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

Publication type:
Journal article
Metadata:
Autoren
  • Heleen H Arts
  • Dan Doherty
  • Sylvia EC van Beersum
  • Melissa A Parisi
  • Stef JF Letteboer
  • Nicholas T Gorden
  • Theo A Peters
  • Tina Maerker
  • Krysta Voesenek
  • Aileen Kartono
  • Hamit Ozyurek
  • Federico M Farin
  • Hester Y Kroes
  • Uwe Wolfrum
  • Han G Brunner
  • Frans PM Cremers
  • Ian A Glass
  • Nine VAM Knoers
  • Ronald Roepman
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000247619800019&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1038/ng2069
Externe Identifier
  • Clarivate Analytics Document Solution ID: 184CX
  • PubMed Identifier: 17558407
ISSN
1061-4036
Ausgabe der Veröffentlichung
7
Zeitschrift
NATURE GENETICS
Paginierung
882 - 888
Datum der Veröffentlichung
2007
Status
Published
Titel
Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome
Sub types
  • Article
Ausgabe der Zeitschrift
39

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
  • Heleen H Arts
  • Dan Doherty
  • Sylvia EC van Beersum
  • Melissa A Parisi
  • Stef JF Letteboer
  • Nicholas T Gorden
  • Theo A Peters
  • Tina Märker
  • Krysta Voesenek
  • Aileen Kartono
  • Hamit Ozyurek
  • Federico M Farin
  • Hester Y Kroes
  • Uwe Wolfrum
  • Han G Brunner
  • Frans PM Cremers
  • Ian A Glass
  • Nine VAM Knoers
  • Ronald Roepman
DOI
10.1038/ng2069
eISSN
1546-1718
ISSN
1061-4036
Ausgabe der Veröffentlichung
7
Zeitschrift
Nature Genetics
Sprache
en
Online publication date
2007
Paginierung
882 - 888
Datum der Veröffentlichung
2007
Status
Published
Herausgeber
Springer Science and Business Media LLC
Herausgeber URL
http://dx.doi.org/10.1038/ng2069
Datum der Datenerfassung
2023
Titel
Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome
Ausgabe der Zeitschrift
39

Data source: Crossref

Abstract
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-Løken 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.
Addresses
  • Department of Human Genetics, Radboud University Nijmegen Medical Centre and Nijmegen Centre for Molecular Life Sciences, 6500 HB Nijmegen, The Netherlands.
Autoren
  • Heleen H Arts
  • Dan Doherty
  • Sylvia EC van Beersum
  • Melissa A Parisi
  • Stef JF Letteboer
  • Nicholas T Gorden
  • Theo A Peters
  • Tina Märker
  • Krysta Voesenek
  • Aileen Kartono
  • Hamit Ozyurek
  • Federico M Farin
  • Hester Y Kroes
  • Uwe Wolfrum
  • Han G Brunner
  • Frans PM Cremers
  • Ian A Glass
  • Nine VAM Knoers
  • Ronald Roepman
DOI
10.1038/ng2069
eISSN
1546-1718
Externe Identifier
  • PubMed Identifier: 17558407
Funding acknowledgements
  • NCRR NIH HHS: K12-RR023265
  • NIEHS NIH HHS: P30ES07033
  • NICHD NIH HHS: P30 HD02274
  • NINDS NIH HHS: K23-NS45832
  • NICHD NIH HHS: K24-HD46712
Open access
false
ISSN
1061-4036
Ausgabe der Veröffentlichung
7
Zeitschrift
Nature genetics
Schlüsselwörter
  • Cell Line
  • Cilia
  • Animals
  • Humans
  • Rats
  • Ciliary Motility Disorders
  • Cerebellar Diseases
  • Eye Diseases
  • Kidney Diseases
  • Syndrome
  • Adaptor Proteins, Signal Transducing
  • Proteins
  • Cytoskeletal Proteins
  • Pedigree
  • Molecular Sequence Data
  • Adult
  • Female
  • Male
Sprache
eng
Medium
Print-Electronic
Online publication date
2007
Paginierung
882 - 888
Datum der Veröffentlichung
2007
Status
Published
Datum der Datenerfassung
2007
Titel
Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.
Sub types
  • Research Support, Non-U.S. Gov't
  • Journal Article
  • Research Support, N.I.H., Extramural
Ausgabe der Zeitschrift
39

Data source: Europe PubMed Central

Abstract
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-Løken 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.
Date of acceptance
2007
Autoren
  • Heleen H Arts
  • Dan Doherty
  • Sylvia EC van Beersum
  • Melissa A Parisi
  • Stef JF Letteboer
  • Nicholas T Gorden
  • Theo A Peters
  • Tina Märker
  • Krysta Voesenek
  • Aileen Kartono
  • Hamit Ozyurek
  • Federico M Farin
  • Hester Y Kroes
  • Uwe Wolfrum
  • Han G Brunner
  • Frans PM Cremers
  • Ian A Glass
  • Nine VAM Knoers
  • Ronald Roepman
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/17558407
DOI
10.1038/ng2069
Funding acknowledgements
  • NCRR NIH HHS: K12-RR023265
  • NINDS NIH HHS: K23-NS45832
  • NICHD NIH HHS: K24-HD46712
  • NICHD NIH HHS: P30 HD02274
  • NIEHS NIH HHS: P30ES07033
ISSN
1061-4036
Ausgabe der Veröffentlichung
7
Zeitschrift
Nat Genet
Schlüsselwörter
  • Adaptor Proteins, Signal Transducing
  • Adult
  • Animals
  • Cell Line
  • Cerebellar Diseases
  • Cilia
  • Ciliary Motility Disorders
  • Cytoskeletal Proteins
  • Eye Diseases
  • Female
  • Humans
  • Kidney Diseases
  • Male
  • Molecular Sequence Data
  • Pedigree
  • Proteins
  • Rats
  • Syndrome
Sprache
eng
Country
United States
Paginierung
882 - 888
PII
ng2069
Datum der Veröffentlichung
2007
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2007
Titel
Mutations in the gene encoding the basal body protein RPGRIP1L, a nephrocystin-4 interactor, cause Joubert syndrome.
Sub types
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
Ausgabe der Zeitschrift
39

Data source: PubMed

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