Clinical and molecular analysis in Joubert syndrome.

Joubert syndrome is an autosomal recessive disorder comprising cerebellar hypoplasia, hypotonia, developmental delay, abnormal respiratory patterns, and abnormal eye movements. The biochemical basis of the Joubert syndrome is unknown. We ascertained a cohort of 50 patients with the Joubert syndrome to evaluate the presence of associated malformations, and to initiate studies leading to the identification of the Joubert syndrome gene. Only 8% of patients had polydactyly, 4% colobomas, 2% renal cysts, and 2% had soft tissue tumors of the tongue. In addition, we evaluated the WNT1 gene as a candidate gene for the Joubert syndrome based on its expression in the developing cerebellum and an associated mutation in the swaying mouse. We searched for mutations in WNT1 in a series of Joubert syndrome patients and no mutations were detected. Our analysis suggests that mutations in WNT1 do not cause the Joubert syndrome.