TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23)
Joubert syndrome (JBTS) is a severe recessive neurodevelopmental ciliopathy which can affect several organ systems. Mutations in known JBTS genes account for approximately half of the cases. By homozygosity mapping and whole-exome sequencing, we identified a novel locus, JBTS23, with a homozygous sp...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , |
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eLife Sciences Publications Ltd
2015-09-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/08077 |
| _version_ | 1828107639487201280 |
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| author | Louise A Stephen Hasan Tawamie Gemma M Davis Lars Tebbe Peter Nürnberg Gudrun Nürnberg Holger Thiele Michaela Thoenes Eugen Boltshauser Steffen Uebe Oliver Rompel André Reis Arif B Ekici Lynn McTeir Amy M Fraser Emma A Hall Pleasantine Mill Nicolas Daudet Courtney Cross Uwe Wolfrum Rami Abou Jamra Megan G Davey Hanno J Bolz |
| author_facet | Louise A Stephen Hasan Tawamie Gemma M Davis Lars Tebbe Peter Nürnberg Gudrun Nürnberg Holger Thiele Michaela Thoenes Eugen Boltshauser Steffen Uebe Oliver Rompel André Reis Arif B Ekici Lynn McTeir Amy M Fraser Emma A Hall Pleasantine Mill Nicolas Daudet Courtney Cross Uwe Wolfrum Rami Abou Jamra Megan G Davey Hanno J Bolz |
| author_sort | Louise A Stephen |
| collection | DOAJ |
| description | Joubert syndrome (JBTS) is a severe recessive neurodevelopmental ciliopathy which can affect several organ systems. Mutations in known JBTS genes account for approximately half of the cases. By homozygosity mapping and whole-exome sequencing, we identified a novel locus, JBTS23, with a homozygous splice site mutation in KIAA0586 (alias TALPID3), a known lethal ciliopathy locus in model organisms. Truncating KIAA0586 mutations were identified in two additional patients with JBTS. One mutation, c.428delG (p.Arg143Lysfs*4), is unexpectedly common in the general population and may be a major contributor to JBTS. We demonstrate KIAA0586 protein localization at the basal body in human and mouse photoreceptors, as is common for JBTS proteins, and also in pericentriolar locations. We show that loss of TALPID3 (KIAA0586) function in animal models causes abnormal tissue polarity, centrosome length and orientation, and centriolar satellites. We propose that JBTS and other ciliopathies may in part result from cell polarity defects. |
| first_indexed | 2024-04-11T10:34:17Z |
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| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:34:17Z |
| publishDate | 2015-09-01 |
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| spelling | doaj.art-130e0f92665342b789f080b99454ab952022-12-22T04:29:20ZengeLife Sciences Publications LtdeLife2050-084X2015-09-01410.7554/eLife.08077TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23)Louise A Stephen0https://orcid.org/0000-0001-6795-0383Hasan Tawamie1Gemma M Davis2Lars Tebbe3Peter Nürnberg4Gudrun Nürnberg5Holger Thiele6Michaela Thoenes7Eugen Boltshauser8Steffen Uebe9Oliver Rompel10André Reis11Arif B Ekici12Lynn McTeir13Amy M Fraser14Emma A Hall15Pleasantine Mill16Nicolas Daudet17Courtney Cross18Uwe Wolfrum19Rami Abou Jamra20Megan G Davey21Hanno J Bolz22Division of Developmental Biology, The Roslin Institute, University of Edinburgh, Edinburgh, United KingdomInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDivision of Developmental Biology, The Roslin Institute, University of Edinburgh, Edinburgh, United KingdomCell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, Mainz, GermanyCologne Center for Genomics, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany; Cologne Cluster of Excellence, University of Cologne, Cologne, GermanyCologne Center for Genomics, Center for Molecular Medicine Cologne, University of Cologne, Cologne, GermanyCologne Center for Genomics, Center for Molecular Medicine Cologne, University of Cologne, Cologne, GermanyInstitute of Human Genetics, University Hospital of Cologne, Cologne, GermanyDepartment of Paediatric Neurology, University Children's Hospital Zurich, Zurich, SwitzerlandInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitute of Radiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, GermanyDivision of Developmental Biology, The Roslin Institute, University of Edinburgh, Edinburgh, United KingdomDivision of Developmental Biology, The Roslin Institute, University of Edinburgh, Edinburgh, United KingdomMedical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United KingdomMedical Research Council Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United KingdomUCL Ear Institute, University College London, London, United KingdomSchool of Osteopathic Medicine, A.T. Still University, Mesa, United StatesCell and Matrix Biology, Institute of Zoology, Johannes Gutenberg University of Mainz, Mainz, GermanyInstitute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany; Centogene, Rostock, Germany; Institute of Human Genetics, Leipzig University, Leipzig, GermanyDivision of Developmental Biology, The Roslin Institute, University of Edinburgh, Edinburgh, United KingdomInstitute of Human Genetics, University Hospital of Cologne, Cologne, Germany; Bioscientia Center for Human Genetics, Bioscientia International Business, Ingelheim am Rhein, GermanyJoubert syndrome (JBTS) is a severe recessive neurodevelopmental ciliopathy which can affect several organ systems. Mutations in known JBTS genes account for approximately half of the cases. By homozygosity mapping and whole-exome sequencing, we identified a novel locus, JBTS23, with a homozygous splice site mutation in KIAA0586 (alias TALPID3), a known lethal ciliopathy locus in model organisms. Truncating KIAA0586 mutations were identified in two additional patients with JBTS. One mutation, c.428delG (p.Arg143Lysfs*4), is unexpectedly common in the general population and may be a major contributor to JBTS. We demonstrate KIAA0586 protein localization at the basal body in human and mouse photoreceptors, as is common for JBTS proteins, and also in pericentriolar locations. We show that loss of TALPID3 (KIAA0586) function in animal models causes abnormal tissue polarity, centrosome length and orientation, and centriolar satellites. We propose that JBTS and other ciliopathies may in part result from cell polarity defects.https://elifesciences.org/articles/08077Joubert syndromeciliopathyTalpid3KIAA0586centrosomecell polarity |
| spellingShingle | Louise A Stephen Hasan Tawamie Gemma M Davis Lars Tebbe Peter Nürnberg Gudrun Nürnberg Holger Thiele Michaela Thoenes Eugen Boltshauser Steffen Uebe Oliver Rompel André Reis Arif B Ekici Lynn McTeir Amy M Fraser Emma A Hall Pleasantine Mill Nicolas Daudet Courtney Cross Uwe Wolfrum Rami Abou Jamra Megan G Davey Hanno J Bolz TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23) eLife Joubert syndrome ciliopathy Talpid3 KIAA0586 centrosome cell polarity |
| title | TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23) |
| title_full | TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23) |
| title_fullStr | TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23) |
| title_full_unstemmed | TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23) |
| title_short | TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23) |
| title_sort | talpid3 controls centrosome and cell polarity and the human ortholog kiaa0586 is mutated in joubert syndrome jbts23 |
| topic | Joubert syndrome ciliopathy Talpid3 KIAA0586 centrosome cell polarity |
| url | https://elifesciences.org/articles/08077 |
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