Browsing by Author "Sağ, Şebnem Özemri"

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A fertile patient with 45X/47XXX mosaicism
(Medecine Et Hygiene, 2015-01-01) Şahintürk, Serdar; Sağ, Şebnem Özemri; Türe, Mehmet; Görükmez, Orhan; Topak, Ali; Yakut, T.; Gülten, T.; ŞAHİNTÜRK, SERDAR; ÖZEMRİ SAĞ, ŞEBNEM; Türe, Mehmet; Görükmez, Orhan; Topak, Ali; Yakut, T.; Gülten, T.; Uludağ Üniversitesi/Tıp Fakültesi/Genetik Bölümü; 0000-0002-9241-0896; ACQ-9887-2022; AAH-8355-2021; HNQ-2791-2023; ECY-8582-2022; FZW-2060-2022; GIS-1493-2022; EYU-9227-2022
A fertile patient with 45X/47XXX mosaicism: Turner syndrome (TS) is a sex chromosome abnormality with a frequency of 1/2,000-3,000 among female live births. Characteristic findings are short stature and gonadal dysgenesis. Short and webbed neck, low posterior hairline, broad chest, widespread nipples, cubitus valgus, short 4th and 5th metacarpals, multiple pigmented nevi, primary amenorrhea, lack of secondary sexual characteristics, cardiovascular and renal anomalies are the most common presentations. Most of the cases are infertile. Spontaneous pregnancy is unusual and the risk for congenital anomaly, spontaneous abortion, stillbirth and aneuploidy is increased. Fifty percent of the patients have classical monosomy X (45,X). However mosaicism of 45,X/47,XXX is rare and accounts for 1.7% of the TS cases. Some cases may not reflect the characteristic phenotype. Some cases with normal height, normal menstrual cyclus and fertility have been defined before. The case we present herein is a 26 years old woman who was admitted to our clinic due to recurrent pregnancy loss. In her medical history she had type 1 diabetes mellitus and endometrium cancer, in her family history her mother had recurrent pregnancy loss. The patient's first, third, fourth, fifth and sixth pregnancies had resulted in spontaneous abortions in the first trimester. She had a healthy daughter with 46,XX karyotype from her second pregnancy. A 45,X[8]/47,XXX[12] karyotype was detected by conventional cytogenetic analysis of the patient who did not have dysmorphic findings. The mosaicism was confirmed by FISH analysis with CEP X probe. Of the 100 cells evaluated, 65 of them had 3 signals of X chromosome while 35 had 1 signal. We present the case because of its scarcity in the literature.
Ailevi Akdeniz ateşi tanısı olan hastalarda Ekzon 10 lokasyonunda mutasyon pozitifliğinin klinik ve laboratuvar yansıması
(2024-04-03) Ocak, Tuğba; Görünen, Ahmet; Yağız, Burcu; Coşkun, Belkıs Nihan; Sağ, Şebnem Özemri; Dalkılıç, Hüseyin Ediz; Yavuz Pehlivan; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı; Bursa Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı/Romatoloji Bilim Dalı; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı; 0000-0002-4560-1569; 0000-0002-7745-8226; 0000-0002-0624-1986; 0000-0003-0298-4157; 0000-0002-3948-8889; 0000-0001-8645-2670; 0000-0002-7054-5351
Ailevi Akdeniz Ateşi (AAA) 10 ekzondan oluşan Mediterranean Fever (MEFV) geninde meydana gelen mutasyonlar sonucu tekrarlayan ateş ve serözit ataklarıyla seyreden otoinflamatuar bir hastalıktır. Ekzon 10 lokasyonunda mutasyon pozitifliği tipik klinik fenotiple ve amiloidoz, böbrek yetmezliği gibi hastalık komplikasyonlarıyla ilişkilidir. Çalışmamızda 10. ekzonda mutasyon varlığının klinik özellikler ve komplikasyonlar ile ilişkisini saptamayı amaçladık. Hastanemiz romatoloji kliniğinde Ocak 2015-Ağustos 2023 tarihleri arasında AAA tanısı ile takip edilen 354 hastanın dosyası retrospektif olarak incelendi. Hastalar ekzon 10 lokasyonunda mutasyon bulunma durumuna göre iki gruba ayrıldı. Ekzon 10’da mutasyon pozitifliği olan grupta erkek cinsiyet oranı, karın ağrısı, amiloidoz görülme sıklığı, ataksız dönemdeki kreatinin, nötrofil ve c-reaktif protein değerleri anlamlı olarak daha yüksek saptandı (sırasıyla p=0,044, p=0,039, p<0.001, p=0,028, p=0,015, p=0,030). Ekzon 10 lokasyonunda mutasyon pozitifliği olan hastalarda klinik ve laboratuvar özellikler farklılık göstermekte olup, bu hastaların yakın takip edilmesi ile hastalıkla ilişkili kompikasyonlar azaltılabilir.
Alzheimer disease associated loci: APOE single nucleotide polymorphisms in Marmara Region
(MDPİ, 2024-05-01) Ismail, Aya Badeea; Dundar, Mehmet Sait; Erguzeloglu, Cemre Ornek; Ergoren, Mahmut Cerkez; Alemdar, Adem; Sag, Sebnem Ozemri; Temel, Sehime Gulsun; Alemdar, Adem; ALEMDAR, ADEM; Sağ, Şebnem Özemri; ÖZEMRİ SAĞ, ŞEBNEM; Temel, Şehime Gülsün; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.
Alzheimer's disease (AD) is a major global health challenge, especially among individuals aged 65 or older. According to population health studies, Turkey has the highest AD prevalence in the Middle East and Europe. To accurately determine the frequencies of common and rare APOE single nucleotide polymorphisms (SNPs) in the Turkish population residing in the Marmara Region, we conducted a retrospective study analyzing APOE variants in 588 individuals referred to the Bursa Uludag University Genetic Diseases Evaluation Center. Molecular genotyping, clinical exome sequencing, bioinformatics analysis, and statistical evaluation were employed to identify APOE polymorphisms and assess their distribution. The study revealed the frequencies of APOE alleles as follows: epsilon 4 at 9.94%, epsilon 2 at 9.18%, and epsilon 3 at 80.68%. The gender-based analysis in our study uncovered a tendency for females to exhibit a higher prevalence of mutant genotypes across various SNPs. The most prevalent haplotype observed was epsilon 3/epsilon 3, while rare APOE SNPs were also identified. These findings align with global observations, underscoring the significance of genetic diversity and gender-specific characteristics in comprehending health disparities and formulating preventive strategies.
An endocrinological perspective on 22q11.2 deletion syndrome: A single-center experience
(Galenos Publ House, 2023-09-01) DENKBOY ÖNGEN, YASEMİN; EREN, ERDAL; ÖZEMRİ SAĞ, ŞEBNEM; Sağ, Şebnem Özemri; Eren, Erdal; Temel, Şehime Gülsüm; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Pediatri Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 0000-0002-1684-1053; KHZ-1491-2024; JPK-3909-2023
Objective: 22q11.2 deletion syndrome (22q11.2 DS) is the most common chromosomal microdeletion disorder. Associated problems in 22q11.2 DS may include cardiac abnormalities, immune dysfunction, facial dysmorphism, with endocrine, genitourinary and gastrointestinal problems, and developmental delay. The aim of this study was to evaluate and present all endocrinological findings of patients with 22q11.2 DS from a single center.Methods: All participants had confirmed 22q11.2 DS by fluorescence in situ hybridization with hypoparathyroidism. Data were retrieved by retrospective review of patient records.Results: A total of 17 patients were reviewed. On physical examination, all patients had similar dysmorphic features. The median age at diagnosis was 45 days (1 day-13 years). Most cases (64.7%, 11/17) were diagnosed with hypoparathyroidism incidentally after routine tests. At the time of diagnosis, mean calcium was 7.04 & PLUSMN;0.80 mg/dL, phosphorus was 6.2 & PLUSMN;1.1 mg/dL, and median parathyroid hormone (PTH) was 11.5 (3.7-47.6) ng/L. Transient hypoparathyroidism was detected in five cases (29.4%). There was no significant difference between patients with permanent or transient hypoparathyroidism regarding gender, age at diagnosis, calcium, phosphorus, and PTH levels. However, vitamin D levels were significantly lower in the transient group (p=0.036). During follow-up, short stature, obesity, and type 2 diabetes mellitus were absent. Thyroid autoantibodies were detected in two patients with normal thyroid function tests. Despite there being no pathological short stature, final stature was shorter than the general population (mean height standard deviation score:-0.94 & PLUSMN;0.83).Conclusion: Hypocalcemia may be detected during acute illness in some cases where hypocalcemia appears at later ages. There was no significant difference between permanent and transient hypoparathyroidism cases in terms of PTH level. Recognition of the more specific facial findings is important to trigger investigation of genetic variants, additional anomalies, and for follow-up.
Association between p16(cdkn2a) c540g polymorphism and tumor behavior in prolactinoma: A single-center study
(Spandidos Publ Ltd, 2014-07-01) Karkucak, Mutlu; Gül, Özen Öz; ÖZ GÜL, ÖZEN; Yakut, Tahsin; Sağ, Şebnem Özemri; ÖZEMRİ SAĞ, ŞEBNEM; Ersoy, Canan; ERSOY, CANAN; Tuncel, Ercan; Ertürk, Erdinç; ERTÜRK, ERDİNÇ; Cander, Soner; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Endokrinoloji ve Metabolizma Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Anabilim Dalı.; AAJ-6536-2021; AAH-8861-2021; AAI-1005-2021; ABI-5648-2022; AAH-8355-2021
Pituitary tumors usually originate as benign sporadic adenomas and develop into invasive and aggressive tumors such as prolactinomas, which are common functioning pituitary adenomas. The aim of the present study was to examine the association between the tumor behavior in prolactinomas and the p16(CDKN2A) gene polymorphism occurring at the 3'-untranslated region of exon 3 (C540G). A total of 104 patients with prolactinoma were included and assigned to two groups based on invasive vs. non-invasive tumor behavior. Ki67 indices were recorded according to histopathology results. Genotypic analysis of the p16( CDKN2A) C540G polymorphism was carried out using a modified polymerase chain reaction-restriction fragment length polymorphism assay. The corresponding frequencies for CC, CG and GG genotypes in non-invasive vs. invasive tumors were 61.5, 30.8, 7.7 and 64.1, 28.2, 7.7%, respectively ( not significant). The observed CG genotype frequency was higher compared with previous studies. In addition, the patients with giant adenomas or a high Ki67 index had a higher frequency of the CG genotype as compared with the other subgroups, although the differences were not significant (46.2 and 42.9%, respectively). In conclusion, a higher frequency of the C540G CG genotype of the CDKN2A gene was found among patients with prolactinoma in comparison with previous studies. These frequencies were also higher in the subgroups with elevated Ki67 or giant adenomas. Further studies are required to improve the definition of the role of the CG genotype in the development and progression of tumors in prolactinomas.
Association of the ACE I/D Gene Polymorphisms with JAK2V617F-Positive Polycythemia Vera and Essential Thrombocythemia
(Mary Ann Liebert, 2015-06-01) Görükmez, Orhan; Sağ, Şebnem Özemri; Görükmez, Özlem; Türe, Mehmet; Topak, Ali; Şahintürk, Serdar; Özkaya, Güven; Gülten, Tuna; Ali, Rıdvan; Yakut, Tahsin; ÖZEMRİ SAĞ, ŞEBNEM; Görükmez, Özlem; Türe, Mehmet; Topak, Ali; ŞAHİNTÜRK, SERDAR; ÖZKAYA, GÜVEN; Gülten, Tuna; ALİ, RIDVAN; Yakut, Tahsin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı/Hematoloji Bilim Dalı.; 0000-0002-9241-0896; 0000-0003-0297-846X; IUN-6616-2023; ACQ-9887-2022; AAH-8355-2021; A-4421-2016; HNQ-2791-2023; ECY-8582-2022; EYU-9227-2022; GXD-8209-2022; GIS-1493-2022
The renin-angiotensin system contributes to cell growth, proliferation, and differentiation in the bone marrow. We investigated the role of the ACE I/D gene polymorphism in 108 polycythemia vera (PV) and essential thrombocytosis (ET) patients who were positive for the JAK2V617F mutation, with a thrombosis group (TG) of 95 patients who had a history of vascular events, but did not have a history of myeloproliferative neoplasms and compared these to a healthy control group (CG) of 72 subjects. In the patients, II genotype and I allele frequency (p=0.009, odds ratio [OR]=9.716, 95% confidence interval [CI]=1.242-76.00, p=0.004, OR=2.019, 95% CI=1.243-3.280, respectively) were found to be higher than those in the controls. The DD genotype (p=0.021, OR=0.491, 95% CI=0.268-0.899) and D allele (p=0.004, OR=0.495, 95% CI=0.305-0.805) were found to be correlated with a decreased risk of a myeloproliferative neoplasm. These findings support the hypothesis that the ACE II genotype and I allele may be related to increased risk of ET and PV. Conversely, the DD genotype and D allele may be related to decreased risk of ET and PV. The results also indicated that the ACE I/D gene polymorphism was independent of thrombosis formation.
Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal tunnel syndrome
(Springer, 2014-12-16) Eroğlu, Pınar; İnal, Esra Erkol; Sağ, Şebnem Özemri; Görükmez, Özlem; Topak, Ali; Yakut, Tahsin; Uludağ Üniversitesi/Tıp Fakültesi//Tıbbi Genetik Anabilim Dalı.; HNQ-2791-2023; AAH-8355-2021; AFZ-0764-2022; 36638231300; 57188923466; 55313334700; 6602802424
Oxidative stress was related with carpal tunnel syndrome (CTS). We aimed to clarify the associations between glutathione S-transferase (GST)M1, GSTT1 and GSTP1-Ile105Val polymorphisms and CTS. One hundred-forty patients with CTS and 97 healthy controls were enrolled in this study. Tinel and Phalen signs were noted as positive or negative. Functional and clinical status of patients was evaluated by the Boston Questionnaire. The intensity of hand and/or wrist pain was evaluated on 10 cm visual analog scale (VAS). We applied the polymerase chain reaction (PCR) to determine the polymorphisms of the GSTM1 and GSTT1 and the PCR-restriction fragment length polymorphism method for detecting the GSTP1-Ile105Val polymorphism. The M1 null genotype was significantly higher in patients with CTS compared to healthy controls, and the M1 null genotype seemed to increase the risk of CTS approximately two-fold (P = 0.011; odds ratio (OR) = 1.98; 95 % confidence interval (CI) 1.17-3.36). The M1 null, T1 present combined genotype was significantly higher in patients with CTS compared to healthy controls (P = 0.043); however, it seemed not to increase the risk of CTS (P = 0.14; OR = 0.62; 95 % CI 0.33-1.76). We found significantly higher levels of the VAS, Boston Symptom Severity Scale and Phalen sign in patients with the Ile/Val or the Val/Val genotypes compared to those in patients with the Ile/Ile genotype (P = 0.003, 0.004 and 0.044, respectively). We proposed that genes involved in the protection from oxidative stress may influence the susceptibility, clinical and functional status of CTS. The GSTM1 null genotype may be related with the development of CTS, whereas the Val allele of GSTP1-Ile105Val polymorphism may be associated with worse functional and clinical status in CTS.
Characterization and in silico analyses of the BRCA1/2 variants identified in individuals with personal and/or family history of BRCA-related cancers
(Elsevier, 2020-11-01) Pirim, Dilek; Kaya, Niyazi; Yıldırım, Elif Uz; Sağ, Şebnem Özemri; Temel, Şehime Gülsün; Bursa Uludağ Üniversitesi/Fen Edebiyat Fakültesi/Moleküler Biyoloji ve Genetik Bölümü.; Bursa Uludağ Üniversitesi/Fen Bilimleri Enstitüsü/Moleküler Biyoloji ve Genetik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 0000-0002-0522-9432; 0000-0002-9802-0880; ABA-4957-2020; FEL-0562-2022; AAB-4296-2021; AAH-8355-2021; AAG-8385-2021; 55978575700; 57217533949; 13807893000; 36638231300; 6507885442
Pathogenic variants in the coding regions of the BRCA1/2 lead dysfunctional or nonfunctional BRCA proteins however the contribution of non-coding BRCA1/2 variants to BRCA-related disease risk has not been fully elucidated. Thus, we characterized the functional impact of both coding and non-coding BRCA1/2 variants identified in individuals with personal and/or family history of BRCA-related cancers. The data were produced by resequencing the exons and exon-intron junctions of the BRCA1/2 in 125 individuals and were comprehensively analyzed by using bioinformatics tools and databases. A total of 96 variants (59 coding and 37 non-coding) including 7 novel variants were identified and analyzed for their functional importance. We identified 11 missense variants that potentially affect protein function; 22 variants were likely to alter different types of posttranslational modifications. Also, multiple non-coding BRCA1/2 variants were found to reside in the critical regulatory regions that have the potential to act as eQTLs and affect alternative splicing. The results of our study shed light on the possible contributions of not only coding variants but also non-coding BRCA1/2 variants in BRCRA-related cancers. Further investigation is required to fully understand their potential associations with phenotypes which may ultimately lead their utilization on cancer management as a biomarker.
Consistency of variant interpretations among bioinformaticians and clinical geneticists in hereditary cancer panels
(Springernature, 2022-02-08) Ağaoğlu, Nihat Buğra; Ünal, Büşra; Doğan, Özlem Akgun; Kanev, Martin Orlinov; Zolfagharian, Payam; Sağ, Şebnem Özemri; Temel, Şehime Gülsün; Doganay, Levent; ÖZEMRİ SAĞ, ŞEBNEM; 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 Bölümü.; AAH-8355-2021; AAG-8385-2021
Next-generation sequencing (NGS) is used increasingly in hereditary cancer patients' (HCP) management. While enabling evaluation of multiple genes simultaneously, the technology brings to light the dilemma of variant interpretation. Here, we aimed to reveal the underlying reasons for the discrepancy in the evidence titles used during variant classification according to ACMG guidelines by two different bioinformatic specialists (BIs) and two different clinical geneticists (CGs). We evaluated final reports of 1920 cancer patients and 189 different variants from 285 HCP were enrolled to the study. A total of 173 of these variants were classified as pathogenic (n = 132) and likely pathogenic (n = 41) by the BI and an additional 16 variants, that were classified as VUS by at least one interpreter and their classification would change the clinical management, were compared for their evidence titles between different specialists. The attributed evidence titles and the final classification of the variants among BIs and CGs were compared. The discrepancy between P/LP final reports was 22.5%. The discordance between CGs was 30% whereas the discordance between two BIs was almost 75%. The use of PVS1, PS3, PP3, PP5, PM1, PM2, BP1, BP4 criteria markedly varied from one expert to another. This difference was particularly noticeable in PP3, PP5, and PM1 evidence and mostly in the variants affecting splice sites like BRCA1(NM_007294.4) c.4096 + 1 G > A and CHEK2(NM_007194.4) c.592 + 3 A > T. With recent advancements in precision medicine, the importance of variant interpretations is emerging. Our study shows that variant interpretation is subjective process that is in need of concrete definitions for accurate and standard interpretation.
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.
Diagnostic efficiency of clinical exome solution panel in patients with hearing loss/hereditary deafness by using next generation sequencing
(Springernature, 2020-12-01) ; Sağ, Şebnem Özemri; ÖZEMRİ SAĞ, ŞEBNEM; Alemdar, A.; ALEMDAR, ADEM; Yılmaz, M.; Aliyeva, L.; ALIYEVA, LAMIYA; Temel Şehime Gülsün; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Top Anabilim Dalı.; 0000-0002-9802-0880; HIZ-7332-2022; AAH-8355-2021; AAG-8385-2021
Dyskeratosis congenita: A case report
(Medecine et Hygiene, 2016) Görükmez, Özlem; Carrillo, Jaime; Perona, R.; Sağ, Şebnem Özemri; Topak, Ali; Türe, Mehmet; Şahintürk, Serdar; Gülten, Tuna; Yakut, Tahsin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; 0000-0002-7612-0055; AAH-8355-2021; HOQ-5853-2023; ECY-8582-2022; ACQ-9887-2022; EYU-9227-2022; GIS-1493-2022; 57193738647; 55313334700; 6602186133; 57214054591; 6505944216; 6602802424
Glutathione S-transferase M1 and T1 gene polymorphisms in patients with chronic plaque-type psoriasis: A case-control study
(Karger, 2015-11-03) Solak, Berna; Karkucak, Mutlu; Turan, Hakan; Uslu, Esma; Erdem, Teoman; Ocakoğlu, Gökhan; Sağ, Şebnem Özemri; Yakut, Tahsin; Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; AAH-8355-2021; AAH-5180-2021; 57073882900; 57116515700; 6602802424
Objective: To determine the role of glutathione S-transferase (GST) isoenzyme polymorphisms as susceptibility factors in patients with psoriasis in a Turkish cohort. Subjects and Methods: In this case-control study, 105 patients with plaque-type psoriasis and 102 healthy controls were recruited from the dermatology outpatient clinics of two university hospitals. Genomic DNA was extracted from whole blood using a DZ DNA isolation kit. Multiplex PCR was used to determine GSTM1 and GSTT1 polymorphisms in the isolated DNAs. Results: Of the 150 patients with psoriasis, 83 (79%) were identified with the GSTT1 genotype and 22 (21%) with the null genotype. Of the 102 patients in the control group, 69 (67.6%) subjects were identified with the GSTT1 genotype and 33 (32.4%) with the null genotype. There was no significant difference between the patient and control groups (p = 0.063). Regarding the GSTM1 polymorphism, 54 (51.4%) patients were identified with this genotype and 51 (48.6%) with the null genotype; in the control group, 50 (49%) were identified with this genotype and 52 (51%) with the null genotype. Again there was no statistically significant difference between the groups (p = 0.957). Conclusion: In this Turkish cohort of patients with psoriasis, neither GSTT1 nor GSTM1 polymorphisms were associated with disease susceptibility. Larger studies with a wider range of GST isoenzyme are needed.
GST (GSTM1, GSTT1, and GSTP1) polymorphisms in the genetic susceptibility of Turkish patients to cervical cancer
(Korean Soc Gynecology Oncology & Colposcopy, 2010-09) Kıran, Beray; Karkucak, Mutlu; Ozan, Hakan; Yakut, Tahsin; Özerkan, Kemal; Sağ, Şebnem Özemri; Türe, Mehmet; Uludağ Üniversitesi/Tıp Fakültesi/Kadın Hastalıkları ve Doğum Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; AAH-9791-2021; 36637703500; 35388323500; 7003908072; 6602802424; 6603345841; 36638231300; 6602186133
Objective: This work investigates the role of glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and glutathione S-transferase P1 (GSTP1) enzymes and polymorphisms, which are found in phase II detoxification reactions in the development of cervical cancer. Methods: This study was conducted with 46 patients diagnosed with cervical cancer and 52 people with no cancer history. Multiplex PCR methods were used to evaluate the GSTM1 and GSTT1 gene polymorphism. However, the GSTP1 (Ile105Val) gene polymorphism was studied using a PCR-RFLP method. The patient and control groups were compared using a chi-square test with p<0.05. Results: In the patient group, statistical significance was determined for gravidity (p=0.03), parity (p=0.01), and the number of living children (p=0.01) compared to the control group. The gene frequency of GSTM1, GSTT1, and GSTP1 polymorphisms was evaluated. We observed that GSTM1 and GSTT1 null genotype frequencies were 54.3% and 32.6% respectively, while GSTP1 (Ile/Val), (Ile/Ile), (Val/Val) genotype frequencies were 52%, 44%, and 4%, respectively, in the cervical cancer patients. No statistical variation was determined between the control and patient groups in terms of GSTM1, GSTT1, and GSTP1 polymorphisms (p>0.05). Conclusion: Our results demonstrate that GSTT1, GSTM1, and GSTP1 polymorphisms are not associated with cervical cancer in Turkish patients.
Investigation of FGFR4 (Gly388Arg) gene Polymorphism in primary lung cancer Patients
(Kamla-Raj Enterprises, 2015-03-01) Türe, Mehmet; Yakut, Tahsin; Deligönül, Adem; Karkucak, Mutlu; Sağ, Şebnem Özemri; Hartavi, Mustafa; Çubukcu, Erdem; Gülten, Tuna; Evrensel, Türkkan; Türe, Mehmet; Yakut, Tahsin; DELİGÖNÜL, ADEM; ÖZEMRİ SAĞ, ŞEBNEM; Hartavi, Mustafa; ÇUBUKÇU, ERDEM; Gülten, Tuna; EVRENSEL, TÜRKKAN; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Onkoloji Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/İç Hastalıkları Anabilim Dalı.; 0000-0002-9732-5340; AAJ-1027-2021; AAH-8355-2021; ECY-8582-2022; GIS-1493-2022; ESM-4544-2022; CUI-5353-2022; ETP-1691-2022; EYU-9227-2022
Several studies have shown relationships between predisposition to various types of cancer and polymorphisms of the fibroblast growth factor receptor 4 (FGFR4) gene. In the present study, researchers investigated the relationship between primary lung cancer and (PLC) FGFR4 Gly388Arg polymorphism in regard to tendency, histopathologic sub-type, early onset, and metastatic status. The present study included 124 PLC patients and 100 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify gene polymorphism of FGFR4 Gly388Arg. Statistical significance was considered when p < 0.05, and a statistically significant difference was not found in FGFR-4 polymorphism between the patient group and control group in regard to tendency, histopathologic sub-type, early onset, and metastatic status (p > 0.05). The findings in this study demonstrated that there was no relationship between polymorphism of FGFR4 Gly388Arg gene and PLC. However, these results should be confirmed in larger studies and in specific histopathological sub-types of PLC.
Kronik Miyelositer Lösemilerde füzyon gen kalitatif ve kantitatif değerlerinin FISH ve moleküler genetik yöntemlerle karşılaştırılması
(Uludağ Üniversitesi, 2010) Sağ, Şebnem Özemri; Yakut, Tahsin; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.
BCR-ABL pozitif hücrelerin tespitinde, Floresan In Situ Hibridizasyon (FISH) ve Kantitatif Revers Transkriptaz Polimeraz Zincir Reaksiyonunu (QRT-PCR) içeren moleküler tanısal yöntemler, klasik sitogenetik analize göre daha sensitiftir. QRT-PCR, üstün sensitivitesinden dolayı, İmatinib ile tedavi edilen Kronik Miyelositer Lösemilerin (KML) takibinde altın standart olarak düşünülmektedir. Bizim çalışmamızın amacı, KML hastalarında farklı zamanlarda FISH ve QRT-PCR'ın diagnostik ve klinik faydalılığının karşılaştırılmasıdır.Gereç ve Yöntem: Bu çalışmada, retrospektif olarak analiz edilen 78 KML hastasının 135 sonucu Philadelphia (Ph) translokasyonu için hem FISH hem de QRT-PCR çalışmaları ile test ettik ve bu iki farklı tekniğin avantaj ve dezavantajlarını değerlendirdik.Bulgular: Bizim çalışmamız, yeni tanı konmuş vakaların tümünün her iki metotla pozitif olduğunu gösterdi. Bir vakada, FISH pozitifti, QRT-PCR negatifti; 61 vakada QRT-PCR pozitifken FISH negatifti. FISH ve QRT-PCR'ın tam uyumu (her iki testte negatif veya pozitif olma) 73 vakada bulundu (%54,1) ve 62 vakada (%45,9) farklılık tanımlandı. Aynı zamanda QRT-PCR değerleri ile sitogenetik yanıt kategorileri arasında iyi bir uyum vardı.Sonuç: QRT-PCR'ın düşük seviyelerdeki BCR-ABL transkriptlerini tam olarak ölçmeye izin verdiğini ve minimal rezidüel hastalığın (MRH) hassas br göstergesi olarak hizmet verdiğini doğruladık. Ek olarak, yeni tanı konmuş KML hastaları arasında BCR-ABL füzyon genini tespit etmede FISH ile QRT-PCR `ın %100 korele olduğunu gösterdik. Aynı zamanda FISH'in minimal rezidüel hastalığın takibinde uygun olmadığı sonucuna vardık.
Low ratio mosaic marker chromosomes in prenatal diagnosis
(Springer, 2007) Yakut, Tahsin; Gülten, Tuna; Sağ, Şebnem Özemri; Evke, Elif; Cangül, Hakan; Temel, Sehime; Karkucak, Mutlu; Uludağ Üniversitesi/Tıp Fakültesi.; AAH-8355-2021; ABI-5648-2022; AAG-8385-2021
Mefv gen mutasyonları taşıyan bireylerde yeni nesil dizileme yöntemi ile elde edilmiş yaygın ve yeni varyantların veri tabanlarında analizleri: retrospektif çalışma
(Bursa Uludağ Üniversitesi, 2019) Kurt, Zeynep; Yıldırım, Elif Uz; Sağ, Şebnem Özemri; Bursa Uludağ Üniversitesi/Fen Bilimleri Enstitüsü/Moleküler Biyoloji ve Genetik Anabilim Dalı.; 0000-0003-2466-2335; 0000-0002-1459-5485; 0000-0002-3948-8889
MEFV geni 16. Kromozomun kısa kolu üzerinde 115 kb’lık bir bölge üzerindedir. Bu gen yaklaşık 3.7 kb uzunluğunda bir transkript kodlar. Genin ürünü 781 aminoasitlik pirin proteinidir. Pirin sadece olgun granülositlerde ifade olur. Pirinin görevi nötrofil aktivasyonunu azaltıp inflamasyonu baskılamaktır. Pirinin dört domaininden biri olanB30.2’dur. B30.2 bölgesinin ekspresyonu ile kaspaz-1 aktivasyonu olur ve IL-1b üretimini azaltır. Pirin mutasyona uğrayınca sıradan uyarıcılara cevap olarak aşırı derecede IL-1b üretimine neden olur. Çalışmalar atak döneminde İnterlökin IL–2, IL–6, IL–8 veTümör Nekroz Faktör-alfa (TNF-α) düzeylerinin yüksek olduğu saptanmıştır.FMF (familial mediterranean fever) hastalığı MEFV genindeki mutasyonlar sonucu ortaya çıkan otoinflamatuar hastalıkların en sık görülenidir. Hastalık ani başlayan ateş ve seröz zarların inflamasyonu ile karakterizedir. Akdeniz çevresinde yaygın olan hastalık Seferadik Yahudier, Ermeniler, Araplar ve Türkler arasında yaygındır. Bu çalışmanın amacı FMF hastalığına sebep olan MEFV geni varyantlarını tespit etmek, sınıflandırmak ve yeni varyantlar tespit edip varyant sınıflandırmasına kazandırmaktır. Çalışmaya katılan 673 erkek, 841 kadın toplam 1514 hastadan alınan kan örnekleriyle NGS dizilime yardımıyla gen analizi yapılmıştır. Sophia DDM progamıyla analizisonucun da 75 tanesi ekzonda 29 tanesi intronda olmak üzere 104 varyant tespit edilmiştir. Tespit edilen bu varyantların 7 tanesi ekzonik 6 taneside intronik olmak üzere 13 tanesi novel varyanttır. Sonra elde edilen bu varyantlar çeşitli insilico analizler kullanarak patojenik özellikte olup olmadığına göre çeşitli sınıflandırmalara tabi tutulmuştur. Ayrıca birçok veritabanıyla analiz edilerek posttranslasyonel modifikasyonlarda rolü olup olmadığı anlaşılmaya çalışılmıştır. Elde edilen varyantların allel frekansı üzerine çalışılarak ne kadar sıklıkla görüldüğü hakkında bilgi edinilmeye çalışılmıştır.
Multiple congenital anomalies in a child with 47,XY,+der(8;9)(p10;p10): A case report
(Medecine Et Hygiene, 2015-01-01) Görükmez, O.; Görükmez, Orhan; Sağ, Şebnem Özemri; Yakut, T.; Gülten, Tuna; Görükmez, Orhan; ÖZEMRİ SAĞ, ŞEBNEM; Yakut, T.; Gülten, Tuna; Uludağ Üniversitesi/Tıp Fakültesi/Genetik Bölümü; 0000-0002-9241-0896; 0000-0002-9241-0896; AAH-8355-2021; AFZ-0764-2022; GIS-1493-2022; EYU-9227-2022
Multiple congenital anomalies in a child with 47,XY,+der(8;9)(p10;p10): a case report: Complex small supernumerary marker chromosomes (sSMC) constitute one of the smallest subgroups of sSMC in general. Complex sSMC consist of chromosomal material derived from more than one chromosome. We report a complex sSMC derived from chromosomes 9 and 8, characterized as der(8;9)(p10;p10) resulting from unbalanced transition of maternal balanced translocation. Besides dysmorphic face and mental-motor retardation, the patient had Dandy-Walker malformation (DWM) in cranial MR also. As far as we are concerned, this is the first complex sSMC case comprising short arms of 8th and 9th chromosomes.
Novel homozygous missense mutation in NARS1 gene: A new neurodevelopmental disorder with microcephaly
(Springernature, 2022-04-01) Temel, Sehime Gülsün; Sağ, Şebnem Özemri; Eren, Erdal; Deniz, Engin; TEMEL, ŞEHİME GÜLSÜN; ÖZEMRİ SAĞ, ŞEBNEM; EREN, ERDAL; Bursa Uludağ Üniversitesi/Tıp Fakültesi.; 0000-0002-9802-0880; 0000-0002-1684-1053; JPK-3909-2023; AAG-8385-2021; AAH-8355-2021