title: The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome.
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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U-574, Hôpital Necker-Enfants Malades, 75015 Paris, France.
authors.forename: Marion
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authors.forename: Jéléna
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authors.forename: Jean Pierre
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authors.lastname: Berthélémé
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authors.forename: Fiona
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authors.lastname: Vekemans
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authors.lastname: Rüther
authors.forename: Sylvie
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authors.lastname: Schneider-Maunoury
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authors.lastname: Attié-Bitach
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authors.lastname: Saunier
mesh_terms: D000818:Animals; D002526:Cerebellar Diseases / Q000235:genetics*; D002648:Child; D002925:Ciliary Motility Disorders / Q000235:genetics*; D003598:Cytoskeletal Proteins; D004195:Disease Models, Animal; D004677:Encephalocele / Q000235:genetics*; D005128:Eye Diseases / Q000235:genetics*; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D017354:Point Mutation; D011506:Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D003598:Cytoskeletal Proteins; D011506:Proteins; C415903:RPGRIP1 protein, human