Mitochondria are dynamic organelles that undergo fusion and fission. These active processes occur continuously and simultaneously and are mediated by nuclear-DNA-encoded proteins that act on mitochondrial membranes. The balance between fusion and fission determines the mitochondrial morphology and adapts it to the metabolic needs of the cells. Therefore, these two processes are crucial to optimize mitochondrial function and its bioenergetics abilities. Defects in mitochondrial proteins involved in fission and fusion due to pathogenic variants in the genes encoding them result in disruption of the equilibrium between fission and fusion, leading to a group of mitochondrial diseases termed disorders of mitochondrial dynamics. In this review, the molecular mechanisms and biological functions of mitochondrial fusion and fission are first discussed. Then, mitochondrial disorders caused by defects in fission and fusion are summarized, including disorders related to MFN2, MSTO1, OPA1, YME1L1, FBXL4, DNM1L, and MFF genes.

This study describes the results of NBME (National Board of Medical Examiners) implementation in Balamand Medical School (BMS) from 2015 to 2019, after major curricular changes were introduced as of 2012. BMS students’ performance was compared with the international USMLE step 1 (United States Medical Licensing Examination, herein referred to as step 1) cohorts’ performances. The BMS students’ NBME results were analyzed over the successive academic years to assess the impact of the serial curricular changes that were implemented. This longitudinal study describes the performance of BMS preclinical second year medicine (Med II) students on all their NBME exams over 4 academic years starting 2015-2016 to 2018-2019. These scores were compared with the step 1 comparison group scores using item difficulty. The t test was computed for each of the NBME exams to check whether the scores’ differences were significant. Results revealed that all BMS cohorts scored lower than the international USMLE step 1 comparison cohorts in all disciplines across the 4 academic years except Psychiatry. However, the results were progressively approaching step 1 results, and the difference between step 1 scores and BMS students’ NBME scores became closer and not significant as of year 4. The results of the study are promising. They show that the serial curricular changes enabled BMS Med II students’ scores to reach the international cohorts’ scores after 4 academic years. Moreover, the absence of statistical difference between cohort 4 scores and step 1 cohorts is not module dependent and applies to all clinical modules. Further studies should be conducted to assess whether the results obtained for cohort 4 can be maintained.

FBXO22 encodes an F-box protein which acts as a substrate-recognition component of the SKP1-CUL1-F-box (SCF) E3 ubiquitin ligase complex. Despite its known roles in the post-translational ubiquitination and degradation of specific substrates, including histone demethylases, the impact of FBXO22 on human development remains unknown. Here, we characterize a pleiotropic syndrome with prominent prenatal onset growth restriction and notable neurodevelopmental delay across 14 cases from 12 families. Through exome and genome sequencing, we identify three distinct homozygous loss-of-function FBXO22 variants segregating with the disease: p.(Arg53Serfs*13), p.(Pro3Leufs*3) and p.(Val240Alafs*6), all predicted to lead to premature translation termination due to frameshift effects. We confirm that patient-derived primary fibroblasts are bereft of FBXO22 and show increased levels of the known substrate histone H3K9 demethylase KDM4B. Accordingly, we delineate a unique epigenetic signature for this disease in peripheral blood. Altogether, we identify and demonstrate that FBXO22 deficiency leads to a pleiotropic syndrome in humans encompassing growth restriction and neurodevelopmental delay, the pathogenesis of which may be explained by broad chromatin alterations.