YIF1B mutations cause a post-natal neurodevelopmental syndrome associated with Golgi and primary cilium alterations.

Human post-natal neurodevelopmental delay is often associated with cerebral alterations that can lead, by themselves or associated with peripheral deficits, to premature death. Here, we report the clinical features of 10 patients from six independent families with mutations in the autosomal YIF1B gene encoding a ubiquitous protein involved in anterograde traffic from the endoplasmic reticulum to the cell membrane, and in Golgi apparatus morphology. The patients displayed global developmental delay, motor delay, visual deficits with brain MRI evidence of ventricle enlargement, myelination alterations and cerebellar atrophy. A similar profile was observed in the Yif1b knockout (KO) mouse model developed to identify the cellular alterations involved in the clinical defects. In the CNS, mice lacking Yif1b displayed neuronal reduction, altered myelination of the motor cortex, cerebellar atrophy, enlargement of the ventricles, and subcellular alterations of endoplasmic reticulum and Golgi apparatus compartments. Remarkably, although YIF1B was not detected in primary cilia, biallelic YIF1B mutations caused primary cilia abnormalities in skin fibroblasts from both patients and Yif1b-KO mice, and in ciliary architectural components in the Yif1b-KO brain. Consequently, our findings identify YIF1B as an essential gene in early post-natal development in human, and provide a new genetic target that should be tested in patients developing a neurodevelopmental delay during the first year of life. Thus, our work is the first description of a functional deficit linking Golgipathies and ciliopathies, diseases so far associated exclusively to mutations in genes coding for proteins expressed within the primary cilium or related ultrastructures. We therefore propose that these pathologies should be considered as belonging to a larger class of neurodevelopmental diseases depending on proteins involved in the trafficking of proteins towards specific cell membrane compartments.

Knowledge and Attitude of Saudi Physicians Toward Cannabidiol for Pediatric Epilepsy: A Cross-Sectional Study.

Background Epilepsy is one of the most common neurological diseases. Various institutions have shown an interest to investigate the role of cannabidiol (CBD) in treating pediatric epilepsy. CBD is a chemical extracted from the cannabis plant and lacks the euphoria-inducing characteristic. Despite the FDA approval, the physicians' attitude toward CBD is controversial. Therefore, we aim to measure physicians' knowledge and acceptance of the use of CBD in managing epilepsy patients in Saudi Arabia. Objectives The aim of this study is to measure the knowledge and attitude of physicians regarding CBD use in pediatric epilepsy. Methods In this cross-sectional study, a validated electronic survey was distributed in the period between September 2021 and October 2021 among pediatricians and neurologists at King Abdulaziz Medical City. The survey consisted of four sections: demographics, the perceived knowledge regarding CBD, the knowledge test, and the attitudes toward CBD. Three-scoring systems were established to assess these sections. Results A total of 94 participants were included in this study; 50% of them were males, 81.9% of the participants were in the pediatric field, 13.8% were in the field of neurology, and 4.3% were pediatric neurologists. As for the professional tenure, approximately half of the participants were residents/trainees. Overall, respondents tend to have low perceived knowledge (94.7%) and attitude (93.6%) regarding CBD use. The perceived knowledge and attitude levels were found to be significantly associated with specialty (p < 0.001 and p = 0.001, respectively). Pediatric neurologists had a significantly higher self-assessment score, while pediatricians had the lowest attitude level (p < 0.05). For the knowledge test, surprisingly only one respondent answered all questions correctly, and age was found to be significantly associated with knowledge score (p = 0.001). Conclusion This study demonstrates that physicians have poor knowledge and attitude levels regarding the usage of CBD in pediatric epilepsy. Therefore, more education is highly suggested before the introduction of this medication to Saudi patients.