De novo and inherited monoallelic variants in TUBA4A cause ataxia and spasticity.

Alpha-tubulin 4A encoding gene (TUBA4A) has been associated with familial amyotrophic lateral sclerosis and frontotemporal dementia, based on identification of likely pathogenic variants in patients from distinct amyotrophic lateral sclerosis and frontotemporal dementia cohorts. By screening a multicentric French cohort of 448 unrelated probands presenting with cerebellar ataxia, we identified ultra-rare TUBA4A missense variants, all being absent from public databases and predicted pathogenic by multiple in silico tools. In addition, gene burden analyses in the 100 000 Genomes project (100KGP) showed enrichment of TUBA4A rare variants in the inherited ataxia group compared to controls [odds ratio: 57.0847 (10.2-576.7); P = 4.02 ×10-7]. Taken together, we report 12 patients presenting with spasticity and/or cerebellar ataxia and harbouring a predicted pathogenic TUBA4A missense mutation, including five confirmed de novo cases and a mutation previously reported in a large family presenting with spastic ataxia. Cultured fibroblasts from three patients harbouring distinct TUBA4A missense showed significant alterations in microtubule organization and dynamics, providing insight of TUBA4A variants pathogenicity. Our data confirm the identification of a hereditary spastic ataxia disease gene with variable age of onset, expanding the clinical spectrum of TUBA4A associated phenotypes.

Knowledge and attitudes toward epilepsy among teachers in Tunisia.

BACKGROUND: The importance of school teachers' knowledge of and attitudes toward epilepsy and its contribution in improving the links between the Education and Health fields, is well recognized and appreciated. In order to clarify the amount of misconceptions about epilepsy among Tunisian teachers, we conducted a web-based survey. The main objectives of our study were, first, to determine the knowledge about and attitudes toward epilepsy, and second, to specify factors associated with a better understanding of this disease. METHODS: Data were collected using a web-based survey "Google Forms". RESULTS: The study showed a positive correlation between the level of teachers' knowledge of epilepsy and their attitudes toward a person with epilepsy. Despite the knowledge gaps revealed in Tunisian teachers, the overall attitude was at large positive. Familiarity with epilepsy, whether through family or work environment, made a tremendous contribution in redressing misconceptions about epilepsy in our study. CONCLUSION: More educational interventions and programs are needed to increase teachers' familiarity with epilepsy and, consequently, increase their awareness and knowledge.