Expansion of the Genotypic and Phenotypic Spectrum of -Related Joubert Syndrome.

BACKGROUND/OBJECTIVES: Joubert syndrome (JS, MIM 213300) is a rare genetic condition 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 diagnostic tool for JS. Variants in the gene can lead to the development of several diseases, including JS type 18, Orofaciodigital syndrome IV, and Meckel-Gruber syndrome.

METHODS

We performed whole-exome sequencing (WES) in a 49-year-old woman with JS characterized by severe intellectual disability, ataxic gait, agenesis of the cerebellar vermis leading to the molar tooth sign, dystonic movements, strabismus, and nystagmus. Moreover, the patient also showed a thickened corpus callosum.

RESULTS

Molecular analysis through WES revealed the heterozygous variants c.182dup (p.G62Wfs*18) and c.1452+4del in the gene, expanding our understanding of the genetic diversity and potential phenotypic implications associated with variations.

CONCLUSIONS

To our knowledge, this is the first patient with JS and a thickened corpus callosum. Moreover, a thickened corpus callosum has never been identified in patients with pathogenic variants of the gene.