Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome.
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.
Cantagrel
Vincent
V
Department of Neurosciences, Laboratory of Neurogenetics, Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA.
Silhavy
Jennifer L
JL
Bielas
Stephanie L
SL
Swistun
Dominika
D
Marsh
Sarah E
SE
Bertrand
Julien Y
JY
Audollent
Sophie
S
Attié-Bitach
Tania
T
Holden
Kenton R
KR
Dobyns
William B
WB
Traver
David
D
Al-Gazali
Lihadh
L
Ali
Bassam R
BR
Lindner
Tom H
TH
Caspary
Tamara
T
Otto
Edgar A
EA
Hildebrandt
Friedhelm
F
Glass
Ian A
IA
Logan
Clare V
CV
Johnson
Colin A
CA
Bennett
Christopher
C
Brancati
Francesco
F
Valente
Enza Maria
EM
Woods
C Geoffrey
CG
Gleeson
Joseph G
JG
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
D020727:ADP-Ribosylation Factors; C530391:ARL13B protein, human