Recent Advances in Health Biotechnology During Pandemic

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in 2019, cut the epoch that will make profound fluctuates in the history of the world in social, economic, and scientific fields. Urgent needs in public health have brought with them innovative approaches, including diagnosis, prevention, and treatment. To exceed the coronavirus disease 2019 (COVID-19) pandemic, various scientific authorities in the world have procreated advances in real time polymerase chain reaction (RT-PCR) based diagnostic tests, rapid diagnostic kits, the development of vaccines for immunization, and the purposing pharmaceuticals for treatment. Diagnosis, treatment, and immunization approaches put for- ward by scientific communities are cross-fed from the accrued knowledge of multidisciplinary sciences in health biotechnology. So much so that the pandemic, urgently prioritized in the world, is not only viral infections but also has been the pulsion in the development of novel approaches in many fields such as diagnosis, treatment, translational medicine, virology, mi- crobiology, immunology, functional nano- and bio-materials, bioinformatics, molecular biol- ogy, genetics, tissue engineering, biomedical devices, and artificial intelligence technologies. In this review, the effects of the COVID-19 pandemic on the development of various scientific areas of health biotechnology are discussed

Detection of biotinidase gene mutations in Turkish patients ascertained by newborn and family screening

WOS: 000358650500011PubMed: 25754625The incidence of biotinidase deficiency in Turkey is currently one of the highest in the world. To expand upon the information about the biotinidase gene (BTD) variations in Turkish patients, we conducted a mutation screening in a large series (n = 210) of probands with biotinidase deficiency, using denaturing high-performance liquid chromatography and direct DNA sequencing. The putative effects of novel mutations were predicted by computational program. Twenty-six mutations, including six novels (p.C143F, p.T244I, c.1212-1222del11, c.1320delG, p.V457L, p.G480R) were identified. Nine of the patients were symptomatic at the initial clinical assessment with presentations of seizures, encephalopathy, and lactic acidemia. The most common mutation in this group of symptomatic patients was c.98-104 del7ins3. Among the screened patients, 72 have partial and 134 have profound biotinidase deficiency (BD) of which 106 are homozygous for BTD mutations. The common mutations (p.R157H, p.D444H, c.98-104del7ins3, p.T532M) cumulatively accounted for 72.3 % of all the mutant alleles in the Turkish population. Conclusion: The identification of common mutations and hot spot regions of the BTD gene in Turkish patients is important for mutation screening in the Turkish population and helps to ascertain carriers, may have impact on genetic counseling and implementing prevention programs.State Planning Organization of Turkey [DPT2006K1206400603]This work was funded by a grant from State Planning Organization of Turkey (Project number: DPT2006K1206400603)

STK4 (MST1) deficiency in two siblings with autoimmune cytopenias: A novel mutation

Combined immunodeficiencies (CIDs) are heterogeneous group of disorders characterized by abrogated/impaired T cell development and/or functions that resulted from diverse genetic defects. In addition to the susceptibility to infections with various microorganisms, the patients may have lymphoproliferation, autoimmunity, inflammation, allergy and malignancy. Recently, three groups have independently reported patients having mutations in STK4 gene that cause a novel autosomal recessive (AR) CID. We describe here two siblings with a novel STK4 mutation identified during the evaluation of a group of patients with features highly overlapping with those of DOCK-8 deficiency, a form of AR hyperimmunoglobulin E syndrome. The patients' clinical features include autoimmune cytopenias, viral skin (molluscum contagiosum and perioral herpetic infection) and bacterial infections, mild onychomycosis, mild atopic and seborrheic dermatitis, lymphopenia (particularly CD4 lymphopenia), and intermittent mild neutropenia. Determination of the underlying defect and reporting the patients are required for the description of the phenotypic spectrum of each immunodeficiency.Hacettepe Üniversitesi ( 010 01 101 010

Phenotypic and genotypic spectrum of Turkish patients with isovaleric acidemia

WOS: 000343331200010PubMed: 25220015We aim to investigate the genetic basis of isovaleryl-CoA dehydrogenase (IVD) gene mutations and genotype-phenotype correlations in Turkish patients. Accordingly, bi-directional sequencing was performed to screen 26 patients with isovaleric acidemia (IVA). Nine novels (c.145delC, c.234 + 3G > C, c.506_507insT, p.Glu85Gln, p.Met147Val, p.Ala268Val, p.Ile287Met, p.Gly346Asp and p.Arg382Trp) and six previously reported (c.456 + 2T > C, p.Arg21His, p.Arg21Pro, p.Arg363Cys, p.Arg363His p.Glu379Lys) pathogenic mutations were identified. Pathogenicity of the novel mutations was supported using computational programs. No clear genotype-phenotype correlation could be determined. One of the cases with the novel c.234 + 3G > C mutation has portoseptal liver fibrosis, the clinical condition that was first reported for IVA. This study is the first comprehensive report from Turkey related to IVA genetics that provides information about the high number of disease-causing novel mutations. (C) 2014 Elsevier Masson SAS. All rights reserved.[DPT-1206400603]; [TUBITAK-111S217]This study was funded by the DPT-1206400603 and TUBITAK-111S217 projects

Evaluation and identification of ıdua gene mutations in turkishpatients with mucopolysaccharidosis type I

Atçeken, Nazente (Aksaray, Yazar) Karaca, Mehmet (Aksaray, Yazar)Background/aim: This study aimed to identify IDUA gene mutations in Turkish patients morphologically (phenotypic) diagnosed with MPS type I. It also sought to discuss the possible effects of detected mutations on alpha-L-iduronidase enzyme function based on current knowledge. Materials and methods: Genetic analysis was carried out in 15 patients using direct DNA sequencing. Moreover, segregation analysis was performed among family members to predict the pathogenic effect of novel mutations, and computational programs were used to predict their functional impact. Results: Nine different mutations (c.494-1G>A, c.793-6C>G, c.793-5C>A, p.M1L, p.Y64X, p.A327P, p.W402X, p.P533L, and p.R628X) were identified. Computational analysis results supported the pathogenicity of novel mutations, suggesting improper splicing. Seven already-known polymorphisms were detected in the screened cohort as well. Conclusion: Our results revealed heterogeneity in the mutation spectrum of Turkish patients. Six of the mutations, including the novel ones, have never before been reported in the Turkish population. Moreover, 5 patients who were phenotypically diagnosed with MPS type I could not be confirmed by genetic analysis, indicating the importance of the molecular characterization of MPS subtypes

High prevalence of cerebral venous sinus thrombosis (CVST) as presentation of cystathionine beta-synthase deficiency in childhood: Molecular and clinical findings of Turkish probands

WOS: 000330013500010PubMed: 24211323Classical homocystinuria is the most commonly inherited disorder of sulfur metabolism, caused by the genetic alterations in human cystathionine beta-synthase (CBS) gene. In this study, we present comprehensive clinical findings and the genetic basis of homocystinuria in a cohort of Turkish patients. Excluding some CBS mutations, detailed genotype-phenotype correlation for different CBS mutations has not been established in literature. We aimed to make clinical subgroups according to main clinical symptoms and discussed these data together with mutational analysis results from our patients. Totally, 16 different mutations were identified; twelve of which had already been reported, and four are novel (p.N93Y, p.L251P, p.D281V and c.829-2A>T). The probands were classified into three major groups according to the clinical symptoms caused by these mutations. A psychomotor delay was the most common diagnostic symptom (n = 12, 46.2% neurological presentation), followed by thromboembolic events (n = 6, 23.1% vascular presentation) and lens ectopia, myopia or marfanoid features (n = 5, 19.2% connective tissue presentation). Pyridoxine responsiveness was 7.7%; however, with partial responsive probands, the ratio was 53.9%. In addition, five thrombophilic nucleotide changes including MTHFR c.677 C>T and c.1298 A>C, Factor V c.1691 G>A, Factor II c.20210 G>A, and SERPINE1 4G/5G were investigated to assess their contributions to the clinical spectrum. We suggest that the effect of these polymorphisms on clinical phenotype of CBS is not very clear since the distribution of thrombophilic polymorphisms does not differ among specific groups. This study provides molecular findings of 26 Turkish probands with homocystinuria and discusses the clinical presentations and putative effects of the CBS mutations. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.State Planning Organization of Turkey [DPT2006K1206400603]This work was supported by a grant from the State Planning Organization of Turkey (Project number: DPT2006K1206400603)

Homozygous Gnal Mutation Associated With Familial Childhood-Onset Generalized Dystonia

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Genotypic-phenotypic features and enzyme replacement therapy outcome in patients with mucopolysaccharidosis VI from Turkey

WOS: 000413425400010PubMed: 28884960Mucopolysaccharidosis type VI (MPS VI) is a lysosomal storage disorder (LSD) characterized by a chronic, progressive course with multiorgan involvement. In our study, clinical, biochemical, molecular findings, and response to enzyme replacement therapy (ERT) for at least 6 months were evaluated in 20 patients with MPS VI. Treatment effects on clinical findings such as liver and spleen sizes, cardiac and respiratory parameters, visual and auditory changes, joints' range of motions, endurance tests and changes in urinary glycosaminoglycan excretions, before and after ERT were analyzed. ERT caused increased physical endurance and decreased urinary dermatan sulfate/chondroitin sulfate ratios. Changes in growth parameters, cardiac, respiratory, visual, auditory findings, and joint mobility were not significant. All patients and parents reported out an increased quality of life, which were not correlated with clinical results. The most prevalent mutation was p.L321P, accounting for 58.8% of the mutant alleles and two novel mutations (p.G79E and p.E390K) were found. ERT was a safe but expensive treatment for MPS VI, with mild benefits in severely affected patients. Early treatment with ERT is mandatory before many organs and systems are involved