आणविक और आनुवंशिक चिकित्सा

Background: Mitochondrial depletion syndrome (MDS) is phenotypically heterogeneous and may affect either single or multiple organs including muscles, liver, brain, and kidneys. FBXL4-related mitochondrial depletion syndrome of encephalomyopathic type is a severe condition that begins at an early age. It is primarily linked to brain dysfunction combined with muscle weakness.

Case presentation: In the present case, a homozygous loss of function variant of FBXL4 (MIM 605654) was identified by whole exome sequencing (WES) in a three-year old Saudi girl who exhibited biochemical, and cerebral magnetic resonance imaging features consistent with mitochondrial DNA depletion syndrome 13, but had different presentations which has not been reported before.

Conclusion: MDTP13 (encephalomyopathic type) is caused by biallelic pathogenic variants in FBXL4. There is remarkable variability in genotypeto- phenotype correlation characteristic of this disease.

Background: The loss of function in TP53 gene is an early event of carcinogenesis and is now considered as a full etiological factor in oral squamous cell carcinoma (OSCC). The most common polymorphism in this gene that is associated to OSCC and has been extensively studied as a potential risk factor for the development of malignancies is the single nucleotide polymorphism (SNP) encoding either proline or arginine at residue 72. Today, despite the multiplicity of publications and approaches used, the contradiction of the results have not remove the ambiguity of the possible impact of this polymorphism in OSCC. So we aimed this meta-analysis to investigate the distribution of TP53 codon 72 genotypes and alleles in patients with OSCC and healthy matched controls, by using an ethnicity subgroups analysis.

Method: A literature search was conducted to identify studies concerning TP53 codon 72 polymorphism and OSCC risk. Retrieved publications from 2000 to 2014 were classified by ethnicity, according to the sampling collection continent. Allelic frequencies were estimated by using genotypic data and Hardy-Weinberg Equilibrium and distributions were checked with Chi-2 test. Statistical tests for contrast models of association were performed with Proline allele as reference stratum.

Results: Arg allele distribution was almost similar in both cases and controls for African and Caucasian populations whereas Arg frequency was significantly greater in cases than in controls for Asians (p=0.011). After stratified statistical analyses, we’ve found again a significant association between Arginine allele and OSCC risk in the Asian subgroup (OR=1.31; 95% CI=1.09-1.58; P=0.004).

Conclusion: This current study revealed that allelic distribution of TP53 Arg72Pro polymorphism may depend on ethnicity and latitude, and highlighted that Arginine carrier in Asian populations may be considered to be predisposed to OSCC.

SARS-CoV-2 virus suppresses host innate and adaptive immune responses, thereby allowing the virus to proliferate, and cause multiorgan failure, especially in the elderly. Respiratory viruses stimulate cyclooxygenase-2 (COX-2) to generate prostanoids including Prostaglandin D₂ (PGD₂) and thromboxane A₂. Furthermore, PGD₂ concentrations in the airways increase with aging. PGD₂ action mediated via DP₂ receptors suppresses both innate and adaptive immune responses, by inhibiting interferon-λ and stimulation of myeloid monocyte-derived suppressor cells respectively. PGD₂ and thromboxane A₂ actions via the TP receptors activate platelets leading to a prothrombotic state. Ramatroban, a small-molecule antagonist of DP₂ and TP receptors, reverses viremia-associated proinflammatory, immunosuppressive and prothrombotic processes which are similar to those induced by SARS-Cov-2. Ramatroban, used for the treatment of allergic rhinitis in Japan for the past 20 years has an excellent safety profile. Therefore, Ramatroban merits investigation as a novel immunotherapy for the treatment of COVID-19 disease.

We present a case of a 64-year-old man with a bilateral nasal obstruction. An endoscopic biopsy taken from the mass revealed a vascular clear cell tumor underneath an intact Schneiderian membrane compatible with a renal cell carcinoma. Following inquiry, it was revealed that the patient had gone through right radical nephrectomy for renal cell carcinomas 17 years prior to admission, a fact that was not known when the biopsy was taken. A following workup showed areas suspicious for metastases in lungs and maxillary sinuses. The patient started treatment with Sunitinib. On five months follow- up, the lung lesions had regressed.

Introduction: Multinodular and Vacuolating Neuronal Tumors (MVNTs) are clinically benign lesions and was recently included in the last World Health Organization Classification of Tumors of the Central Nervous System (WHO – 2016). Recent studies have discovered specific immunomarkers that classifies the MVNTs as a new neoplasm group placed within the section covering "Neuronal and mixed neuronal-glial tumors” as a WHO grade I lesion.

Case report: We present a case of a probable MVNT in a 55-year old woman, who presented with chronic pattern seizures. Conventional MRI revealed an infiltrative and multinodular pattern lesion localized in the deep left cerebral hemisphere compromising the ventral posteromedial and pulvinar surfaces of thalamus, lateral geniculate body, choroidal fissure, mammillothalamic tract, fornix and septum pellucidum, anterior commissure, extending to contralateral globus pallidus and internal capsule. Dynamic susceptibility contrast-enhanced MR perfusion and Arterial Spin Labeling (ASL) technique didn’t show any abnormalities. MR spectroscopy demonstrated a mild increase in Choline (Cho) and mild reduction in N-acetyl aspartate (NAA). No substantial difference both clinically and radiologically was observed on five years follow up.

Conclusion: The diagnosis of MVNT was made considering the extremally benign biological behavior of this tumor and the typical imaging features, despite of deep localization of the lesion, and once this kind of lesion was previously described as a “don’t touch lesion” the histological, biopsy was not performed.

Stem cells are a group of undifferentiated cells capable of regenerating somatic cells through cell division and differentiation. Among the lineage of stem cells, human mesenchymal stem cells (hMSCs) are adult stem cells that can be isolated from human tissues such as bone marrow, adipose tissues and amniotic fluids. Due to the ability of high differentiability into multiple lineages of different cell types, it is highly valuable in regenerative medicine. However, low consistent maintenance of differentiability and potency of stem cells, as well as expensive cultivation of stem cells impede the research and application of hMSCs in current medical fields. Hence, it is urging to find a more defined, low cost culture media in expansion of hMSCs without reducing its differentiability and potency. In this study, we demonstrated a well-defined xeno-free conditioned medium containing human basic fibroblast growth factor (FGF2) for hMSCs cultivation. Our results showed enhanced proliferation activity and successful maintenance of the elongated and spiral morphologies of hMSCs cultured in our conditioned medium supplemented with 100 ng/mL FGF2. More importantly, the undifferentiability of hMSCs was also validated by FACS, microscopy, qPCR and Western Blotting. We believe the present finetuned growth medium could be utilized for mass production of hMSCs.