Browsing by Author "Ergören, Mahmut Çerkez"

Now showing 1 - 14 of 14

A homozygous synonymous variant likely cause of severe ciliopathy phenotype
(MDPI, 2021-06-01) Tuncel, Gülten; Kaymakamzade, Bahar; Engindereli, Yeliz; Temel, Şehime Gülsün; Ergören, Mahmut Çerkez; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Translasyonel Tıp Anabilim Dalı; 0000-0002-9802-0880; AAG-8385-2021
Joubert syndrome (OMIM #213300) is a rare neurodevelopmental disease characterized by abnormal breathing patterns, intellectual impairment, ocular findings, renal cysts, and hepatic fibrosis. It is classified as a ciliopathy disease, where cilia function or structure in various organs are affected. Here, we report a 17-year-old male whose main clinical findings are oculomotor apraxia and truncal ataxia. Magnetic resonance imaging revealed the characteristic molar tooth sign of Joubert syndrome. He also has obsessive-compulsive disorder concomitantly, which is not a known feature of Joubert syndrome. Molecular genetic analysis revealed a homozygous c.2106G>A (p.(Thr702=)) variation in the Abelson helper integration 1 (AHI1) gene and another homozygous c.1739C>T (p.Thr580Ile) variation in the coiled-coil and C2 domain-containing protein 1A (CC2D1A) gene. Even though certain AHI1 variations were previously associated with Joubert syndrome (JS), c.2106G>A (p.(Thr702=)) was only reported in one patient in trans with another known pathogenic JS variant. The CC2D1A c.1739C>T (p.Thr580Ile) variation, on the other hand, has been reported to cause autosomal recessive nonsyndromic mental retardation, but there are conflicting interpretations about its pathogenicity. Overall, to our knowledge, this is the first patient representing a severe ciliopathy phenotype caused by a homozygous synonymous AHI1 variation. Further investigations should be performed to determine any involvement of the CC2D1A gene in ciliopathy phenotypes such as Joubert syndrome.
A rare case of fructose-1,6-bisphosphatase deficiency: A delayed diagnosis story
(Walter De Gruyter Gmbh, 2020-10-01) Tuncel, Gulten; Ergören, Mahmut Çerkez; Sag, Sebnem Ozemri; ÖZEMRİ SAĞ, ŞEBNEM; Temel, Sehime Gulsun; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Tıp Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; 0000-0002-9802-0880; AAH-8355-2021; AAG-8385-2021
Objectives: Fructose-1,6-bisphosphatase deficiency (FBPase deficiency, OMIM 229700) is an early-onset rare genetic disorder caused by mutations in the FBP1 gene.Case presentation: Our patient was 17-years-old when she was diagnosed with the disease. Initial sequencing analysis with Ion Torrent technology failed to detect the gross deletion that covered complete exon 2 (c.-24-26_170 + 5192del) of FBP1 gene and caused the delay in diagnosis. Deletion was then detected when sequencing was performed in an Illumina MiSeq platform.Conclusions: This case emphasizes the importance of sequencing data analysis for precise diagnosis of rare diseases and therapy planning.
The association between the chromosome 9p21 CDKN2B-AS1 gene variants and the lipid metabolism: A pre-diagnostic biomarker for coronary artery disease
(Aves, 2019-01) Ergören, Mahmut Çerkez; Temel, Şehime Gülsün; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Temel Tıp Bilimleri/Histoloji ve Embriyoloji Bölümü.; 0000-0001-9593-9325; 0000-0001-9593-9325; 0000-0002-9802-0880; D-8491-2018; AAZ-6885-2021; GQP-2509-2022; AAG-8385-2021; 6507885442; 56731124900
Objective: Recent genome-wide association studies have established that polymorphisms within CDKN2B-ASI of chr9p21.3 locus increased susceptibility to coronary artery disease (CAD) or myocardial infarction. Common variants of CDKN2B-AS1 (including rs4977574 A>G and rs1333040 C>T) are determined to be directly associated with CADs in many populations worldwide and suggested biomarkers for the early detection of CAD. There is a lack of investigation for the association between CDKN2B-AS1 rs4977574 A>G and rs1333040 C>T genetic modifiers and CAD in a Turkish Cypriot population. The aim of the present study was to investigate the potential effects of these variants on susceptibility to developing CAD in a Turkish Cypriot population and their contribution to lipid metabolism. Methods: Seventy-one patients with angiography-confirmed CAD were recruited to the CAD group, whereas 153 voluntary subjects without CAD symptoms were enrolled to the control group. Genotyping for the CDKN2B-AS1 gene polymorphisms was performed by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Results: There is no statistical significant association observed between rs4977574 and rs1333040 single-nucleotide polymorphisms and two studied groups [odds ratio (OR): 0.763, p=0.185, 95% confidence interval (CI): 0.511-1.139 and OR: 1.060, p=0.802, 95% CI: 0.672-1.671, respectively]. However, rs2977574 G and rs1333040 T alleles-the risk alleles-were found to be associated with higher level of serum total cholesterol and lower level of high-density lipoprotein-cholesterol in the CAD group (p=0.019, p=0.006 and p=0.022, p=0.031, respectively). To our knowledge, this is the first study that establishes the effect of rs1333040 on lipid metabolism. Conclusion: The presence of rs4977574 G and rs1333040 T alleles and interaction may exist as environmental factors associated with lipid metabolism and might be responsible for the development of CAD in a Turkish Cypriot population.
Contribution of genotypes in Prothrombin and Factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia
(Wiley, 2023-02-01) Kiraz, Aslıhan; Sezer, Özlem; Alemdar, Adem; Canbek, Sezin; Duman, Nilgün; Bişgin, Atıl; Cora, Tülin; Ruhi, Hatice Ilgın; Ergören, Mahmut Çerkez; Geçkinli, Bilgen Bilge; Sağ, Şebnem Özemri; Gözden, Hilmi Erdem; Öz, Özlem; Altıntaş, Zühal Mert; Yalçıntepe, Sinem; Keskin, Adem; Tak, Ayşegüel Yabacı; Paskal, Şeyma Aktaş; Yürekli, Uğur Fahri; Demirtaş, Mercan; Evren, Emine Ünal; Hanta, Abdullah; Başdemirci, Müeşerref; Süer, Kaya; Balta, Burhan; Kocak, Nadir; Karabulut, Halil Guerhan; Çobanoğulları, Havva; Ateş, Esra Arslan; Bozdoğan, Sevcan Tuğ; Eker, Damla; Ekinci, Sadiye; Nergiz, Sueleyman; Tuncali, Timur; Yagbasan, Serap; Alavanda, Ceren; Kutlay, Nuket Yurur; Evren, Hakan; Erdogan, Murat; Altiner, Sule; Sanlidag, Tamer; Gonen, Gizem Akinci; Vicdan, Arzu; Eras, Nazan; Eker, Hatice Kocak; Balasar, Özgür; Tuncel, Gulten; Dündar, Munis; Gürkan, Hakan; ALEMDAR, ADEM; ÖZEMRİ SAĞ, ŞEBNEM; TEMEL, ŞEHİME GÜLSÜN; Gozden, Hilmi Erdem; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Translasyonel Tıp Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; ELA-3536-2022; IYV-1877-2023; JMQ-2372-2023; IRT-7350-2023
Thrombotic and microangiopathic effects have been reported in COVID-19 patients. This study examined the contribution of the hereditary thrombophilia factors Prothrombin (FII) and Factor V Leiden (FVL) genotypes to the severity of COVID-19 disease and the development of thrombosis. This study investigated FII and FVL alleles in a cohort of 9508 patients (2606 male and 6902 female) with thrombophilia. It was observed that 930 of these patients had been infected by SARS-CoV-2 causing COVID-19. The demographic characteristics of the patients and their COVID-19 medical history were recorded. Detailed clinical manifestations were analyzed in a group of cases (n = 4092). This subgroup was age and gender-matched. FII and FVL frequency data of healthy populations without thrombophilia risk were obtained from Bursa Uludag University Medical Genetic Department's Exome Databank. The ratio of males (31.08%; 27.01%) and the mean age (36.85 & PLUSMN; 15.20; 33.89 & PLUSMN; 14.14) were higher among COVID-19 patients compared to non-COVID-19 patients. The prevalence of FVL and computerized tomography (CT) positivity in COVID-19 patients was statistically significant in the thrombotic subgroup (p < 0.05). FVL prevalence, CT positivity rate, history of thrombosis, and pulmonary thromboembolism complication were found to be higher in deceased COVID-19 patients (p < 0.05). Disease severity was mainly affected by FVL and not related to genotypes at the Prothrombin mutations. Overall, disease severity and development of thrombosis in COVID-19 are mainly affected by the variation within the FVL gene. Possible FVL mutation should be investigated in COVID-19 patients and appropriate treatment should be started earlier in FVL-positive patients.
Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy
(Elsevier Science, 2020-09-18) Ergören, Mahmut Çerkez; Çobanoğulları, Havva; Mocan, Gamze; Temel, Şehime Gülsün; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; 0000-0002-9802-0880; AAG-8385-2021; 6507885442
Personalized medicine holds promise to tailor the treatment options for patients' unique genetic make-up, behavioral and environmental background. Liquid biopsy is non-invasive technique and precise diagnosis and treatment approach. Significantly, NGS technologies have revolutionized the genomic medicine by novel identifying SNPs, indel mutations in both coding and non-coding regions and also a promising technology to accelerate the early detection and finding new biomarkers for diagnosis and treatment. The number of the bioinformatics tools have been rapidly increasing with the aim of learning more about the detected mutations either they have a pathogenic role or not. EGFR, ROS1 and ALK genes are members of the RTK family. Until now, mutations within these genes have been associated with many cancers and involved in resistance formation to TKIs. This review article summarized the findings about the mostly investigated variations in EGFR, ROS1 and ALK genes and their potential role in liquid biopsy approach.
Identification of a novel mitochondrial dna sequence variation within the human mitochondrial dna control region in a population of aegean population
(Erciyes Üniversitesi, 2019-06-01) Köseler, Aylin; Temel, Şehime Gülsün; Ergören, Mahmut Çerkez; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Tarih Bilimi Bölümü ve Embriyoloji; Bursa Uludağ Üniversite/Tıp Fakültesi/Tıp Bölümü Genetik; 0000-0002-9802-0880; AAG-8385-2021
Objective: Environmental impacts, history as well as established cultural regulations, and many more other factors had shaped broadly diverse structure of human genetic patterns. A control region of human mtDNA has served as a good genetic determination marker in many fields such as evolutionary studies and forensic genetics. The allelic variations of mtDNA have been studied in many populations including Turkish populations. Previous studies in Turkish populations lacked large cohorts. In this study, non-coding hypervariable regions of human mitochondrial DNA with extended population of Turkish individuals from Aegean region have been investigated.Materials and Methods: To detect sequence variants in human mtDNA control region, 100 unrelated Turkish subjects were examined.Results: The outcomes revealed 13 variable sites in hypervariable region I (HVRI) and 20 variable sites in hypervariable region II (HVRII). Polymorphisms within HVRI were detected at the positions of 16173 (C>A) and 16175 (A>G) with the allelic variation frequencies of 53% and 60%, respectively. A novel nucleotide transversion from cytosine to adenine at 16173 position was detected. Only 35% of subjects were aligned with the Cambridge Reference Sequence for the poly-cytosine tract that locates between 303 and 309 nucleotides, whereas 60% of individuals had 8 and 15% of them had 10 cytosine polynucleotides. 263G and 73G polymorphisms were evaluated with higher frequencies for the HVSII region.Conclusion: Overall, results indicate that the determination of genotype distributions and allelic variations frequencies of human mitochondrial genome are significant to characterize admixture populations from different ethnic origins.
Inconsistency of karyotyping and array comparative genomic hybridization (acgh) in a mosaic turner syndrome case
(Thieme Medical Publ Inc, 2021-02-11) Tülay, Pınar; Ergören, Mahmut Çerkez; Alkaya, Ahmet; Yaycı, Eyüp; Temel, Şehime Gülsüm; TEMEL, ŞEHİME GÜLSÜN; ÖZEMRİ SAĞ, ŞEBNEM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Anabilim Dalı.; 0000-0002-9802-0880
Purpose Turner syndrome is a sex chromosomal aberration where majority of the patients have 45,X karyotype, while several patients are mosaic involving 45,X/46,XX; 46,X,i(Xq); and other variants. Cytogenetic analysis, karyotyping, is considered to be the "gold standard" to detect numerical and structural chromosomal abnormalities. In the recent years, alternative approaches, such as array comparative genomic hybridization (aCGH), have been widely used in genetic analysis to detect numerical abnormalities as well as unbalanced structural rearrangements. In this study, we report the use of karyotyping as well as aCGH in detecting a possible Turner syndrome variant.Methods An apparent 16-year-old female was clinically diagnosed as Turner syndrome with premature ovarian failure and short stature. The genetic diagnosis was performed for the patient and the parents by karyotyping analysis. aCGH was also performed for the patient.Main Findings Cytogenetic analysis of the patient was performed showing variant Turner syndrome (46,X,i(X)(q10)[26]/46,X,del(X)(q11.2)[11]/45,X[8]/46,XX[5]). The patient's aCGH result revealed that she has a deletion of 57,252kb of Xp22.33-p11.21 region; arr[GRCh37] Xp22.33-p11.21 (310,932-57,563-078)X1. Both aCGH and fluorescence in situ hybridization (FISH) results suggested that short stature Homeobox-containing ( SHOX ) gene, which is located on Xp22.33, was deleted, though FISH result indicated that this was in a mosaic pattern.Conclusion In the recent years, aCGH has become the preferred method in detecting numerical abnormalities and unbalanced chromosomal rearrangements. However, its use is hindered by its failure of detecting mosaicism, especially low-level partial mosaicism. Therefore, although the resolution of the aCGH is higher, the cytogenetic investigation is still the first in line to detect mosaicism.
Investigation of KCNQI polymorphisms as biomarkers for cardiovascular diseases in the Turkish Cypriots for establishing preventative medical measures
(Elsevier, 2019-03-01) Tülay, P.; Ergören, Mahmut Çerkez; Temel, Şehime Gülsün; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Anabilim Dalı.; AAG-8385-2021
Potassium channels are important in transmitting electrical signals through potassium ions transport. These potassium channels are made from signals encoded by KCNQ1 gene. KCNQ1 polymorphisms were associated with many diseases, including many metabolic and cardiovascular diseases and therefore they can be employed as biomarkers. In this study we aimed to investigate KCNQ1 polymorphisms in the Turkish Cypriot population to reveal the allele frequencies specific for this population and use these polymorphisms as biomarkers to develop preventative medical measures.The genotypes of KCNQ1 polymorphisms (rs231361, rs231359, rs151290, rs2283228, rs2237895, rs2237896) were investigated for the first time in Turkish Cypriot population. The correlation between genotypes of these polymorphisms and plasma lipid levels in this population was also explored.The results of this study showed that there was significant differences of the allele frequencies of between rs2283228 allele of C and rs2237896 (P > 0.05) in Turkish Cypriot population. There was no association between the genotypes of the six polymorphisms and the lipid metabolism. This study is the first genetic epidemiology study that investigated the allelic frequencies of KCNQ1 polymorphisms associated with metabolic syndromes as well as cardiovascular diseases.This study proves to be crucial since the etiologic determinants and molecular pathology of cardiovascular diseases have not yet clearly understood. This study showed that genome wide association studies should be designed for preventative medicine in the Turkish Cypriot population.
Letter to the editor regarding the article “A case of hypertrophic and dilated cardiomyopathic sudden cardiac death: De novo mutation in TTN and SGCD genes”
(Kare Yayıncılık, 2017-01) Ergören, Mahmut Çerkez; Temel, Şehime Gülsün; Uludağ Üniversitesi/Tıp Fakültesi/Embriyoloji ve Histoloji Anabilim Dalı.; 0000-0002-9802-0880; AAG-8385-2021; 6507885442
We recently read the article entitled “A case of hypertrophic and dilated cardiomyopathic sudden cardiac death: de novo mutation in TTN and SGCD genes” by Baydar et al. (1) published in the Anatolia Journal of Cardiology in late 2016 with great interest. We commend the authors for their contribution to improving our understanding of sudden cardiac death mechanisms and suggesting potential reasons for occurrence of the condition of genetic origin. We do, however, have a number of thoughts about the study, which are outlined below. The authors mentioned de novo mutation in the sarcoglycan (SGCD) and titin (TTN) genes. The article fails to mention, however, the parent-based variant approach to analysis. In human genetic diseases, the term “de novo mutation” by definition refers to an alteration in a gene that is present for the first time in one family member as a result of a mutation in a germ cell of one of the parents or in the zygote itself. It is only by analyzing the parents that their true contribution to the disease burden can be proven.
Mutation status and immunohistochemical correlation of egfr mutations in gastric cancer patients
(Elsevier, 2019-11-15) Özkayalar, Hanife; Ergören, Mahmut Çerkez; Mocan, Gamze; TEMEL, ŞEHİME GÜLSÜN; Kurt, Serdar; Çevik, Eda; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Anabilim Dalı.; 0009-0005-7240-7664; 0000-0002-9802-0880; AAG-8385-2021; AAZ-6885-2021; GQP-2509-2022
Natural selection at work? Vitamin d deficiency rates and rising health problems in young Turkish cypriot professionals
(Natl Inst Public Health, 2021-01-01) Kandemiş, Emine; Tuncel, Gülten; Fahrioğlu, Ümut; Temel, Şehime Gülsün; Mocan, Gamze; Ergören, Mahmut Çerkez; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; AAG-8385-2021
Objectives: Vitamin D is a fat-soluble, prohormone vitamin that is important especially for bone mineralization and skeletal health. In recent years, vitamin D deficiency appeared as a worldwide problem, affecting many people in different ways including the Northern Cypriot population. The deficiency might be caused by the lack of exposure to sunlight, diet low in vitamin D, sedentary lifestyle, and also due to some genetic variations in the vitamin D receptor (VDR) gene.Methods: In this study, four common VDR polymorphisms and associations with vitamin D deficiency in the Turkish Cypriot population between ages 18-40 and working in office conditions was studied by PCR-RFLP analysis.Results: rs2228570 C>T variant was shown to be significantly associated with low serum vitamin D levels in the studied population.Conclusion: Together with the effect of rs2228570 C>T variant in the VDR gene, it is thought that the lifestyle changes in the Turkish Cypriot population might have caused the increased frequency of vitamin D deficiency in the young professionals.
Strong association between VDR FokI (rs2228570) gene variant and serum vitamin D levels in Turkish Cypriots
(Springer, 2019-06) Tuncel, Gülten; Ergören, Mahmut Çerkez; Temel, Şehime Gülsün; Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Bölümü.; 0000-0002-9802-0880; AAG-8385-2021; 6507885442
Vitamin D is an important molecule to keep teeth, bones and muscles healthy. It is obtained from diet, supplements and primarily from exposure to sunlight. In recent years, vitamin D deficiency is recognised as a worldwide health problem, which results in disturbances in mineral metabolism and skeletal problems. Deficiency might be caused due to sedentary lifestyle, insufficient diet, age as well as some polymorphisms in the VDR gene. In this study the four most common VDR polymorphisms (rs1544410 (BsmI), rs731236 (TaqI), rs7975232 (ApaI) and rs2228570 (FokI)) are investigated in a cohort of Turkish Cypriots and aimed to detect any possible links between low serum vitamin D levels and these variants. The rs2228570 (FokI) variant but not others were shown to have a significant association with decreased serum vitamin D levels in the Turkish Cypriot population.
The use of ACE INDEL polymorphism as a biomarker of coronary artery Chock disease (CAD) in humans with Mediterranean-style diet
(Elsevier, 2019-02-15) Temel, Şehime Gülsün; Ergören, Mahmut Çerkez; Yılmaz, İzel; Oral, Haluk Barbaros; TEMEL, ŞEHİME GÜLSÜN; Yılmaz, İzel; ORAL, HALUK BARBAROS; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Tıbbi İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İmmünoloji Anabilim Dalı.; 0000-0002-9802-0880; 0000-0002-1918-2516; AAG-8385-2021; JSK-9450-2023; K-7285-2012
The ACE INDEL gene polymorphisms are strongly associated with CAD. Therefore, the present study was undertaken to investigate the relationship between ACE INDEL polymorphism and CAD in Turkish Cypriots whose are expected to have Mediterranean-style diet. 273 Turkish Cypriot descent volunteer subjects (186 controls and 87 CAD patients) participated in this study. Genotyping for the ACE INDEL polymorphism was performed by PCR-RFLP analysis. Biochemical parameters except the glucose and triglyceride lipid level were all within normal limits. Glucose level was found significant (p = 0.019) and triglyceride level was observed at the borderline for significance (p = 0.050) in participants according to WHO guidelines. With the respect to the genotype and allele distributions of ACE INDEL, the results showed statistically significant in CAD patients (p = 0.034) and not significant (p = 0.190) in controls. Haplotype analysis showed that D allele was more frequent in patients compared to controls. Thus, there is a statistically significant association with CAD disease with DD genotypes (p = 0.030) in Turkish Cypriot population.The results indicated that ACE INDEL polymorphism is an important predictor of coronary artery disease in Turkish Cypriots. Although 47% of the studied Turkish Cypriot population carry the D allele (p = 0.07), protocols should be developed for prevention strategies immediately. (C) 2018 Elsevier B.V. All rights reserved.
Unique combination and in silico modeling of biallelic POLR3A variants as a cause of Wiedemann–Rautenstrauch syndrome
(Springernature, 2020-12) Ergören, Mahmut Çerkez; Manara, Elena; Paolacci, Stefano T; Tuncel, Gülten; Gül, Şeref; Bertelli, Matteo; Temel, Şehime Gülsün; Uludağ Üniversitesi/Tıp Fakültesi/Temel Tıp Bilimleri Bölümü.; AAG-8385-2021; 6507885442
Neonatal progeroid syndrome or Wiedemann-Rautenstrauch syndrome (WRS; MIM 264090) is a rare genetic disorder that has clinical symptoms including premature aging, lipodystrophy, and variable mental impairment. Until recently genetic background of the disease was unclear. However, recent studies have indicated that WRS patients have compound heterozygote variations in thePOLR3A(RNA polymerase III subunit 3A; MIM 614258) gene that might be responsible for the disease phenotype. In this study we report a WRS patient that has compound heterozygote variations in thePOLR3Agene. One of the reported variations in our patient, c.3568C>T, p.(Gln1190Ter), is a novel variation that was not reported before. The other variant, c.3337-11T>C, was previously shown in WRS patients in trans with other variations.