Mutations in the Cilia Gene ARL13B Lead to the Classical Form of Joubert Syndrome

• Published in: American journal of human genetics Vol. 83; no. 2; pp. 170 - 179
• Main 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, Valente, Enza Maria, Woods, C. Geoffrey, Gleeson, Joseph G.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01.08.2008; University of Chicago Press; Elsevier
• Subjects: Abnormalities, Multiple - genetics; ADP-Ribosylation Factors - genetics; Animals; Biological and medical sciences; Brain Diseases - genetics; Chromosome Mapping; Cilia - metabolism; Computational Biology; Conserved Sequence; Danio rerio; Fundamental and applied biological sciences. Psychology; General aspects. Genetic counseling; Genetic Predisposition to Disease; Genetics of eukaryotes. Biological and molecular evolution; Humans; Malformations of the nervous system; Medical genetics; Medical sciences; Molecular and cellular biology; Molecular Sequence Data; Mutation; Neurology; Neurons - metabolism; Syndrome; Zebrafish; Human; Nervous system diseases; Gene; Malformation; Joubert syndrome; Central nervous system disease; Genetics; Mutation; Genetic disease; Cerebral disorder
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1016/j.ajhg.2008.06.023

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.