2. Academic Validation
  3. Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome

Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome

  • Am J Hum Genet. 2008 Aug;83(2):170-9. doi: 10.1016/j.ajhg.2008.06.023.
Vincent Cantagrel 1,  Jennifer L Silhavy,  Stephanie L Bielas,  Dominika Swistun,  Sarah E Marsh,  Julien Y Bertrand,  Sophie Audollent,  Tania Attié-Bitach,  Kenton R Holden,  William B Dobyns,  David Traver,  Lihadh Al-Gazali,  Bassam R Ali,  Tom H Lindner,  Tamara Caspary,  Edgar A Otto,  Friedhelm Hildebrandt,  Ian A Glass,  Clare V Logan,  Colin A Johnson,  Christopher Bennett,  Francesco Brancati,  International Joubert Syndrome Related Disorders Study Group,  Enza Maria Valente,  C Geoffrey Woods,  Joseph G Gleeson
Affiliations

Affiliation

  • 1 Department of Neurosciences, Laboratory of Neurogenetics, Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA.
PMID: 18674751 DOI: 10.1016/j.ajhg.2008.06.023
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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