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Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.

Authors: Arts, HH  Doherty, D  Van Beersum, SE  Parisi, MA  Letteboer, SJ  Gorden, NT  Peters, TA  Marker, T  Voesenek, K  Kartono, A  Ozyurek, H  Farin, FM  Kroes, HY  Wolfrum, U  Brunner, HG  Cremers, FP  Glass, IA  Knoers, NV  Roepman, R 
Citation: Arts HH, etal., Nat Genet. 2007 Jul;39(7):882-8. Epub 2007 Jun 10.
Pubmed: (View Article at PubMed) PMID:17558407
DOI: Full-text: DOI:10.1038/ng2069

Protein-protein interaction analyses have uncovered a ciliary and basal body protein network that, when disrupted, can result in nephronophthisis (NPHP), Leber congenital amaurosis, Senior-Loken syndrome (SLSN) or Joubert syndrome (JBTS). However, details of the molecular mechanisms underlying these disorders remain poorly understood. RPGRIP1-like protein (RPGRIP1L) is a homolog of RPGRIP1 (RPGR-interacting protein 1), a ciliary protein defective in Leber congenital amaurosis. We show that RPGRIP1L interacts with nephrocystin-4 and that mutations in the gene encoding nephrocystin-4 (NPHP4) that are known to cause SLSN disrupt this interaction. RPGRIP1L is ubiquitously expressed, and its protein product localizes to basal bodies. Therefore, we analyzed RPGRIP1L as a candidate gene for JBTS and identified loss-of-function mutations in three families with typical JBTS, including the characteristic mid-hindbrain malformation. This work identifies RPGRIP1L as a gene responsible for JBTS and establishes a central role for cilia and basal bodies in the pathophysiology of this disorder.


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CRRD Object Information
CRRD ID: 11537356
Created: 2016-09-30
Species: All species
Last Modified: 2016-09-30
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.