Browsing by Author "Temel, Şehime G."

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Identification of a novel de novo COMP gene variant as a likely cause of Pseudoachondroplasia
(Lippincott Williams & Wilkins, 2021-08-01) Tuncel, Gülten; Akcan, Neşe; Gül, Şeref; Sağ, Şebnem Ö.; Bundak, Ruveyde; Mocan, Gamze; Temel, Şehime G.; Ergoren, Mahmut C.; 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.; 0000-0002-9802-0880; AAH-8355-2021; AAG-8385-2021
Next-generation sequencing technology and advanced sequence analysis techniques are markedly speeding up the identification of gene variants causing rare genetic diseases. Pseudoachondroplasia (PSACH, MIM 177170) is a rare disease inherited in an autosomal dominant manner. It is known that variations in the cartilage oligomeric matrix protein (COMP) gene are associated with the disease. Here, we report a 39-month-old boy with short stature. He gave visible growth and development delayed phenotype after 12 months. Further genetic resequencing analysis was carried out to identified the disease-causing variant. Furthermore, computational approaches were used to characterize the effect of the variant. In this study, we identify and report a novel variation in the COMP gene, c.1420_1422del (p.Asn47del), causing a spontaneous form of PSACH in our patient. Our in silico model indicated that any mutational changes in this region are very susceptible to PASCH phenotype. Overall, this study is the first PSACH case in the Turkish Cypriot population. Moreover, this finding contributes to the concept that the genotype-phenotype correlation in COMP is still unknown and also improves our understanding of this complex disorder.
Increased radiosensitivity and impaired DNA repair in patients with STAT3-LOF and ZNF341 deficiency, potentially contributing to malignant transformations
(Oxford Univ Press, 2022-05-02) Çekiç, Şükrü; Hüriyet, Hüzeyfe; Hortoğlu, Melika; Kasap, Nurhan; Özen, Ahmet; Karakoç-Aydıner, Elif; Metin, Ayşe; Ocakoğlu, Gökhan; Demiröz Abakay, Candan; Temel, Şehime G.; Özemri Sağ, Şebnem; Barış, Safa; Çavaş, Tolga; Şebnem Kılıç, Sara; ÇEKİÇ, ŞÜKRÜ; Hüriyet, Hüzeyfe; BEKTAŞ HORTOĞLU, MELİKA; OCAKOĞLU, GÖKHAN; DEMİRÖZ ABAKAY, CANDAN; TEMEL, ŞEHİME GÜLSÜN; ÖZEMRİ SAĞ, ŞEBNEM; ÇAVAŞ, TOLGA; KILIÇ GÜLTEKİN, SARA ŞEBNEM; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Pediatrik İmmünoloji Anabilim Dalı.; Bursa Uludağ Üniversitesi/Fen-Edebiyat Fakültesi/Biyoloji Bölümü/Hücre Kültürü ve Genetik Toksikoloji Laboratuvarı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Biyoistatistik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Radyasyon Onkolojisi Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Translasyonel Tıp Anabilim Dalı.; 0000-0002-9574-1842 ; 0000-0002-5617-8313 ; 0000-0001-5380-5898 ; 0000-0003-1620-1918 ; L-1933-2017; CVI-9578-2022; JBJ-7521-2023; HLG-6346-2023; AAH-3855-2021; AAG-8385-2021; AAH-8355-2021; AAH-3508-2021; IMT-6140-2023
STAT3 plays an important role in various complex and sometimes contradictory pathways such as proliferation, differentiation, migration, inflammation, and apoptosis. The transcriptional activity of the STAT3 gene is controlled by a transcription factor called ZNF341. There is insufficient data on radiation sensitivity and post-radiation DNA repair in STAT3- loss-of-function (LOF) patients. We aimed to investigate the radiosensitivity in patients with STAT3-LOF and ZNF341 deficiency. Twelve patients with STAT3-LOF and four ZNF341-deficiency patients were recruited from three clinical immunology centers in Turkey and evaluated for radiosensitivity by the Comet assay, comparing to 14 age- and sex-matched healthy controls. The tail length (TL) (mu m), percentage of DNA in the tail (TDNA%), and olive tail moment (OTM) (arbitrary units) were evaluated at the same time for baseline (spontaneous), initial (immediately after 2 Gy irradiation), and recovery (2 h after irradiation) periods by using a computerized image-analysis system, estimating DNA damage. Except for a patient with ZNF341 deficiency who developed nasal cell primitive neuroendocrine tumor and papillary thyroid cancer during the follow-up, there was no cancer in both groups. During the recovery period of irradiation, TL, TDNA%, and OTM values of healthy controls decreased rapidly toward the baseline, while these values of patients with STAT3-LOF and ZNF341 deficiency continued to increase, implying impaired DNA repair mechanisms. Increased radiosensitivity and impaired DNA repair were demonstrated in patients diagnosed with STAT3-LOF and ZNF341 deficiency, potentially explaining the susceptibility to malignant transformation.This study demonstrates for the first time that patients with STAT3-LOF and ZNF341 deficiency had increased radiation sensitivity and DNA repair defects compared with healthy controls. Our results highlight the need for close monitoring of these patients for the development of malignancy.
Lysinuric protein intolerance and HOIP deficiency in a boy: SLCA7A and RNF31 gene disruptions
(Elsevier, 2018-08-30) Görükmez, Orhan; Türkgenç, Burcu; Gürkan, Hakan; Aliyeva, Lamiya; Erdöl, Şahin; Yaralı, Yasin; Baytan, Birol; Sağlam, Halil; Kılıç, Şebnem; Temel, Şehime G.; Uludağ Üniversitesi/Tıp Fakültesi Anabilim Dalı/Tıbbi Genetik Bölümü.; 0000-0003-0710-5422; AAG-8385-2021; C-7392-2019; AAH-1658-2021
Mikrodalga ışınımının sıçan karaciğer ve böbrek dokularının preparasyonunda kullanımı
(Uludağ Üniversitesi, 2002-11-01) Temel, Şehime G.; Noyan, Semiha; Uludağ Üniversitesi/Sağlık Bilimleri Enstitüsü/Histoloji ve Embriyoloji Anabilim Dalı.
Histopatoloji laboratuvarlarında parafin kesit preparasyonunda ilk basamak olan fiksasyon ve bunu izleyen doku takibi, gömme ve boyama aşamalarının süresi; kullanılan tekniğe göre değişmektedir. Herhangi bir yardımcı teknik kullanılmadan bu işlemler oda sıcaklığında gerçekleştirildiği takdirde; 1-4 günde dokular ancak gömme safhasına getirilebilmektedir. Sıcaklığın kimyasal reaksiyonları arttırıcı etkisinden yararlanmak düşüncesiyle histopatoloji laboratuvarlarında preparasyonun değişik aşamalarında; düdüklü tencere, etüv ve son yıllarda mikrodalga fırınlar kullanılmaktadır. Bu çalışmada; fiksasyondan boyamaya kadar tüm aşamaların mikrodalga fırında yapılması amaçlandı. Bu amaçla sıçanlardan alınan karaciğer parçalan nötral formalinde, böbrek parçalan ise % 10 formalinde mikrodalga ışınımı ile fikse edildi. Sonrasında gelen doku takibi aşamalan da mikrodalga fırında gerçekleştirildi. Ancak rutin işlemlerden farklı olarak, saydamlaştıncı ajan ksilol yerine yanıcı özelliği olmadığı için mikrodalga fırında güvenle kullanılabilen 1,1,1 trikloroetan kullanıldı. Parafine gömülen dokulardan alman kesitlere mikrodalga ışınımı yardımı ile hematoksilen ve eozin boyaması uygulandı. Elde edilen preparatlar, oda sıcaklığında yapılan konvansiyonel (ksilol kullanılan) ve 1,1,1 trikloroetan grubu ile karşılaştırıldığında yapısal korunma ve boyanma kalitesi açısından istatistiksel olarak anlamlı bir fark olmadığı saptandı. Mikrodalga fırında gerçekleştirilen işlemlerin tümü yaklaşık olarak 2 saat 10 dakikada tamamlandı. Rutin patoloji laboratuvarlarında uygulanan parafin blok işlemlerinin yaklaşık olarak 24 saatte tamamlandığı göz önünde tutulursa; tanısal kriterler ve tedavi süreci açısından önemli olabilecek durumlarda, anlamlı bir zaman kazancı sağladığı için; mikrodalga-yardımlı preparasyon tekniğinin alternatif olarak kullanılabileceği düşünüldü.
Mutations in PIEZO2 cause gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5
(Cell Press, 2014-04-20) McMillin, Margaret J.; Beck, Anita E.; Chong, Jessica X.; Shively, Kathryn M.; Buckingham, Kati J.; Gildersleeve, Heidi I. S.; Aracena, Mariana I.; Aylsworth, Arthur S.; Bitoun, Pierre; Carey, John C.; Clericuzio, Carol L.; Crow, Yanick J.; Curry, Cynthia J.; Devriendt, Koenraad; Everman, David B.; Fryer, Alan; Gibson, Kate; Uzielli, Maria Luisa Giovannucci; Graham, John M., Jr.; Hall, Judith G.; Hecht, Jacqueline T.; Heidenreich, Randall A.; Hurst, Jane A.; Irani, Sarosh; Krapels, Ingrid P. C.; Leroy, Jules G.; Mowat, David; Plant, Gordon T.; Robertson, Stephen P.; Schorry, Elizabeth K.; Scott, Richard H.; Seaver, Laurie H.; Sherr, Elliott; Splitt, Miranda; Stewart, Helen; Stumpel, Constance; Temel, Şehime G.; Weaver, David D.; Whiteford, Margo; Williams, Marc S.; Tabor, Holly K.; Smith, Joshua D.; Shendure, Jay; Nickerson, Deborah A.; Washington, Univ; Bamshad, Michael J.; TEMEL, ŞEHİME GÜLSÜN; Uludağ Üniversitesi/Tıp Fakültesi/Tıbbi Genetik Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Embriyoloji Anabilim Dalı.; AAG-8385-2021
Gordon syndrome (GS), or distal arthrogyposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechano-sensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value < 0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.
A new material for prevention of epidural fibrosis after laminectomy - Oxidized regenerated cellulose (Interceed), an absorbable barrier
(Lippincott Williams & Wilkins, 2006) Temel, Şehime G.; Öztürk, Çağatay; Temiz, Aytun; Ersözlü, Salim; Aydınlı, Ufuk; Uludağ Üniversitesi/Tıp Fakültesi/Ortopedik Cerrahi Anabilim Dalı.; Uludağ Üniversitesi/Tıp Fakültesi/Histoloji ve Tıbbi Genetik Anabilim Dalı.; 0000-0003-3133-206X; S-6686-2019; AAG-8385-2021
Epidural fibrosis, which may cause persistent back and leg pain, may develop after laminectomy. Several materials have been used in attempts to minimize epidural fibrosis, with varying results. We evaluated the efficacy of an absorbable cellulose adhesion barrier in preventing epidural fibrosis. In 25 New Zealand white rabbits, laminectomies were performed at L3 and L5 vertebrae. The dura mater was covered by the adhesion barrier (Interceed, TC7, Johnson & Johnson, USA) at L3 laminectomy site (group 1), with L5 laminectomy site serving as an internal control (group 2) in each animal. There was no neurological deficit in any of the animals during the postoperative period. Animals were sacrificed at postoperative day 28. The lumbar spine was removed en bloc and placed in neutral, buffered formalin for 72 h. The specimens were then decalcified and embedded in paraffin. Permanent sections of 5 to 7 mu m were stained with hematoxylin and eosin and Masson trichrome dye. Epidural fibrosis was evaluated in a double-blinded manner. The extent of epidural fibrosis was graded as 0, no reaction seen; 1, mild reaction; 2, moderate reaction; 3, extensive reaction, and 4, severe reaction. The histological findings of each group were compared. For the statistical analysis, Wilcoxon signed rank test was used. In group 1, the fibrotic tissue formation was minimal in 19 and moderate in 6 laminectomy sites. In group 2, the fibrotic tissue formation was determined as being extensive in 17 and moderate in 8 laminectomy sites. Statistical analysis showed significant decrease in epidural fibrosis in group 1 (P < 0.05). This study showed that Interceed, which is commercially available in the market, especially for abdominal and gynecological surgeries, could be used to prevent epidural fibrosis.
Strong association between serotonin transporter 5- htt vntr variant and psychoactive substance (nicotine) use in the Turkish cypriot population
(Bentham Science Publ Ltd, 2020-01-01) Kandemis, Emine; Tuncel, Gülten; Asut, Özen; Ergoren, Mahmut C.; Temel, Şehime G.; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Anabilim Dalı.; 0000-0002-9802-0880; AAG-8385-2021
Background: The use of psychoactive substances is one of the most dangerous social problems worldwide. Nicotine dependence results from the interaction between neurobiological, environmental and genetic factors. Semtonin is a neurotransmitter that has a wide range of central nervous system activities. The serotonin transporter gene has been previously linked to psychological traits.Objective: A variable number of tandem repeats within the serotonin transporter-linked polymorphic gene region are believed to alter the transcriptional efficiency of the 5-HTT gene. Therefore, we aimed to investigate the association between this polymorphic site and smoking behavior in the Turkish Cypriot population.Methods: A total of 259 (100 smokers, 100 non-smokers and 59 ex-smokers) Turkish Cypriots were included in this population-based cross-sectional study. Genomic DNA was extracted from peripheral blood samples and the 5-HTTVNTR2 polymorphisms were determined by the PCR-RFLP.Results: The allelic frequency and genotype distribution results of this study showed a strong association (P<0.0001) between smokers and non-smokers. No statistical significance was found between non-smokers and ex-smokers.Conclusion: This is the first genetic epidemiology study to investigate the allelic frequencies of 5-HTTVNTR2 polymorphisms associated with smoking behavior in the Turkish Cypriot population. Based on the results of this study, genome-wide association studies should be designed for preventive medicine in this population.
The story of a ship journey, malaria, and the HBB gene ivs-ii-745 mutation: Circassian immigration to cyprus
(Thieme Medical Publication, 2021-03-16) Ergören, Mahmut C.; Temel, Şehime G.; Mocan, Gamze; Dündar, Munis; Temel, Şehime G.; TEMEL, ŞEHİME GÜLSÜN; Bursa Uludağ Üniversitesi/Tıp Fakültesi/Genetik Mühendisliği Anabilim Dalı.; 0000-0001-9593-9325; 0000-0002-9802-0880; 0000-0003-0969-4611; B-3150-2011; D-8491-2018; GQP-2509-2022; AAZ-6885-2021
Background During 19th century, the Circassians were secluded from their lands and forced to migrate to Ottoman Empire properties. Approximately 2,346 Circassians were exiled from Istanbul to Cyprus Island. During the deportation journey, many of Circassian were passed away in consequence of malaria and unknown reasons. Overall, 1,351 survivor Circassians managed to reach the island, however, many of them had faced with endemic malaria again in Cyprus. An autosomal recessive hematological disorder thalassemia was the second endemic health condition after malaria, whereas thalassemia carriers show resistance to malaria infections.Materials and Methods A large Cypriot family with 57 members whose grandparents were supposed to be in that ship journey has been investigated in this study. Polymerase chain reaction (PCR)-amplification refractory mutation system (ARMS) analysis technique was used for genotyping the HHB gene.Results The human beta -globin ( HBB ) gene c.316-106C>G (IVS-II-745) (II-745) heterozygous variation have been detected.Conclusion Overall, this study is a very good example for a typical natural selection. In this case, one single gene point mutation did not limit survival in the society; natively, it increased their survival changes to form new colonization and the inheritance of the mutation to the next generations.