Cantagrel et al. (2008) studied 2 families with Joubert syndrome in which novel mutations in the ARL13B gene were subsequently found. The phenotype consisted predominantly of classical Joubert syndrome, with all patients displaying the molar tooth sign. In ... Cantagrel et al. (2008) studied 2 families with Joubert syndrome in which novel mutations in the ARL13B gene were subsequently found. The phenotype consisted predominantly of classical Joubert syndrome, with all patients displaying the molar tooth sign. In the Pakistani pedigree in which the disorder was mapped, 2 of the 3 affected individuals had a small occipital encephalocele. In the other family, from the United States, there was no occipital encephalocele, and there were no other supratentorial cerebral abnormalities. Diagnostic ultrasound, performed on both families, found no renal abnormalities. The possibility that renal symptoms could develop in the affected individuals was considered, as studies of urinary concentration defects, a more sensitive measure of early kidney involvement, were not available from any of the patients.
The JBTS8 interval defined by Cantagrel et al. (2008) contained 41 genes, of which 4 were considered strong candidates based on their identification within the cilia proteome. In the Pakistani family in which linkage to 3p12.3-q12.3 was established, ... The JBTS8 interval defined by Cantagrel et al. (2008) contained 41 genes, of which 4 were considered strong candidates based on their identification within the cilia proteome. In the Pakistani family in which linkage to 3p12.3-q12.3 was established, Cantagrel et al. (2008) identified a homozygous missense mutation in exon 3 of the ARL13B gene (R79Q; 608922.0001). The affected individual from another family was compound heterozygous for a nonsense mutation (W82X; 608922.0002) and a missense mutation (R200C; 608922.0003). Overexpression of human wildtype, but not patient mutant, ARL13B rescued the Arl13b 'scorpion' zebrafish mutant, demonstrating that ARL13B has an evolutionarily conserved role in mediating cilia function in multiple organs.