Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome by Cantagrel Vincent, Silhavy Jennifer L, Bielas Stephanie L, Swistun Dominika, Marsh Sarah E, Bertrand Julien Y, Audollent Sophie, AttiƩ-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 in American journal of human genetics (2008).

[PMID: 18674751] PubMed


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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