title: Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome.
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.
authors.affiliation: Department of Neurosciences, Laboratory of Neurogenetics, Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cantagrel
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Silhavy
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Bielas
authors.forename: Dominika
authors.initials: D
authors.lastname: Swistun
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Marsh
authors.forename: Julien Y
authors.initials: JY
authors.lastname: Bertrand
authors.forename: Sophie
authors.initials: S
authors.lastname: Audollent
authors.forename: Tania
authors.initials: T
authors.lastname: Attié-Bitach
authors.forename: Kenton R
authors.initials: KR
authors.lastname: Holden
authors.forename: William B
authors.initials: WB
authors.lastname: Dobyns
authors.forename: David
authors.initials: D
authors.lastname: Traver
authors.forename: Lihadh
authors.initials: L
authors.lastname: Al-Gazali
authors.forename: Bassam R
authors.initials: BR
authors.lastname: Ali
authors.forename: Tom H
authors.initials: TH
authors.lastname: Lindner
authors.forename: Tamara
authors.initials: T
authors.lastname: Caspary
authors.forename: Edgar A
authors.initials: EA
authors.lastname: Otto
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: Ian A
authors.initials: IA
authors.lastname: Glass
authors.forename: Clare V
authors.initials: CV
authors.lastname: Logan
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Christopher
authors.initials: C
authors.lastname: Bennett
authors.forename: Francesco
authors.initials: F
authors.lastname: Brancati
authors.forename: Enza Maria
authors.initials: EM
authors.lastname: Valente
authors.forename: C Geoffrey
authors.initials: CG
authors.lastname: Woods
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Gleeson
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics*; D000015:Abnormalities, Multiple / Q000235:genetics; D000818:Animals; D001927:Brain Diseases / Q000235:genetics*; D002874:Chromosome Mapping; D002923:Cilia / Q000378:metabolism*; D019295:Computational Biology; D017124:Conserved Sequence; D020022:Genetic Predisposition to Disease; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D013577:Syndrome; D015027:Zebrafish
chemical_list: D020727:ADP-Ribosylation Factors; C530391:ARL13B protein, human