guanosine-triphosphate and Kidney-Diseases--Cystic

ARL13B encodes for the ADP-ribosylation factor-like 13B GTPase, which is required for normal cilia structure and Sonic hedgehog (Shh) signaling. Disruptions in cilia structure or function lead to a class of human disorders called ciliopathies. Joubert syndrome is characterized by a wide spectrum of symptoms, including a variable degree of intellectual disability, ataxia, and ocular abnormalities. Here we report a novel homozygous missense variant c.[223G>A] (p.(Gly75Arg) in the ARL13B gene, which was identified by whole-exome sequencing of a trio from a consanguineous family with multiple-affected individuals suffering from intellectual disability, ataxia, ocular defects, and epilepsy. The same variant was also identified in a second family. We saw a striking difference in the severity of ataxia between affected male and female individuals in both families. Both ARL13B and ARL13B-c.[223G>A] (p.(Gly75Arg) expression rescued the cilia length and Shh defects displayed by Arl13b

Topics: Abnormalities, Multiple; Adolescent; ADP-Ribosylation Factors; Adult; Animals; Cell Line, Tumor; Cells, Cultured; Cerebellum; Child; Eye Abnormalities; Female; Guanosine Triphosphate; Homozygote; Humans; Kidney Diseases, Cystic; Loss of Function Mutation; Male; Mice; Mutation, Missense; Pedigree; Retina