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Temel Tıp Bilimleri Bölümü Makale Koleksiyonu

Permanent URI for this collectionhttps://hdl.handle.net/20.500.12294/2849

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Citation - Scopus: 10
RB1 Gene Mutations and Genetic Spectrum in Retinoblastoma Cases
(Lippincott Williams and Wilkins, 2024) Odemis, Demet Akdeniz; Kebudi, Rejin; Bayramova, Jamila; Erciyas, Seda Kilic; Turkcan, Gozde Kuru; Tuncer, Seref Bugra; Erdogan, Ozge Sukruoglu; Celik, Betul; Gultaslar, Busra Kurt; Bay, Sema Buyukkapu; Tuncer, Samuray; Yazici, Hulya
The aim of the study was to investigate the frequency and types of mutations on the retinoblastoma gene (RB1 gene) in Turkish population. RB1 gene mutation analysis was performed in a total of 219 individuals (122 probands with retinoblastoma, 14 family members with retinoblastoma and 83 clinically healthy family members). All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and the large deletions and duplications were investigated using the MLPA analysis and CNV algorithm. The bilateral/trilateral retinoblastoma rate was 66% in the study population. The general frequency of RB1 gene mutation in the germline of the patients with retinoblastoma was 41.9%. Approximately 51.5% of the patients were diagnosed earlier than 12 months old, and de novo mutation was found in 32.4% of the patients. Germline small genetic rearrangement mutations were detected in 78.9% of patients and LGRs were detected in 21.1% of patients. An association was detected between the eye color of the RB patients and RB1 mutations. 8 of the mutations detected in the RB1 gene were novel in the study.
Citation - WoS: 1
Citation - Scopus: 1
High Expression of miR-218-5p in the Peripheral Blood Stream and Tumor Tissues of Pediatric Patients with Sarcomas
(Springer, 2024) Ozdenoglu, Fazilet Yildiz; Odemis, Demet Akdeniz; Erciyas, Seda Kilic; Tuncer, Seref Bugra; Gultaslar, Busra Kurt; Salduz, Ahmet; Buyukkapu, Sema; Olgac, Necat Vakur; Kebudi, Rejin; Yazici, Hulya
Sarcomas are malignant tumors that may metastasize and the course of the disease is highly aggressive in children and young adults. Because of the rare incidence of sarcomas and the heterogeneity of tumors, there is a need for non-invasive diagnostic and prognostic biomarkers in sarcomas. The aim of the study was to investigate the level of miR-218-5p in peripheral blood and tumor tissue samples of Ewing's sarcoma, osteosarcoma, spindle cell sarcoma patients, and healthy controls, and assessed whether the corresponding molecule was a diagnostic and prognostic biomarker. The study was performed patients (n = 22) diagnosed and treated with Ewing's sarcoma and osteosarcoma and in a control group of 22 healthy children who were matched for age, gender, and ethnicity with the patient group. The expression level of miR-218-5p in RNA samples from peripheral blood and tissue samples were analyzed using the RT-PCR and the expression level of miR-218-5p was evaluated by comparison with the levels in patients and healthy controls. The expression level of miR-218-5p was found to be statistically higher (3.33-fold, p = 0.006) in pediatric patients with sarcomas and when the target genes of miR-218-5p were investigated using the bioinformatics tools, the miR-218-5p was found as an important miRNA in cancer. In this study, the miR-218-5p was shown for the first time to have been highly expressed in the peripheral blood and tumor tissue of sarcoma patients. The results suggest that miR-218-5p can be used as a diagnostic and prognostic biomarker in sarcomas and will be evaluated as an important therapeutic target.
Citation - Scopus: 3
Genetic Alterations in Lung Cancer
(Kare Publ, 2024) Bayramova, Jamila; Tarakci, Elif; Huseynova, Gumru; Yazici, Hilal; Yazici, Hulya
Lung cancer is the leading cause of cancer -related deaths worldwide. Due to the prevalence of late -stage diagnoses, treatment options are frequently constrained. Molecular profiling of lung cancer is crucial for the clinical management and successful therapy of the disease because lung cancer originates from a multilayered carcinogenesis consisting of multiple genetic and epigenetic abnormalities. The potential of anomalies involved in carcinogenesis as biomarkers that can be used in the diagnosis and treatment of lung cancer has begun to be evaluated due to the development of new generation sequencing methods and their more frequent application in the clinic. This review presents information regarding the genetic alterations responsible for the malignant transformation of lung cells. The article highlights the predominant gene mutations that are specific to a particular subtype of lung cancer, their impact on the clinical progression of the disease, and the response to treatment. However, in summarizing all genetic features, the latest information from the NCCN v2.2024 guide was taken into account.
Citation - WoS: 2
Citation - Scopus: 2
Factors Associated with Psychological Distress During Genetic Counseling in High-Risk Women with Breast Cancer in Turkey
(Springer Science and Business Media Deutschland GmbH, 2024) Anuk, Dilek; Tuncer, Seref Bugra; Ozkan, Mine; Yazici, Hulya
Purpose This study aims to shed light on the rather neglected area of research of psychological distress in women facing genetic counselling in Turkey, where few institutions providing such counselling exist. Methods 105 breast cancer patients presenting for genetic testing completed a sociodemographic and clinical questionnaire as well as validated structured questionnaires including the Beck Depression Inventory (BDI), the State-Trait Anxiety Inventory (STAI-S/T) and the Health Motivation Sub-dimension of Champion's Health Belief Model Scale. Results 69.5% of the participants had lost a family member from cancer; 80% said the term "cancer" elicited negative thoughts (e.g., death, fear, and incurable disease). 62.9% and 37.1% attributed cancer to stress or sorrow, and genetic susceptibility, respectively. There was a negative association between health motivation and BDI scores (r:-0.433, p < 0.001). Married individuals had higher BDI and STAI-S scores (p = 0.001, p = 0.01 respectively), as well as lower STAI-T scores (p = 0.006). BDI, STAI-S and STAI-T scores were higher in those refusing genetic testing (p < 0.001, p < 0.001, p = 0.003 respectively) and those with metastases (p = 0.03, p = 0.01, p = 0.03 respectively). Furthermore, individuals with low health motivation were more likely to exhibit high BDI scores (p < 0.001) and low STAI-T scores (p = 0.02). Conclusion Common perceptions and beliefs about cancer and genetic testing during genetic counselling were found to have a negative impact on distress in high-risk women with breast cancer. The negative relationship between psychological distress and health motivation may reduce patients' compliance with genetic counselling recommendations. A comprehensive psychological evaluation should be considered as an important part of genetic counselling.
Citation - WoS: 3
Citation - Scopus: 3
Genetic Alterations in Lung Cancer
(Kare Publ, 2024) Bayramova, Jamila; Tarakci, Elif; Huseynova, Gumru; Yazici, Hilal; Yazici, Hulya
Lung cancer is the leading cause of cancer-related deaths worldwide. Due to the prevalence of late-stage diagnoses, treatment options are frequently constrained. Molecular profiling of lung cancer is crucial for the clinical management and successful therapy of the disease because lung cancer originates from a multilayered carcinogenesis consisting of multiple genetic and epigenetic abnormalities. The potential of anomalies involved in carcinogenesis as biomarkers that can be used in the diagnosis and treatment of lung cancer has begun to be evaluated due to the development of new generation sequencing methods and their more frequent application in the clinic. This review presents information regarding the genetic alterations responsible for the malignant transformation of lung cells. The article highlights the predominant gene mutations that are specific to a particular subtype of lung cancer, their impact on the clinical progression of the disease, and the response to treatment. However, in summarizing all genetic features, the latest information from the NCCN v2.2024 guide was taken into account.
Citation - WoS: 2
Citation - Scopus: 2
Subcortical Volume Changes in Schizophrenia and Bipolar Disorder: A Quantitative MRI Study
(Universidad de la Frontera, 2024) Demir, Mehmet; Findikli, Ebru; Tuncel, Deniz; Atay, Emre; Baykara, Murat; Acer, Niyazi; Doganer, Adem
Volume abnormalities in subcortical structures, including the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus have been observed in schizophrenia (SZ) and bipolar disorder (BD), not all individuals with these disorders exhibit such changes. In addition, the specific patterns and severity of volume changes may vary between individuals and at different stages of the disease. The study aims to compare the volumes of these subcortical structures between healthy subjects and individuals diagnosed with SZ or BD. Volumetric measurements of lateral ventricle, globus palllidus, caudate, putamen, hippocampus, and amygdale were made by MRI in 52 healthy subjects (HS), 33 patients with SZ, and 46 patients with BD. Automatic segmentation methods were used to analyze the MR images with VolBrain and MRICloud. Hippocampus, amygdala and lateral ventricle increased in schizophrenia and bipolar disorder patients in comparison with control subjects using MRIcloud. Globus pallidus and caudate volume increased in patients with schizophrenia and bipolar disorder compared control subjects using Volbrain. We suggested that our results will contribute in schizophrenia and bipolar disorder patients that assessment of the sub-cortical progression, pathology, and anomalies of subcortical brain compositions. In patients with psychiatric disorders, VolBrain and MRICloud can detect subtle structural differences in the brain.
Citation - WoS: 2
Citation - Scopus: 3
Aberrant miR-3135b and miR-1273g-3p Expression in the Peripheral Blood Samples of BRCA1/2 (±) Ovarian Cancer Patients
(Elsevier Ltd, 2024) Tuncer, Seref Bugra); Celik, Betul; Erciyas, Seda Kilic; Erdogan, Ozge Sukruoglu; Pasin, Ozge; Avsar, Mukaddes; Gultaslar, Busra Kurt; Ghafour, Arash Adamnejad; Uyaroglu, Gamze; Odemis, Demet Akdeniz; Yazici, Hulya
Ovarian cancer (OC) ranks as the eighth most prevalent malignancy among women globally. The short non-coding RNA molecules, microRNAs (miRNAs) target multiple mRNAs and regulate the gene expression. Here in this study, we aimed to validate miR-3135b and miR-1273g-3p as novel biomarkers for prognostic and diagnostic factor OC. After RNA isolation, we analyzed the miR-3135b and miR-1273g-3p expression in peripheral blood samples derived from 150 OC patients. Subsequently, we compared their expression levels with 100 healthy controls. The differences of miR-3135b and miR-1273g-3p expression were detected using the Quantitative Real Time-PCR (qRT-PCR) technique following miRNA-specific cDNA synthesis pursing miRNA separation. The miR-3135b and miR-1273g-3p were higher in OC patients who tested positive for BRCA1/2 compared to BRCA-negative patients, and healthy cases. The level of miR-3135b demonstrated a roughly 4.82-fold increase in OC patients in comparison to the healthy cases, while miR-1273g-3p expression exhibited a roughly 6.77-fold increase. The receiver operating characteristic (ROC) analysis has demonstrated the potential of miR-3135b and miR-1273g-3p as markers for distinguishing between OC patients and healthy controls. The higher expressions of miR-3135b and miR-1273g-3p could be associated with OC development. Moreover, miR-3135b may have a diagnostic potential and miR-1273g-3p may have both diagnostic and prognostic potential in OC cell differentiation. The string analysis has revealed an association between miR-1273g-3p and the MDM2 gene, suggesting a potential link to tumor formation through the proteasomal degradation of the TP53 tumor suppressor gene. Additionally, the analysis indicates an association of miR-1273g-3p with CHEK1, a gene involved in checkpoint-mediated cell cycle arrest. String analysis also indicates that miR-3135b is associated with the MAPK1 gene, causing activation of the oncogenesis cascade. In conclusion, miR-1273g-3p, and miR-3135b exhibit significant potential as diagnostic markers. However, further research is needed to comprehensively investigate these miRNAs diagnostic and predictive characteristics in a larger cohort. © 2023 The Authors
Citation - WoS: 1
Citation - Scopus: 1
Germline Mutational Variants of Turkish Ovarian Cancer Patients Suspected of Hereditary Breast and Ovarian Cancer (HBOC) by Next-Generation Sequencing
(Elsevier GmbH, 2024) Tuncer, Seref Bugra; Celik, Betul; Erciyas, Seda Kilic; Erdogan, Ozge Sukruoglu; Gultaslar, Busra Kurt; Odemis, Demet Akdeniz; Avsar, Mukaddes; Sen, Fatma; Saip, Pinar Mualla; Yazici, Hulya
Hereditary Breast and Ovarian Cancer (HBOC) syndrome is characterized by an increased risk of developing breast cancer (BC) and ovarian cancer (OC) due to inherited genetic mutations. Understanding the genetic variants associated with HBOC is crucial for identifying individuals at high risk and implementing appropriate preventive measures. The study included 630 Turkish OC patients with confirmed diagnostic criteria of The National Comprehensive Cancer Network (NCCN) concerning HBOC. Genomic DNA was extracted from peripheral blood samples, and targeted Next-generation sequencing (NGS) was performed. Bioinformatics analysis and variant interpretation were conducted to identify pathogenic variants (PVs). Our analysis revealed a spectrum of germline pathogenic variants associated with HBOC in Turkish OC patients. Notably, several pathogenic variants in BRCA1, BRCA2, and other DNA repair genes were identified. Specifically, we observed germline PVs in 130 individuals, accounting for 20.63% of the total cohort. 76 distinct PVs in genes, BRCA1 (40 PVs), BRCA2 (29 PVs), ATM (1 PV), CHEK2 (2 PVs), ERCC2 (1 PV), MUTYH (1 PV), RAD51C (1 PV), and TP53 (1PV) and also, two different PVs (i.e., c.135–2 A>G p.? in BRCA1 and c.6466_6469delTCTC in BRCA2) were detected in a 34-year-old OC patient. In conclusion, our study contributes to a better understanding of the genetic variants underlying HBOC in Turkish OC patients. These findings provide valuable insights into the genetic architecture of HBOC in the Turkish population and shed light on the potential contribution of specific germline PVs to the increased risk of OC. © 2024 Elsevier GmbH
Structural and Functional Changes in the Brains of Guitarist Musicians: Volumetric, VBM, and Resting State fMRI Study
(Erciyes Univ Sch Medicine, 2024) Acer, Niyazi; Arpacay, Burcu Kamasak; Gray, Serap Bastepe; Karapinar, Burak Oguzhan; Ipekten, Funda; Degirmencioglu, Levent; Ilica, Ahmet Turan
Objective: Musicians acquire intricate motor and auditory skills from an early age, serving as an exemplary model for brain plasticity. This study aimed to investigate the structural and functional differences in the brains between guitar-playing musicians and non-musicians. Materials and Methods: Cortical thickness measurements, volumetric analysis of the corpus callosum and hippocampus, voxel-based morphometry (VBM), and resting-state functional magnetic resonance imaging (fMRI) were applied to a magnetic resonance imaging dataset from 14 male young adult guitar players and 10 matched non-musicians. Results: A structural asymmetry, mainly localized to hippocampal regions including the stratum radiatum, lacunosum, and moleculare, was found in the musicians' group. VBM analysis demonstrated increased volume in the frontal middle and inferior gyri (left), precuneus (right), insula (right), and Brodmann areas 7 and 13 in the musician group compared to non-musicians. There were no statistical differences between musicians and non-musicians in terms of corpus callosum and hippocampal subfield volumes. Although cortical thickness measured at different locations was higher in the musician group than in the non-musician group, these differences were not statistically significant (p>0.05). No significant functional connectivity alterations were found within the default mode network between musicians and non-musicians (p>0.05). Conclusion: Playing a musical instrument triggers rapid integration of multi-sensory information in the context of musical performance. The functional state of rest has contributed significantly to understanding musicians' brain networks.
Citation - WoS: 4
Citation - Scopus: 4
Modulation of Neuronal Damage in DRG By Asprosin in a High-Glucose Environment and Its Impact on miRNA181-a Expression in Diabetic DRG
(Springer, 2024) Adam, Muhammed; Ozcan, Sibel; Dalkilic, Semih; Tektemur, Nalan Kaya; Tekin, Suat; Bilgin, Batuhan; Hekim, Munevver Gizem; Bulut, Ferah; Kelestemur, Muhammed Mirac; Canpolat, Sinan; Ozcan, Mete
Asprosin, a hormone secreted from adipose tissue, has been implicated in the modulation of cell viability. Current studies suggest that neurological impairments are increased in individuals with obesity-linked diabetes, likely due to the presence of excess adipose tissue, but the precise molecular mechanism behind this association remains poorly understood. In this study, our hypothesis that asprosin has the potential to mitigate neuronal damage in a high glucose (HG) environment while also regulating the expression of microRNA (miRNA)-181a, which is involved in critical biological processes such as cellular survival, apoptosis, and autophagy. To investigate this, dorsal root ganglion (DRG) neurons were exposed to asprosin in a HG (45 mmol/L) environment for 24 hours, with a focus on the role of the protein kinase A (PKA) pathway. Expression of miRNA-181a was measured by using real-time polymerase chain reaction (RT-PCR) in diabetic DRG. Our findings revealed a decline in cell viability and an upregulation of apoptosis under HG conditions. However, pretreatment with asprosin in sensory neurons effectively improved cell viability and reduced apoptosis by activating the PKA pathway. Furthermore, we observed that asprosin modulated the expression of miRNA-181a in diabetic DRG. Our study demonstrates that asprosin has the potential to protect DRG neurons from HG-induced damage while influencing miRNA-181a expression in diabetic DRG. These findings provide valuable insights for the development of clinical interventions targeting neurotoxicity in diabetes, with asprosin emerging as a promising therapeutic target for managing neurological complications in affected individuals. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Citation - WoS: 3
Citation - Scopus: 3
Investigation of the Methylation Changes in the Promoter Region of RB1 Gene in Retinoblastoma
(Elsevier GmbH, 2024) Erdogan, Ozge Sukruoglu; Odemis, Demet Akdeniz; Kayim, Zubeyde Yalniz; Gurbuz, Orkun; Tuncer, Seref Bugra; Kilic, Seda; Celik, Betul; Tuncer, Samuray; Bay, Sema Buyukkapu; Kebudi, Rejin; Yazici, Hulya
Retinoblastoma is an infrequent neoplasm that arises during childhood from retinal nerve cells and is attributed to the biallelic inactivation of the RB1 gene. In conjunction with anatomical anomalies, it is widely acknowledged that epigenetic modifications play a significant role in the pathogenesis of cancer. The association between methylation of the RB1 gene promoter and tumor formation has been established; however, there is currently no scholarly evidence to substantiate the claim that it is responsible for the inheritance of retinoblastoma. The initial hypothesis posited for this work was that familial retinoblastoma disease would be similarly observed in cases with RB1 promotor gene methylation, akin to RB1 mutations. The RB1 gene promoter region was subjected to methylation screening using real-time PCR in individuals diagnosed with familial retinoblastoma but lacking RB1 mutations. The study involved a comparison of the germline methylation status of the RB1 gene in the peripheral blood samples of 50 retinoblastoma patients and 52 healthy individuals. The healthy individuals were carefully selected to match the retinoblastoma patients in terms of age, sex, and ethnicity. The data obtained from both groups were subjected to statistical analysis. The study revealed that the methylation level in a cohort of 50 individuals diagnosed with retinoblastoma and 52 healthy control participants was determined to be 36.1% and 33.9%, respectively. As a result, there was no statistically significant disparity observed in RB1 promoter methylation between the patient and control groups (p = 0.126). The methylation of the promoter region of the RB1 gene in familial retinoblastoma does not exert any influence on the hereditary transmission of the disease.
Citation - WoS: 5
Citation - Scopus: 4
Effect of Angiotensin-Converting Enzyme Inhibitor and Angiotensin Receptor Blocker on Oxidative Stress and Metabolism of Elements in Kidney of STZ-Induced Diabetic Rats
(Academic Press Inc., 2024) Ozsobaci, Nural Pastaci; Karatas, Metehan; Tuncdemir, Matem; Ozcelik, Dervis
In diabetes, increased oxidative stress and impaired trace element metabolism play an important role in the pathogenesis of diabetic nephropathy. The objective of this research was to examine the outcomes of blocking the renin-angiotensin system, using either the angiotensin-converting enzyme inhibitor (ACEI), perindopril, or the angiotensin II type 1 (AT1) receptor blocker, irbesartan, on oxidative stress and trace element levels such as Zn, Mg, Cu, and Fe in the kidneys of diabetic rats that had been induced with streptozotocin. Thirty-two Wistar albino male rats were equally divided into four groups. The first group was used as a control. The second group of rats developed diabetes after receiving a single intraperitoneal dose of STZ. The third and fourth groups of rats had STZ-induced diabetes and received daily dosages of irbesartan (15 mg/kg b.w/day) and perindopril (6 mg/kg b.w/day) treatment, respectively. Biochemical analysis of the kidneys showed a distinct increase in oxidative stress, indicated by heightened levels of malondialdehyde (MDA) and decreased superoxide dismutase (SOD) activities, as well as reduced glutathione (GSH) levels in the kidneys of diabetic rats. In the kidneys of diabetic rats, the mean levels of Fe and Cu were found to be significantly higher than those of the control group. Additionally, the mean levels of Zn and Mg were significantly lower in the diabetic rats compared to the control rats. Both perindopril and irbesartan decreased significantly MDA content and increased SOD activities and GSH levels in the kidneys of rats with diabetes. The Zn and Mg concentrations in the kidneys of diabetic rats treated with perindopril and irbesartan were markedly higher than in untreated STZ-diabetic rats, while the Cu and Fe concentrations were significantly lower. The urinary excretion of rats treated with perindopril and irbesartan showed a pronounced increase in Cu levels, along with a significant reduction in Zn and Mg levels. Although diabetic rats demonstrated degenerative morphological alterations in their kidneys, both therapies also improved diabetes-induced histopathological modifications in the kidneys. Finally, the present results suggest that manipulating the levels of Zn, Mg, Cu, and Fe - either through ACE inhibition or by blocking AT1 receptors - could be advantageous in reducing lipid peroxidation and increasing antioxidant concentration in the kidneys of diabetic rats. © 2023 Elsevier Inc.
Citation - WoS: 3
Citation - Scopus: 4
DNA Methylation of KIFC1 Gene in Determination of Histological Diagnosis, Prognosis and Metastasis of Lung Cancer
(Elsevier GmbH, 2023) Celik, Betul; Pasin, Ozge; Sen, Sena; Tuncer, Seref Bugra; Kayim, Zubeyde Yalniz; Erciyas, Seda Kilic; Erdogan, Ozge Sukruoglu; Gultaslar, Busra Kurt; Ghafour, Arash Adamnejad; Yazici, Hulya; Olgac, Necat Vakur
Background: One of the main features of cancer, especially lung cancer (LC), is abnormal cell division. Abnormal expression of kinesin family member C1 (KIFC1/HSET), which is involved in mitotic cell division and ensures equatorial alignment of chromosomes during division, is observed in both premalignant and malignant lesions. There are no studies in the literature addressing the role of KIFC1 in the diagnosis and follow-up of LC. In this study, we investigated the epigenetic role of KIFC1 in the diagnosis, stage, and prognosis of various histological subtypes diagnosed with LC. Material and Methods: The expression and methylation status of the KIFC1 gene were examined after DNA/RNA isolation in tumor, conjugate normal tissue, and blood samples from 39 patients diagnosed with LC and in blood samples from 39 healthy controls. Changes in KIFC1 gene expression were examined by the Quantitative Real Time-PCR (qRT-PCR) method after cDNA synthesis following RNA isolation. The Methylation-Specific PCR (MSP) method was used to determine the methylation status of the KIFC1 gene. In this study, the expression/methylation profiles of the KIFC1 gene and the clinical and pathological characteristics of the patients were analyzed by statistical methods. Result: Hypomethylation was detected in 95.8% of the 62.1% of patients’ tissues with increased KIFC1 gene expression. The expression level of the KIFC1 gene was found to be increased 3.2-fold in the tumor tissues of the patients compared with the conjugated normal tissues and 2.4-fold in the serum of the patients compared with the healthy serum. Statistical comparison of patients' clinical parameters and methylation and expression results revealed statistical significance between KIFC1 expression and metastasis, tumor stage and tumor grade. Conclusion: In conclusion, the increase in the expression level of the KIFC1 gene is higher in patients diagnosed with LC than in the healthy population, and therefore, the increase in the expression level of the KIFC1 gene due to hypomethylation can be used as a screening biomarker in LC. It can also be considered that the methylation profile of the KIFC1 gene may be a potential biomarker for determining the subtype of squamous cell carcinoma in LC. The results of the study need to be analyzed and continued with a larger number of patients. © 2023 Elsevier GmbH
Citation - WoS: 9
RB1 Gene Mutations and Genetic Spectrum in Retinoblastoma Cases
(Lippincott Williams & Wilkins, 2023) Odemis, Demet Akdeniz; Kebudi, Rejin; Bayramova, Jamila; Erciyas, Seda Kilic; Turkcan, Gozde Kuru; Tuncer, Seref Bugra; Erdogan, Ozge Sukruoglu; Celik, Betul; Gultaslar, Busra Kurt; Bay, Sema Buyukkapu; Tuncer, Samuray; Yazici, Hulya
The aim of the study was to investigate the frequency and types of mutations on the retinoblastoma gene (RB1 gene) in Turkish population. RB1 gene mutation analysis was performed in a total of 219 individuals (122 probands with retinoblastoma, 14 family members with retinoblastoma and 83 clinically healthy family members). All 27 exons and close intronic regions of the RB1 gene were sequenced for small deletions and insertions using both the Sanger sequencing or NGS methods, and the large deletions and duplications were investigated using the MLPA analysis and CNV algorithm. The bilateral/trilateral retinoblastoma rate was 66% in the study population. The general frequency of RB1 gene mutation in the germline of the patients with retinoblastoma was 41.9%. Approximately 51.5% of the patients were diagnosed earlier than 12 months old, and de novo mutation was found in 32.4% of the patients. Germline small genetic rearrangement mutations were detected in 78.9% of patients and LGRs were detected in 21.1% of patients. An association was detected between the eye color of the RB patients and RB1 mutations. 8 of the mutations detected in the RB1 gene were novel in the study.
Citation - Scopus: 2
Evaluating the Brainstem in Children with Breathholding Spells
(Kare Publishing, 2022) Ozcora, Gul Demet Kaya; Kumandas, Sefer; Sagiroglu, Ayse; Acer, Niyazi; Doganay, Selim; Yigit, Huseyin; Canpolat, Mehmet; Per, Huseyin; Gumus, Hakan
OBJECTIVE: Breath-holding spells (BHSs) are a non-epileptic paroxysmal phenomenon characterized by frequent apnea episodes, loss of consciousness, and changes in skin tone and postural tone triggered by negative stimuli of childhood. The pathophysiology of the disease remains unclear; autonomic dysregulation caused by delayed myelination is believed to play a role. In this study, we aimed to evaluate the brainstems of children with BHS using diffusion tensor imaging (DTI) and investigate the etiology of this phenomenon. METHODS: The study group consisted of 16 children with a history of severe breath-holding episodes (accompanied by loss of consciousness and tonic contraction due to prolonged anoxic response) and 18 age-, gender-, and handedness-matched controls. All children underwent systemic, neurologic, and cardiologic evaluation, including complete blood count, blood biochemistry, serum iron and ferritin level, serum vitamin B12 level, electrocardiogram, and electroencephalograms. Magnetic resonance imaging was performed using a 1.5-Tesla Siemens Aera scanner (Siemens, Germany). RESULTS: Evaluation of brainstem (midbrain, pons, and medulla oblongata) volumes revealed no statistically significant differences between the BHS patient and control groups. In a voxel-wise analysis of DTI data, the BHS patient group had significantly lower fractional anisotropy (FA) values than the control group in the bilateral midbrain and medulla, right corticospinal tract, bilateral corpus callosum body and splenium, and left corpus callosum genu. In contrast, there were no significant differences in FA values in the pons, cerebellum, left corticospinal tract, and right corpus callosum genu. CONCLUSION: Based on our findings, we think that patients with BHS should be treated with an approach similar to other neurodevelopmental diseases and that this study may help elucidate the pathophysiology and establish the groundwork for future studies on its treatment. © 2022 by Istanbul Provincial Directorate of Health.
Citation - WoS: 1
Citation - Scopus: 1
Histopathological View of Benign Essential Blepharospasm: Orbicularis Oculi Hormone Receptor Levels
(Kare Publ, 2023) Cabuk, Kubra Serefoglu; Coban, Ganime; Cakir, Gulay Yalcinkaya; Serefoglu, Zeynep Sezal; Nacaroglu, Senay Asik; Karabulut, Gamze Ozturk; Fazil, Korhan
Objectives: Benign essential blepharospasm (BEB) is a focal dystonia characterized by involuntary contractions of the orbicularis oculi and periocular muscles. We aimed to investigate the effects of muscle receptor levels on the etiopathogenesis of blepharospasm by evaluating the orbicularis oculi estrogen receptor (ER) and androgen receptor (AR) levels. Methods: Four blepharospasm patients (2 females and 2 males) who underwent upper lid blepharoplasty and/or orbicularis myomectomy and 4 healthy cases (2 females, 2 males) that had upper lid blepharoplasty were included. The pretarsal, preseptal, and orbital parts of the orbicularis muscles of the patients who underwent orbicularis myomectomy and the waste muscle tissue materials taken from the preseptal orbicularis muscles of the patients who had only upper blepharoplasty were analyzed. Immunohistochemical staining was performed with estrogen alpha and androgen. Results: In healthy men, the orbicularis oculi muscle was stained with ER at a moderate intensity and with AR at a high intensity. In men with blepharospasm, the orbicularis oculi were not stained with ER at all, but at a high intensity with AR. In healthy women, the orbicularis oculi were stained with ER and AR at a high intensity (>50%). In women with blepharospasm, the staining intensities of both receptors were moderate. Conclusion: We determined a decrease in ER and AR in females and almost the absence of ER in males with BEB. This decrease in ER may be associated with a functional abnormality in mitochondria and the decrease in hormonal receptors may be associated with sarcopenia in orbicularis oculi muscle fibers.
P323L Mutation in a Case with Prolonged SARS-CoV-2 PCR Positivity
(NLM (Medline), 2023) Yücebağ, Ebru; Arslan, Neşe; Tok, Yeşim; Nohut, Okan Kadir; Salman Yılmaz, Seda; Kuşkucu, Mert Ahmet; Midilli, Kenan
Coronavirus disease-2019 (COVID-19) emerged in the last months of 2019 and caused a pandemic effecting the whole world. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19 has changed by various mutations since the day it was first identified, causing the pandemic to continue. Age, male gender, obesity, and comorbidity, which are general risk factors for COVID-19, can also cause prolonged PCR positivity. In this report, a case of 37-year-old male who is working in the hospital's COVID-19 molecular diagnostics laboratory was presented. He was vaccinated with three doses of inactivated vaccine, CoronaVac (Sinovac Biotech, Beijing-China), within the context of the vaccination program carried out in Türkiye. His first SARS-CoV-2 positivity was detected on 12.01.2021, four months after the last vaccination, and he continued to be detected positive for SARS-CoV-2 throughout a period of 39 days by quantitative reverse transcription polymerase chain reaction (qRT-PCR) tests performed with 2-3-day intervals. The patient has a 20-pack/year smoking history and his body mass index (BMI) was 29.8 kg/m2 at the time of his COVID-19. The case, which was clinically defined as mild COVID-19 with symptoms including back and headache, cough, fever (38.5°C), and loss of taste-smell, and without any additional complications or respiratory distress during the disease process. In the radiological examination, the lung was found within normal ranges. Prophylactic enoxaparin sodium anti-xa IU/0.6 ml was administered to the patient due to his cardiovascular risk, and no additional treatment was given. Whole genome sequencing was performed from nasopharyngeal swab samples of the patient at the beginning and 16th day of the infection to investigate the the specific genomic features and mutation pattern of the virus in the host over time, due to the prolonged SARS-CoV-2 PCR positivity. Library preparation for the whole next-generation sequencing (NGS) was performed by the SARS-CoV-2 Panel, Paragon CleanPlex kit (Paragon Genomics, USA), and indexing of the library was done by Clean-Plex Dual-Indexed PCR Primers for Illumina Set B kit (Paragon Genomics, USA). NGS analysis was performed on the Illumina Miniseq (Illumina, USA) platform. As a result of the bioinformatics evaluation, both samples were determined as SARS-CoV-2 Delta variant (Nextclade; 21J-Delta variant, Pango lineage; AY.43). Remarkably, the SARSCoV-2 sequences in the two samples taken 15 days apart; several identical mutations; such as D614G in the S gene, P323L in the ORF 1b gene region, and P1228L in the Nsp3 gene region, were detected. Besides that, when compared to the first sample, three additional mutations (P383L, P539S, L838I) were observed in the sequence of the second sample, which led to three amino acid changes, the clinical significance of which has not yet been determined in the literature. It is thought that; these mutations that change amino acid expression, as well as the other three mutations detected, may contribute to the improvement of the fitness of the virus and may be one of the factors responsible for the prolonged SARS-CoV-2 PCR positivity. Additional data to be obtained by further epidemiological sequencing studies will shed light on this issue.
Citation - WoS: 152
Tuberous Sclerosis Complex and Cancer
(Istanbul Tip Fakultesi, 2023) Doğan, T.; Yazici, H.
Tuberous sclerosis complex (TSC) is a neurocutaneous syndrome that can affect multiple organ systems such as the brain, heart, and lung, and neurological disorders such as autism spectrum disorder and mental retardation can be observed along with epileptic seizures in affected individuals. The disease can occur at any age. A genetic disease of TSC develops due to the mutations in TSC1 and TSC2 genes that cause dysfunction in Tuberin and/or Hamartin proteins. Although the disease has a highly variable penetrance, the cellular signal transduction mechanisms of TSC-related genes have largely been elucidated. The diagnostic criteria created by International TSC Consensus Group in 2012 are used in the diagnosis of the syndrome in addition to the genetic tests. At present, it is estimated that there are approximately 2 million people with TSC worldwide and 50,000 people are affected by the disease in the USA alone. It is important to know about the molecular genetics and clinical features of the disease for targeted therapies and well-managed surveillance. In the present study, we aimed to examine the genetic, biological, and clinical features of TSC and to discuss the genetic counseling approach that should be applied to patients with TSC. © 2023, Turkish Society for Radiation Oncology.
Examination of Brain-Derived Neurotrophic Factor, Glial Cell Line-Derived Neurotrophic Factor, and Neurotrophin-3 Levels and Brain Volumes in Shift-Working Men: Clinical Research
(Turkiye Klinikleri, 2023) Balcioğlu, Mücahide Büşra; Kuzay Aksoy, Dilek; Tutal Gürsoy, Görkem; Oğuz Firat, Esra; Tuna, Elvan Evrim; Acer, Niyazi
Objective: This study aims to examine the levels of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) and brain volumes in shift-working men. Material and Methods: Forty-nine men who have been working in shifts for at least 1 year were included in the study. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep quality, Montreal Cognitive Assessment (MoCA) test and trail making test (TMT) were used to assess cognitive performance, and Beck Anxiety Inven-tory (BAI) was used to assess anxiety level. Afterwards, plasma BDNF, GDNF and NT-3 levels were examined. Brain volume measurement was performed. Re-sults: Since the PSQI results of shift-working men were above 5, it was determined that they had “poor sleep quality”. According to the BAI results, 85% of them had anxiety. Primary-secondary school graduate shift-working men had lower MoCA value and TMT-A and TMT-B test scores were higher (p<0.05). Working in shifts for 6 years or more caused a significant decrease in BDNF and NT-3 levels (p<0.05). According to the correlation analysis results, it was observed that the prefrontal cortex, dorsolateral prefrontal cortex and cerebral cortex in the left lobe of the brain were smaller in elderly shift workers (p[removed]
Citation - Scopus: 14
Impact of Cerebral Microbleeds in Stroke Patients with Atrial Fibrillation
(John Wiley and Sons Inc, 2023) Soo, Yannie; Zietz, Annaelle; Yiu, Brian; Mok, Vincent C. T.; Polymeris, Alexandros A.; Seiffge, David; Ambler, Gareth; Wilson, Duncan; Leung, Thomas Wai Hong; Tsang, Suk Fung; Chu, Winnie; Abrigo, Jill; Orken, Dilek Necioglu
Objectives: Cerebral microbleeds are associated with the risks of ischemic stroke and intracranial hemorrhage, causing clinical dilemmas for antithrombotic treatment decisions. We aimed to evaluate the risks of intracranial hemorrhage and ischemic stroke associated with microbleeds in patients with atrial fibrillation treated with vitamin K antagonists, direct oral anticoagulants, antiplatelets, and combination therapy (i.e. concurrent oral anticoagulant and antiplatelet). Methods: We included patients with documented atrial fibrillation from the pooled individual patient data analysis by the Microbleeds International Collaborative Network. Risks of subsequent intracranial hemorrhage and ischemic stroke were compared between patients with and without microbleeds, stratified by antithrombotic use. Results: A total of 7,839 patients were included. The presence of microbleeds was associated with an increased relative risk of intracranial hemorrhage (adjusted hazard ratio [aHR] = 2.74, 95% confidence interval = 1.76–4.26) and ischemic stroke (aHR = 1.29, 95% confidence interval = 1.04–1.59). For the entire cohort, the absolute incidence of ischemic stroke was higher than intracranial hemorrhage regardless of microbleed burden. However, for the subgroup of patients taking combination of anticoagulant and antiplatelet therapy, the absolute risk of intracranial hemorrhage exceeded that of ischemic stroke in those with 2 to 4 microbleeds (25 vs 12 per 1,000 patient-years) and ≥ 11 microbleeds (94 vs 48 per 1,000 patient-years). Interpretation: Patients with atrial fibrillation and high burden of microbleeds receiving combination therapy have a tendency of higher rate of intracranial hemorrhage than ischemic stroke, with potential for net harm. Further studies are needed to help optimize stroke preventive strategies in this high-risk group. ANN NEUROL 2023. © 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.