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Background & Objective: Autosomal recessive cerebellar ataxias (ARCA) are rare heterogenous neurodegenerative disorders characterized by degeneration of the cerebellum and spinal cord with an early onset before the age of 20 years. PMPCA (MIM: 613036), is a key enzyme in mitochondrial protein processing which is critical for cell survival and growth. Our objective was to investigate Peptidase, Mitochondrial Processing Subunit Alpha (PMPCA) mutations linked with Spinocerebellar ataxia, autosomal recessive 2 (SCAR2). Method: In the current study, Whole Exome Sequencing (WES) was done followed by Sanger sequencing for the validation of the WES results. Results: WES results identified a novel homozygous variant, NM_015160.2: c.802C>T p.(Arg268Trp) in PMPCA gene. Mutation in this gene leads to progressive cerebellar ataxia with fine motor skills difficulties, intentional tremors, slow slurred speech and learning difficulties in a 12-year-old Saudi patient. WES results were further validated by Sanger sequencing technique. Conclusions: Identified phenotype in our case was similar as previously described for SCAR2 related conditions. To our knowledge, this is the first reported mutation in PMPCA gene leading to SCAR2 in Saudi Arabia. These findings will enrich the scarce literature, further provide a new insight on the role of PMPCA gene-related disorders leading to SCAR2 and expand the disease concept. In addition, this will help to establish a database for the disease and its causative factors will further help in controlling diseases resulting from consanguinity in Saudi population. [ABSTRACT FROM AUTHOR]

Background: The targeted inhibition of Microtubule Affinity-Regulating Kinase 4 (MARK4) using small molecule inhibitors has emerged as a promising therapeutic approach for diverse diseases, including neurological disorders such as Alzheimer's disease. Ongoing research endeavors aim to develop novel and more effective MARK4 inhibitors with enhanced target specificity and reduced off-target effects. In the present study, we sought to investigate the binding affinity and impact of Naringenin on the activity of MARK4. Methods: We employed a combination of molecular docking and other bioinformatics methods, a fluorescence-based inhibition assay, as well as a kinase activity assay to assess the binding affinity and inhibition potential of Naringenin against MARK4. Additionally, we utilized the MTT assay to examine the effect of Naringenin on the viability of two cell lines: the normal human cell line HEK-293 and the neuronal cell line SH-SY5Y. The IC50 dose of Naringenin, determined from the MTT assay, provided a valuable reference point for subsequent neuronal cell line experiments. Results: The results of the molecular docking demonstrated a robust binding affinity of Naringenin (-7.8 kcal/mol) to MARK4, affirming its potency as an inhibitor. Moreover, the fluorescence inhibition and kinase activity assays confirmed the inhibitory effect of Naringenin on MARK4. Interestingly, the MTT assay outcomes indicated that increasing concentrations of Naringenin did not significantly impact the viability of HEK 293 cells, while exhibiting a pronounced effect on SH-SY5Y neuronal cells. The IC50 concentration of Naringenin was determined to be 10.0 ± 1.33 µM for SH-SY5Y neuronal cells. Conclusion: In conclusion, this study reported Naringenin as a potential inhibitor molecule for MARK4, offering promising prospects for future therapeutic interventions in neuronal disorders specifically for Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Undergraduate selection, especially for medical degree programs, is a challenging and controversial matter for both national and international institutions. The importance of this paper lies in trying to identify the process of selecting prospective students for medical studies in Saudi Arabia. The currently applied admission criteria are the weighted average score (WAS) of the three pre-university attainments, the general secondary school (GSS), the general aptitude test (GAT), and the scientific achievement test (SAT). There is a different weightage assigned to WAS throughout the national medical institutions. It raises concern about the scientific rationale behind the differences. The present research correlates longitudinal school and university data of medical graduates using a robust methodology of multinomial logistic regression in an attempt to find statistically significant ratios of WAS. A quantitative critique of the admission process was conducted for relatively large 440 graduates of the six-year medicine program, enrolled in five academic years. Several scenarios of admission criteria have been investigated for their significant association and prediction of the academic and clinical performance of medical students. The findings suggest several choices of WAS according to the decision of educational policymakers. The future implications that may influence forthcoming decisions regarding selection criteria are humbly offered. [ABSTRACT FROM AUTHOR]

Partner and localiser of BRCA2 (PALB2), also known as FANCN, is a key tumour suppressor gene in maintaining genome integrity. Monoallelic mutations of PALB2 are associated with breast and overian cancers, while bi-allelic mutations cause Fanconi anaemia (FA). In the present study, whole exome sequencing (WES) identified a novel homozygous missense variant, NM_024675.3: c.3296C>G (p.Thr1099Arg) in PALB2 gene (OMIM: 610355) that caused FA with mild pulmonary valve stenosis and dysmorphic and atypical features, including lymphangiectasia, non-immune hydrops fetalis and right-sided pleural effusion in a preterm female baby. WES results were further validated by Sanger sequencing. WES improves the screening and detection of novel and causative genetic variants to improve management of disease. To the best of our knowledge, the present study is the first reported FA case in a Saudi family with phenotypic atypical FA features. The results support the role of PALB2 gene and pathogenic variants that may cause clinical presentation of FA. Furthermore, the present results may establish a disease database, providing a groundwork for understanding the key genomic regions to control diseases resulting from consanguinity. [ABSTRACT FROM AUTHOR]