Document Detail


The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome.
MedLine Citation:
PMID:  17558409     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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 Martinovic; Féréchté 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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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-10
Journal Detail:
Title:  Nature genetics     Volume:  39     ISSN:  1061-4036     ISO Abbreviation:  Nat. Genet.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-06-28     Completed Date:  2007-09-04     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  875-81     Citation Subset:  IM    
Affiliation:
Institut National de la Santé et de la Recherche Médicale (INSERM) U-574, Hôpital Necker-Enfants Malades, 75015 Paris, France.
Data Bank Information
Bank Name/Acc. No.:
RefSeq/NM_015272
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MeSH Terms
Descriptor/Qualifier:
Animals
Cerebellar Diseases / genetics*
Child
Ciliary Motility Disorders / genetics*
Disease Models, Animal
Encephalocele / genetics*
Eye Diseases / genetics*
Humans
Kidney Diseases / genetics*
Mice
Mice, Inbred C3H
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Knockout
Mice, Mutant Strains
Point Mutation
Proteins / genetics*
Syndrome
Grant Support
ID/Acronym/Agency:
DK068306/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Proteins; 0/RPGRIP1 protein, human
Comments/Corrections
Comment In:
Nat Genet. 2007 Jul;39(7):818-9   [PMID:  17597771 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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