New insights into -related Joubert syndrome.

Purpose: In this study, we describe the phenotype and genotype of the largest cohort of patients with Joubert syndrome (JS) carrying pathogenic variants on one of the most frequent causative genes, .

Methods: We selected 53 patients with pathogenic variants on , compiled and analysed their clinical, neuroimaging and genetic information and compared it to previous literature.

Results: Developmental delay (motor and language) was nearly constant but patients had normal intellectual efficiency in 74% of cases (20/27 patients) and 68% followed mainstream schooling despite learning difficulties.

Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy.

Heterozygous de novo variants in the eukaryotic elongation factor EEF1A2 have previously been described in association with intellectual disability and epilepsy but never functionally validated. Here we report 14 new individuals with heterozygous EEF1A2 variants. We functionally validate multiple variants as protein-damaging using heterologous expression and complementation analysis.

Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias.

Next-generation sequencing (NGS) has an established diagnostic value for inherited ataxia. However, the need of a rigorous process of analysis and validation remains challenging. Moreover, copy number variations (CNV) or dynamic expansions of repeated sequence are classically considered not adequately detected by exome sequencing technique.

PNPLA2 mutation: a paediatric case with early onset but indolent course.

Neutral lipid storage disease (NLSD) due to PNPLA2 mutation is a rare disorder with a severe muscular and cardiac outcome. All but one reported cases have been diagnosed during adulthood. It is thus ordinarily distinguished from Chanarin-Dorfman syndrome, a paediatric NLSD with a more widespread symptomatology.