Expansion of the Genotypic and Phenotypic Spectrum of <em>TCTN3</em> Related Joubert Syndrome

Background/Objectives: Joubert syndrome (JS, MIM 213300) is a rare genetic condi-tion characterized by respiratory control disturbances, abnormal eye movements, ataxia, cognitive impairment, and the notable agenesis of the cerebellar vermis. The molar tooth sign visible in magnetic resonance imaging of the brain serves as a diag-nostic tool for JS. Variants in TCTN3 gene can lead to the development of several dis-eases, including JS type 18, Orofaciodigital syndrome IV and Meckel-Gruber syndrome. Methods: We performed whole-exome sequencing (WES) in a49-year-old woman with JS characterized by severe intellectual disability, ataxic gait, agenesis of the cerebellar vermis leading to molar tooth sign, dystonic movements, strabismus, and nystagmus. Moreover, the patient also showed thickened corpus callosum. Results: Molecular analysis through whole-exome sequencing (WES)revealed the heterozygous variants c.182dup (p.G62Wfs*18) and c.1452+4del in TCTN3 gene, expanding our understand-ing of the genetic diversity and potential phenotypic implications associated with TCTN3 variations. Conclusions: To our knowledge, this is the first patient with JS and thickened corpus callosum. Moreover, thickened corpus callosum has never been iden-tified in patients with pathogenic variants of the TCTN3 gene.