Williams, {David S.} and Anand Swaroop and Friedhelm Hildebrandt",
note = "Funding Information: We thank the affected individuals and their families for participation; R.H. Lyons for large-scale sequencing; M. Petry for technical assistance; and G. Feldhoff, T. Bonzel, H.P. Krohn, C.R. Lincke, H. Ruder, M.J. Schuermann, S. Briese, W. Wuyts, A. Raes, Y. Pirson and C. Dahan for contribution of materials and clinical data from affected individuals. This research was supported by grants from US National Institutes of Health to F.H., to A.S. and to D.S.W.; by grants to A.S. from the Foundation Fighting Blindness and Research to Prevent Blindness; and by grants from the German Research Foundation to H.O. F.H. is a Frederick G.L. Huetwell Professor. A.S. is Harold F. Falls Collegiate Professor and recipient of RPB Senior Scientific Investigator Award. B.M. is an investigator of the Howard Hughes Medical Institute. J. Hellemans is funded by the Institute for the Promotion of Innovation by Science and Technology in Flanders. A.K. is supported by grants from the German Research Foundation.",
year = "2005",
doi = "10.1038/ng1520",
language = "English (US)",
volume = "37",
pages = "282--288",
journal = "Nature genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "3",
}