The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome

Marion Delous, Lekbir Baala, Rémi Salomon, Christine Laclef, Jeanette Vierkotten, Kàlmàn Tory, Christelle Golzio, Tiphanie Lacoste, Laurianne Besse, Catherine Ozilou, Imane Moutkine, Nathan E. Hellman, Isabelle Anselme, Flora Silbermann, Christine Vesque, Christoph Gerhardt, Eleanor Rattenberry, Matthias T.F. Wolf, Marie Claire Gubler, Jéléna MartinovicFéréchté Encha-Razavi, Nathalie Boddaert, Marie Gonzales, Marie Alice Macher, Hubert Nivet, Gérard Champion, Jean Pierre Berthélémé, Patrick Niaudet, Fiona McDonald, Friedhelm Hildebrandt, Colin A. Johnson, Michel Vekemans, Corinne Antignac, Ulrich Rüther, Sylvie Schneider-Maunoury, Tania Attié-Bitach, Sophie Saunier

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310 Citations (Scopus)

Abstract

Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder.

Original languageEnglish
Pages (from-to)875-881
Number of pages7
JournalNature genetics
Volume39
Issue number7
DOIs
Publication statusPublished - Jul 1 2007

ASJC Scopus subject areas

  • Genetics

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    Delous, M., Baala, L., Salomon, R., Laclef, C., Vierkotten, J., Tory, K., Golzio, C., Lacoste, T., Besse, L., Ozilou, C., Moutkine, I., Hellman, N. E., Anselme, I., Silbermann, F., Vesque, C., Gerhardt, C., Rattenberry, E., Wolf, M. T. F., Gubler, M. C., ... Saunier, S. (2007). The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nature genetics, 39(7), 875-881. https://doi.org/10.1038/ng2039