RPGRIP1L mutations are mainly associated with the cerebello-renal phenotype of Joubert syndrome-related disorders.

Joubert Syndrome Related Disorders (JSRDs) are autosomal recessive pleiotropic conditions sharing a peculiar cerebellar and brainstem malformation known as the “molar tooth sign” (MTS). Recently, mutations in a novel ciliary gene, RPGRIP1L, have been shown to cause both JSRDs and Meckel-Gruber syndrome. We searched for RPGRIP1L mutations in 120 patients with proven MTS and phenotypes representative of all JSRD clinical subgroups. Two homozygous mutations, the previously reported p.T615P in exon 15 and the novel c.2268_2269delA in exon 16, were detected in two out of 16 families with cerebello-renal presentation (~12%). Conversely, no pathogenic changes were found in patients with other JSRD phenotypes, suggesting that RPGRIP1L mutations are largely confined to the cerebello-renal subgroup, while they overall represent a rare cause of JSRD (<2%).