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Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome |
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| Authors: | Cantagrel Vincent Silhavy Jennifer L Bielas Stephanie L Swistun Dominika Marsh Sarah E Bertrand Julien Y Audollent Sophie Attié-Bitach Tania Holden Kenton R Dobyns William B Traver David Al-Gazali Lihadh Ali Bassam R Lindner Tom H Caspary Tamara Otto Edgar A Hildebrandt Friedhelm Glass Ian A Logan Clare V Johnson Colin A Bennett Christopher Brancati Francesco;International Joubert Syndrome Related Disorders Study Group Valente Enza Maria Woods C Geoffrey Gleeson Joseph G |
| Institution: | 1 Laboratory of Neurogenetics, Howard Hughes Medical Institute, Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA 2 Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0380, USA 3 Département de Génétique et INSERM U781, Hôpital Necker-Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France 4 Neurosciences Section, Greenwood Genetic Center, 101 Gregor Mendel Circle, Greenwood, SC 29646, USA 5 Departments of Neuroscience and Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA 6 Department of Human Genetics, The University of Chicago, Room 319 CLSC, 920 E. 58th Street, IL 60637, USA 7 Department of Pediatrics, United Arab Emirates University, Faculty of Medicine and Health Sciences, PO Box 17666, Al-Ain, United Arab Emirates 8 Department of Pathology, United Arab Emirates University, Faculty of Medicine and Health Sciences, PO Box 17666, Al-Ain, United Arab Emirates 9 Division of Nephrology, Department of Internal Medicine III, University Clinic Leipzig, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany 10 Department of Human Genetics, Emory University School of Medicine, 615 Michael St. Suite 301, Atlanta, GA 30322-1047, USA 11 Department of Pediatrics, University of Michigan, 8220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-5640, USA 12 Department of Pediatrics and Medicine, University of Washington School of Medicine, Childrens Hospital Regional Medical Center, A-7937, 4800 Sand Point Way NE, Seattle, WA 98105, USA 13 Section of Ophthalmology and Neurosciences, Wellcome Trust Brenner Building, Leeds Institute of Molecular Medicine, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK 14 Yorkshire Regional Genetics Service, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK 15 Instituto di Ricovero e Cura a Carattere Scientifico, Casa Sollievo della Sofferenza, Mendel Institute, viale Regina Margherita 261, 00198 Rome, Italy 16 Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke's Hospital, Cambridge CB2 0XY, UK |
| Abstract: | Joubert syndrome (JS) and related disorders are a group of autosomal-recessive conditions sharing the "molar tooth sign" on axial brain MRI, together with cerebellar vermis hypoplasia, ataxia, and psychomotor delay. JS is suggested to be a disorder of cilia function and is part of a spectrum of disorders involving retinal, renal, digital, oral, hepatic, and cerebral organs. We identified mutations in ARL13B in two families with the classical form of JS. ARL13B belongs to the Ras GTPase family, and in other species is required for ciliogenesis, body axis formation, and renal function. The encoded Arl13b protein was expressed in developing murine cerebellum and localized to the cilia in primary neurons. Overexpression of human wild-type but not patient mutant ARL13B rescued the Arl13b scorpion zebrafish mutant. Thus, ARL13B has an evolutionarily conserved role mediating cilia function in multiple organs. |
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