Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination

Background and purpose Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy. Methods Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided. Results Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur. Conclusions NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels

Epstein-Barr virus: clinical and epidemiological revisits and genetic basis of oncogenesis

Epstein-Barr virus (EBV) is classified as a member in the order herpesvirales, family herpesviridae, subfamily gammaherpesvirinae and the genus lymphocytovirus. The virus is an exclusively human pathogen and thus also termed as human herpesvirus 4 (HHV4). It was the first oncogenic virus recognized and has been incriminated in the causation of tumors of both lymphatic and epithelial nature. It was reported in some previous studies that 95% of the population worldwide are serologically positive to the virus. Clinically, EBV primary infection is almost silent, persisting as a life-long asymptomatic latent infection in B cells although it may be responsible for a transient clinical syndrome called infectious mononucleosis. Following reactivation of the virus from latency due to immunocompromised status, EBV was found to be associated with several tumors. EBV linked to oncogenesis as detected in lymphoid tumors such as Burkitt's lymphoma (BL), Hodgkin's disease (HD), post-transplant lymphoproliferative disorders (PTLD) and T-cell lymphomas (e.g. Peripheral T-cell lymphomas; PTCL and Anaplastic large cell lymphomas; ALCL). It is also linked to epithelial tumors such as nasopharyngeal carcinoma (NPC), gastric carcinomas and oral hairy leukoplakia (OHL). In vitro, EBV many studies have demonstrated its ability to transform B cells into lymphoblastoid cell lines (LCLs). Despite these malignancies showing different clinical and epidemiological patterns when studied, genetic studies have suggested that these EBV- associated transformations were characterized generally by low level of virus gene expression with only the latent virus proteins (LVPs) upregulated in both tumors and LCLs. In this review, we summarize some clinical and epidemiological features of EBV- associated tumors. We also discuss how EBV latent genes may lead to oncogenesis in the different clinical malignancie

Prevalence and Associated Factors of Vitamin D Deficiency in High Altitude Region in Saudi Arabia: Three-Year Retrospective Study

Mostafa Abdelsalam,1,2 Eman Nagy,2 Mohamed Abdalbary,2 Mona Abdellatif Alsayed,1,3 Amr Abouzed Salama Ali,4 Reham Metwally Ahmed,1 Abdulbadie Saleh M Alsuliamany,1 Ali H Alyami,5– 7 Raad MM Althaqafi,8 Raghad M Alsaqqa,9 Safaa Ibrahim Ali,10 Bakar Aljohani,11 Ahmed Abdullah Alghamdi,12 Faisal A Alghamdi,9 Adnan A Alsulaimani1 1Internal Medicine Department, Alameen General Hospital, Taif, Saudi Arabia; 2Mansoura Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 3Department of Pediatrics, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 4Mansoura Medical District, Family Medicine Hospitals, Ministry of Health, Mansoura, Egypt; 5Department of Surgery, Ministry of the National Guard – Health Affairs, Jeddah, Saudi Arabia; 6Department of Surgery, Abdullah International Medical Research Center, Jeddah, Saudi Arabia; 7Department of Orthopedics, King Saud Bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 8Orthopedic Surgery Department, King Abdulaziz Specialist Hospital, Taif, Saudi Arabia; 9College of Medicine, Taif University, Taif, Saudi Arabia; 10General Medicine Faculty, Sechenov University, Moscow City, Russian Federation; 11Neuroradiology, AlHada Military Hospital, Taif, Saudi Arabia; 12College of Medicine, Al-Baha University, Al Baha, Saudi ArabiaCorrespondence: Eman Nagy, Mansoura Nephrology and Dialysis Unit, Internal Medicine Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt, Email [email protected]: Vitamin D has many functions in the human body, and its deficiency is associated with skeletal and non-skeletal diseases. Vitamin D deficiency (blood level of 25 (OH) vitamin D < 20 ng/mL) has been reported worldwide, including Kingdom of Saudi Arabia (KSA). Its prevalence and associated factors vary according to KSA. Therefore, this study aimed to explore the prevalence and risk factors of vitamin D deficiency in the Taif region of KSA.Methods: This retrospective study included patients who attended outpatient clinics at the Alameen General Hospital from 2019 to 2021. Demographic, clinical, and laboratory data were collected using a hospital software system.Results: The study included 2153 patients and vitamin D deficiency was diagnosed in 900 (41.8%) of whom were diagnosed with vitamin D deficiency. It was more common in males (P=0.021), younger age (< 0.001), and in patients without comorbidities. There was a positive correlation between 25 (OH) vitamin D levels and blood cholesterol, high-density lipoprotein, calcium, and vitamin B12 levels. In the binary logistic regression analysis, age was the most significant predictor (P< 0.001), followed by the absence of thyroid disease (P=0.012) and asthma (P=0.030).Conclusion: Vitamin D deficiency is common in the Saudi population despite sunny weather in KSA. It is more prevalent among males, younger individuals, and those without comorbidities such as thyroid diseases and asthma.Keywords: vitamin D, prevalence, risk factors, KSA, calciu