Yazar "Koruyucu, Mine" seçeneğine göre listele
Listeleniyor 1 - 17 / 17
Sayfa Başına Sonuç
Sıralama seçenekleri
Öğe AMELX mutations and genotype-phenotype correlation in x-linked amelogenesis imperfecta(2024) Wang, Shih-Kai; Zhang, Hong; Lin, Hua-Chieh; Wang, Yin-Lin; Lin, Shu-Chun; Seymen, Figen; Koruyucu, Mine; Simmer, James P.; Hu, Jan C.-C.AMELX mutations cause X-linked amelogenesis imperfecta (AI), known as AI types IE, IIB, and IIC in Witkop's classification, characterized by hypoplastic (reduced thickness) and/or hypomaturation (reduced hardness) enamel defects. In this study, we conducted whole exome analyses to unravel the disease-causing mutations for six AI families. Splicing assays, immunoblotting, and quantitative RT-PCR were conducted to investigate the molecular and cellular effects of the mutations. Four AMELX pathogenic variants (NM_182680.1:c.2T>C; c.29T>C; c.77del; c.145-1G>A) and a whole gene deletion (NG_012494.2:g.307534_403773del) were identified. The affected individuals exhibited enamel malformations, ranging from thin, poorly mineralized enamel with a "snow-capped" appearance to severe hypoplastic defects with minimal enamel. The c.145-1G>A mutation caused a -1 frameshift (NP_001133.1:p.Val35Cysfs*5). Overexpression of c.2T>C and c.29T>C AMELX demonstrated that mutant amelogenin proteins failed to be secreted, causing elevated endoplasmic reticulum stress and potential cell apoptosis. This study reveals a genotype-phenotype relationship for AMELX-associated AI: While amorphic mutations, including large deletions and 5' truncations, of AMELX cause hypoplastic-hypomaturation enamel with snow-capped teeth (AI types IIB and IIC) due to a complete loss of gene function, neomorphic variants, including signal peptide defects and 3' truncations, lead to severe hypoplastic/aplastic enamel (AI type IE) probably caused by "toxic" cellular effects of the mutant proteins.Öğe Analyzing effects on anterior open bite in twins by PLS-SEM and sobel test(2024) Birant, Sinem; Veznikli, Mert; Kasımoğlu, Yelda; Koruyucu, Mine; Evren, Atıf Ahmet; Seymen, FigenObjective: This study aimed to assess the different pathways between predictor factors such as zygosity, atypical swallowing, mouth breathing, breastfeeding and bottle feeding related to anterior open bite (AOB) in twins. Methods: The study was conducted in monozygotic (MZ) and dizygotic (DZ) twin children aged 3-15 years. AOB, atypical swallowing, mouth breathing, feeding type, duration of bottle use, and mouth opening status during sleep were recorded during oral examination. Partial least squares structural equation model (PLS-SEM) and sobel tests were performed to assess the total and indirect effects among the variables on AOB. Results: A total of 404 children (29.2% MZ;70.8% DZ) participated in this study. The effect of zygosity on mouth breathing in the PLS-SEM model was statistically significant. Conversely, it was determined that mouth breathing effected that atypical swallowing (p = 0.001). Atypical swallowing triggered AOB (p = 0.001). The atypical swallowing has a mediation effect between AOB and mouth breathing (p = 0.020). Mouth breathing causes atypical swallowing and therefore indirectly increases the likelihood of AOB. While breastfeeding decreases AOB incidence (p = 0.023), bottle feeding increases AOB incidence (p = 0.046). The sobel tests show that the fully mediator variable feature of mouth breathing is statistically significant in the negative relation between zygosity and atypical swallowing. Conclusion: The PLS-SEM model showed that mouth breathing triggers atypical swallowing and atypical swallowing triggers AOB. As a result of this chain of relationships, an indirect effect of zygosity on AOB was observed. According to sobel tests, zygosity has an indirect effect on atypical swallowing through mouth breathing, while mouth breathing has a positive indirect effect on AOB through atypical swallowing. Clinical relevance: This study identified the relationships between different factors and the presence of AOB. The findings of this study demonstrate in detail the relationships between AOB and zygosity, atypical swallowing, mouth breathing, breastfeeding and bottle feeding. Brestfeeding has a reducing effect on the frequency of AOB. Among the nutritional forms, breastfeeding ensures the proper development of the stomatognathic system by working the oro-facial muscles.Öğe Awareness of the protective measures against Covid-19 among Turkish dentists: a questionnaire survey(2023) Kasımoğlu, Yelda; İlisulu, Sabiha Ceren; Baysan, Caner; Koruyucu, Mine; Seymen, FigenObjective: The COVID-19 pandemic has deeply affected the entire world. This study aims to evaluate Turkish dentists' awareness of and protective measures against COVID-19 infection.Methods: A web-based questionnaire consisting of 35 closed-ended and multiple-choice questions was prepared according to Turkish Dental Association guidelines. The questionnaire was divided into three domains: demographic data, precautionary measures, and attitude. Ethical clearance was obtained from the Istanbul University institutional review board. questionnaire was sent to the dentists registered with the Turkish Dental Association. The minimum sample size was calculated as 756 individuals. The Chi-Square test was used to evaluate the difference for categorical variables. Statistical significance was accepted as p< .05.Results: A total of nine hundred and ninety-seven questionnaires was analyzed. Five hundred and sixty-three respondents (56.5%) were general dentists, and 434 (43.5%) were specialists. Seven hundred and thirty-five (73.7%) dentists were found to wear disposable gowns, N95/FFP2 masks, and face shields. About half (48.1%) were confident of avoiding infection. Twenty-one (2.1%) subjects were SARS-Cov-2 positive. A majority of both dentists who had COVID-19 (71.4%) and dentists who did not have it (92.7%) agreed that COVID-19 is an occupational risk (p< .001).Conclusion: Although nearly two-thirds of the respondents reported using personal protective equipment, greater precautionary measures should be taken by dental staff to protect the patients from COVID-19 and other contagious diseases.Öğe Case series of ectodermal dysplasia and evaluation of oral findings: A literature review(2020) Gürcan, Aliye Tuğçe; Koruyucu, Mine; Seymen, Figen; Yardımcı, SılaEctodermal dysplasia (ED) is a hereditary disease characterized by anomalies in the structures of ectodermal origin. This report aims to determine the oral features of patients with ED syndrome and to present treatment approaches. Because of nutrition, speech and aesthetical problems due to the lack of teeth 22 patients with ED syndrome referred to faculty dentistry clinic. Facial physiognomy was typical for ED and the facial height was decreased due to the vertical dimension and the delalet exfoliation of primary teeth. Also anodontia, hypodontia, delayed eruption, diffuse enamel hypoplasia, conical tooth structure, talon cusps, microdontia, and, transposition in teeth were seen in patients. In most cases, prosthesis were applied to improve the facial aesthetics, speech and oral function due to the common hypodontia. The primary goals of the dental treatment of patients with ED are enhancing aesthetics and improving masticatory function. The oral rehabilitation of the patients’ needs multidisciplinary dental treatment.Öğe Clinical assessment of deleterious oral habits and dental caries–periodontal parameters among Turkish twins(Association for Dental Sciences of the Republic of China, 2023) İlisulu, Sabiha Ceren; Birant, Sinem; Kasimoglu, Yelda; Koruyucu, Mine; Tuna İnce, Elif Bahar; Seymen, FigenAbstract Background/purpose: Twin studies are crucial to assess the relative contribution of genetic and environmental factors. This study was conducted to evaluate association between deleterious oral habits and dental caries–periodontal parameters among Turkish twins. Materials and methods: The study comprised 143 pairs of dizygotic (DZ) twins and 59 pairs of monozygotic (MZ) twins aged 3–15 years. Twins were examined for dental caries, plaque index, gingival index, bleeding on probing and deleterious oral habits. Mann Whitney U test was used to examine the data. Results: The MZ twin pairs consisted of 60 male and 58 female twin pairs, whereas the DZ twin pairs consisted of 144 male and 142 female. The mean age of the twins was 9.63 ± 3.0 in MZ twins and 9.47 ± 3.2 in DZ twins. The mean DMFS value of MZ twins with bruxism is higher than those of MZ twins without bruxism (P = 0.001). The mean DMFS value of DZ twins with pacifier sucking is lower than those without (P = 0.007). A statistically significant difference was found between MZ twins with and without nail biting in terms of bleeding on probing and dmfs values (P = 0.035; P = 0.012). The mean values of the plaque index increased due to the mouth breathing in DZ twins (P = 0.024). Regarding the bleeding on probing, there was a statistically significant difference between MZ twins with and without atypical swallowing (P = 0.016). Conclusion: These findings suggest that dental caries–periodontal parameters are similarly affected by deleterious oral habits in MZ and DZ twins.Öğe Effects of Fixed and Removable Space Maintainers on Dental Plaque and DMFT/dft Values(Univ Costa Rica, Fac Odontologia, 2021) Gurcan, Aliye Tugce; Koruyucu, Mine; Kuru, Sinem; Sepet, Elif; Seymen, FigenPurpose: Space maintainers are important for the health and placement of children's primary and permanent teeth. However, plaque and caries levels can be negatively affected when a dental appliance is in the mouth. This study aims to evaluate the oral health of pediatric patients that have space maintainers applied as a result of early tooth loss. Methods: This study included 100 systemically healthy patients between the ages of 4-15 years that were treated with space maintainers due to early loss of teeth. Decayed, missing, filled tooth index values and dental plaque status of the participants were recorded. Controls were performed in the 6th and 12th month. The index results were compared and evaluated statistically using ANOVA and paired-t-tests. Results: A total of 116 space maintainers, including 36 band and loops, 16 lingual arches, 21 palatal arches, 43 removable appliances, were evaluated in the study. Statistically significant differences were found between the pre-treatment and post-treatment index values (p<0.001). In the group of band and loops and removable space maintainers; the increases in DMFT/dft values of 6th month and 12th month according to initial DMFT/dft values were statistically significant (p<0.05). For plaque index, the increase in 12th month of all types of appliances were found statistically significant ( p<0.001). The greatest increase in plaque index level was seen in the teeth of patients that had been treated with a lingual arch. Conclusions: Incompatible space maintainers can lead to caries, increased plaque accumulation, demineralized areas, and periodontal problems. The accumulation of plaque and difficulty of cleaning the teeth, especially in the fixed space maintainers, negatively affects the health of teeth. For this reason, good oral hygiene should be provided to patients and controls should be regularly performed.Öğe Enamel defects in Acp4R110C/R110C mice and human ACP4 mutations(2022) Liang, Tian; Wang, Shih-Kai; Smith, Charles; Zhang, Hong; Hu, Yuanyuan; Seymen, Figen; Koruyucu, Mine; Kasımoğlu, Yelda; Kim, Jung-wook; Zhang, Chuhua; Saunders, Thomas L.; Simmer, James P.; Hu, Jan C-C.Human ACP4 (OMIM*606362) encodes a transmembrane protein that belongs to histidine acid phosphatase (ACP) family. Recessive mutations in ACP4 cause non-syndromic hypoplastic amelogenesis imperfecta (AI1J, OMIM#617297). While ACP activity has long been detected in developing teeth, its functions during tooth development and the pathogenesis of ACP4-associated AI remain largely unknown. Here, we characterized 2 AI1J families and identified a novel ACP4 disease-causing mutation: c.774_775del, p.Gly260Aspfs*29. To investigate the role of ACP4 during amelogenesis, we generated and characterized Acp4R110C mice that carry the p.(Arg110Cys) loss-of-function mutation. Mouse Acp4 expression was the strongest at secretory stage ameloblasts, and the protein localized primarily at Tomes' processes. While Acp4 heterozygous (Acp4+/R110C) mice showed no phenotypes, incisors and molars of homozygous (Acp4R110C/R110C) mice exhibited a thin layer of aplastic enamel with numerous ectopic mineralized nodules. Acp4R110C/R110C ameloblasts appeared normal initially but underwent pathology at mid-way of secretory stage. Ultrastructurally, sporadic enamel ribbons grew on mineralized dentin but failed to elongate, and aberrant needle-like crystals formed instead. Globs of organic matrix accumulated by the distal membranes of defective Tomes' processes. These results demonstrated a critical role for ACP4 in appositional growth of dental enamel probably by processing and regulating enamel matrix proteins around mineralization front apparatus.Öğe Erken çocukluk döneminde travmatik diş yaralanmalarının, maloklüzyonların ve diş çürüğünün ağız sağlığı ile ilişkili yaşam kalitesi üzerine etkisi(2021) Gürcan, Aliye Tuğçe; Koruyucu, Mine; Bayram, Merve; Seymen, FigenAmaç: Bu çalışmanın amacı, travmatik diş yaralanmalarının (TDY) ve diş çürüğünün okul öncesi çocukların Ağız Sağlığı ile İlişkili Yaşam Kalitesi (OHRQoL) üzerindeki etkisini değerlendirmektir. Gereç ve Yöntemler: Ağız Sağlığı ile İlişkili Yaşam Kalitesini ölçmek için 206 okul öncesi çocuğun velisine 13 soruluk Erken Çocukluk Çağı Ağız Sağlığı Etki Ölçeği (ECOHIS) uygulanmıştır. Çocukların travmatik diş yaralanmaları, diş çürüğü (dmft skorları) ve ön bölge maloklüzyon özelliklerine bakılmıştır. Bulgular: Çocukların yaş ortalaması 4.09 ± 0.97 bulunmuştur. Diş çürüğü, Ağız Sağlığı ile İlişkili Yaşam Kalitesi üzerinde olumsuz bir etki göstermiştir. Diş çürüğü; Ağız Sağlığı ile İlişkili Yaşam Kalitesi ortalaması, semptomları, fonksiyonu, psikolojisi, ailesel sıkıntı ve aile fonksiyon alanları üzerinde olumsuz bir etki göstermiştir. Ön bölgede maloklüzyon varlığı sadece sosyal etkileşim alanı üzerinde olumsuz bir etki göstermiştir. Komplike travmatik diş yaralanmaları, komplike olmayan travmatik diş yaralanmalarına göre semptomlar açısından daha olumsuz bir etki göstermiştir. Sonuç: Travmatik dental yaralanma ve maloklüzyon gözlenen dişin varlığı, okul öncesi çocukların Ağız Sağlığı ile İlişkili Yaşam Kalitesi üzerinde yalnızca çocuk alanında olumsuz bir etkiye sahiptir; ancak, diş çürüğü, hem çocuk alanında hem aile alanında Ağız Sağlığı ile İlişkili Yaşam Kalitesi ile güçlü bir ilişkiye sahiptir.Öğe Evaluation of parents’ approaches to dental treatment during the COVID-19 pandemic in İstanbul/Türkiye: cross-sectional research(2023) Koruyucu, Mine; Kasımoğlu, Yelda; Baysan, Caner; İlisulu, Sabiha Ceren; Seymen, FigenABS TRACT Objective: Due to the transmission of coronavirus by particle or droplet, diagnosis and treatment of dental problems during the pandemic period in dental settings has been seen as a direct infection risk. This study aimed to compare parents’ approach to dental treatment with their educational background during the coronavirus disease-2019 (COVID-19) outbreak in İstanbul. Material and Methods: The parents were invited to answer the questionnaire via electronic form. The questionnaire form consists of 3 parts: (i) the sociodemographic characteristics of the parents (age, gender, educational level and number of children) (ii) parents’ behaviors, risk perceptions and knowledge levels during the COVID-19 pandemic (iii) parents’ approaches to dental treatment during the pandemic period (risk perceptions, behaviors and attitudes). The data was evaluated through the SPSS 25.0 statistical package program. Chi-square, Fisher’s exact, Bonferroni correction and student t-tests were used to evaluate the difference for categorical variables (p<0.05). Results: Response rate was 73.2% (366 parents). The average age of parents is 28.76. Parents with university or higher education level preferred not to go out as a precaution in the pandemic compared to parents with high school or less education level (p=0.044). When their children had toothache complaints during the pandemic period, the situation of taking them to the dentist was statistically significant and higher in parents with a university or higher education level (p=0.003). Conclusion: All these evaluations show that people with a high level of education have behaved more sensitive in terms of both virus protection and dental treatment behaviors during the pandemic period.Öğe FAM20A mutations and transcriptome analyses of dental pulp tissues of enamel renal syndrome(2023) Wang, Shih-Kai; Zhang, Hong; Wang, Yin-Lin; Lin, Hung-Ying; Seymen, Figen; Koruyucu, Mine; Wright, J. Timothy; Kim, Jung-Wook; Simmer, James P.; Hu, Jan C-C.Aim: Biallelic loss-of-function FAM20A mutations cause amelogenesis imperfecta (AI) type IG, better known as enamel renal syndrome (ERS), characterized by severe enamel hypoplasia, delayed/failed tooth eruption, intrapulpal calcifications, gingival hyperplasia, and nephrocalcinosis. FAM20A binds to FAM20C, the Golgi casein kinase (GCK), and potentiates its function to phosphorylate secreted proteins critical for biomineralization. While many FAM20A pathogenic mutations have been reported, the pathogeneses of orodental anomalies in ERS remain to be elucidated. This study aimed to identify disease-causing mutations for patients with ERS phenotypes and to discern the molecular mechanism underlying ERS intrapupal calcifications. Methodology: Phenotypic characterization and whole exome analyses were conducted for 8 families and 2 sporadic cases with hypoplastic AI. A minigene assay was performed to investigate the molecular consequences of a FAM20A splice-site variant. RNA sequencing followed by transcription profiling and gene ontology (GO) analyses were carried out for dental pulp tissues of ERS and the control. Results: Biallelic FAM20A mutations were demonstrated for each affected individual, including 7 novel pathogenic variants: c.590-5T>A, c.625T>A (p.Cys209Ser), c.771del (p.Gln258Argfs*28), c.832_835delinsTGTCCGACGGTGTCCGACGGTGTCCA (p.Val278Cysfs*29), c.1232G>A (p.Arg411Gln), c.1297A>G (p.Arg433Gly), and c.1351del (p.Gln451Serfs*4). The c.590-5T>A splice-site mutation caused Exon 3 skipping, which resulted in an in-frame deletion of a unique region of the FAM20A protein, p.(Asp197_Ile214delinsVal). Analyses of differentially expressed genes in ERS pulp tissues demonstrated that genes involved in biomineralization, particularly dentinogenesis, were significantly upregulated, such as DSPP, MMP9, MMP20, and WNT10A. Enrichment analyses indicated over-representation of gene sets associated with BMP and SMAD signaling pathways. In contrast, GO terms related to inflammation and axon development were under-represented. Among BMP signaling genes, BMP agonists GDF7, GDF15, BMP3, BMP8A, BMP8B, BMP4, and BMP6 were upregulated, while BMP antagonists GREM1, BMPER, and VWC2 showed decreased expression in ERS dental pulp tissues. Conclusions: Upregulation of BMP signaling underlies intrapulpal calcifications in ERS. FAM20A plays an essential role in pulp tissue homeostasis and prevention of ectopic mineralization in soft tissues. This critical function probably depends upon MGP (matrix Gla protein), a potent mineralization inhibitor that must be properly phosphorylated by FAM20A-FAM20C kinase complex.Öğe İkizlerde Genetik Ve Çevresel Faktörlerin Dental Bulgulara Etkisi(2018) Seymen, Figen; Karacan, İlker; Tuna İnce, Elif Bahar; Gençay, Koray; Nursen Topcuoğlu, Emine; Koruyucu, Mine; Birant, SinemDiş çürüklerinin ortaya çıkmasında genetiğin rolü önemlidir, hastalığın %30-60 arasında kalıtsal yatkınlık ile oluştuğu bildirilmektedir. Bu amaçla, ikizlerde ağız diş sağlığını ilgilendiren klinik bulgular detaylı bir muayene ile değerlendirilerek kardeşler arasında farklılıkların olup olmadığının belirlenmesi, genetik ve metagenomik analizler ile de ağız diş sağlığını ilgilendiren klinik parametreler ile çürük genetiği üzerine aday genlerin ve mikroorganizmaların etkilerinin incelenmesi hedeflenmiştir. Çalışmaya, İstanbul Üniversitesi Diş Hekimliği Fakültesi Pedodonti Anabilim Dalı?na ilk muayene için başvuran 3-15 yaş aralığındaki (ort. yaş 9,64±3,28) 404 birey (143 çift yumurta ikizi, 59 tek yumurta ikizi) dahil edilmiştir. Aileden detaylı anamnez alınarak çocukların doğum haftası, doğum boyu ve kilosu kaydedilmiştir. Klinik muayene ile ağız kokusu varlığı, çürük veya dolgulu dişlerin oranı, periodontal bulgular, dişlerdeki eroziv/hipomineralize/hipokalsifiye lezyonlar, ve dental anomaliler belirlenmiştir. Maloklüzyona neden olabilecek kötü ağız alışkanlıkları (parmak emme, ağızdan solunum, biberon emzik kullanımı, tırnak yeme, atipik yutkunma), eklem problemleri ve bruksizm hakkında veliye sorular sorulmuştur. Radyografik muayene ile çocukların büyüme gelişim yaşı ve dişlere ait anomaliler değerlendirilmiştir. Çalışma modelleri üzerinden dişlerin büyüklükleri, ark boyu ve diş boyu ölçümleri yapılmıştır. Çalışma kapsamında bireylerin steril tek kullanımlık tükürük kaplarına tükürmeleri sağlanmıştır. Alınan tükürük örneklerinden DNA izolasyonu yapıldıktan sonra diş çürüğüne neden olduğu literatürlerde belirtilen genlerin markırları PCR?da incelenerek mutasyonlar tespit edilmiştir. Bu analizin sonucuna göre çürük yapıcı genlerin metagenomik incelenmesi ile rastgele seçilmiş bireylerde oral profil değerlendirilmiştir. Çalışmada elde edilen bulgular değerlendirilirken, istatistiksel analizler için SPSS22 programı kullanılmıştır. Çalışma verileri değerlendirilirken; Oneway, ANOVA, Kruskal Wallis, post hoc Tukey HSD testi, Mann Whithney U testi, Bonferroni testi, Friedman Testi, Wilcoxon işaret testi ve Fisher?s exact test kullanılmıştır. Sonuç olarak rs3796704 (ENAM) ve rs3828054 (TUFT1) SNP?lerinin çürük ile ilişkili olduğu belirlenmiştir. Gruplarda diş çürüğü olan, olmayan ya da kardeşlerin sadece birisinde diş çürüğü bulunan ikizlerde ise hem ağırlıklandırılmamış hem de ağırlıklandırılmış UniFrac metrik hesabına göre gruplar arasında mikrobiyom benzerliği açısından anlamlı farklılıklar bulunmamıştır.Öğe Investigation of the self-reported attitude of dentists towards preventive applications(2023) Koruyucu, Mine; Özcan, Hazal; Birant, Sinem; İlisulu, Sabiha Ceren; Bekiroglu, Nural; Seymen, FigenThe purpose of this study was to determine the approaches of dentists to the use of fluoride applications as preventive treatment options. The study was a questionnaire based cross-sectional survey divided into two sections and the participating dental practitioners were asked to answer a questionnaire about: (i) demographic data and (ii) dentists' attitudes to prevention. Data entry and analyses were performed using SPSS statistical software. Data were analyzed using frequency counts, percentages, and Chi-square test. The sample (N=481), who volunteered to participate, consisted of 332 general dentists (69%) and 149 specialist dentists (31%). 380 (79%) dentists applied preventive applications. 452 dentists (94%) considered that fluoride was effective in preventing caries. 235 dentists (48.9%) thought that fluoride had side effects. Significantly more female dentists thought that fluoride had a caries preventive effect than male dentists (p=0.005) and they applied preventive treatments more frequently than male dentists (p=0.01). All age groups believed that fluoride was useful to prevent caries, and almost all the dentists in the 18-25 age range believed in a caries preventive effect of fluoride (98.6%) (p=0.0001). Dentists in 18-25 age range used preventive applications for their patients more than other age groups (p=0.019). Fewer dentists aged 26-35 than dentists in the other age groups (p=0.037) thought that the fluoride preparations had dental and/or medical side effects. Non-specialist dentists gave more priority to preventive applications than specialist dentists (p=0.0001). The approach of dentists to the use of preventive practices will change if they keep up-todate with information about preventive practices through ongoing training.Öğe Novel WDR72 mutations causing hypomaturation amelogenesis imperfecta(2023) Kim, Youn Jung; Zhang, Hong; Lee, Yejin; Seymen, Figen; Koruyucu, Mine; Kasımoğlu, Yelda; Simmer, James P.; Hu, Jan C-C; Kim, Jung-WookAmelogenesis imperfecta (AI) is a heterogeneous collection of hereditary enamel defects. The affected enamel can be classified as hypoplastic, hypomaturation, or hypocalcified in form. A better understanding of normal amelogenesis and improvements in our ability to diagnose AI through genetic testing can be realized through more complete knowledge of the genes and diseasecausing variants that cause AI. In this study, mutational analysis was performed with whole exome sequencing (WES) to identify genetic etiology underlying the hypomaturation AI condition in affected families. Mutational analyses identified biallelic WDR72 mutations in four hypomaturation AI families. Novel mutations include a homozygous deletion and insertion mutation (NM_182758.4: c.2680_2699delinsACTATAGTT, p.(Ser894Thrfs*15)), compound heterozygous mutations (paternal c.2332dupA, p.(Met778Asnfs*4)) and (maternal c.1287_1289del, p.(Ile430del)) and a homozygous 3694 bp deletion that includes exon 14 (NG_017034.2:g.96472_100165del). A homozygous recurrent mutation variant (c.1467_1468delAT, p.(Val491Aspfs*8)) was also identified. Current ideas on WDR72 structure and function are discussed. These cases expand the mutational spectrum of WDR72 mutations causing hypomaturation AI and improve the possibility of genetic testing to accurately diagnose AI caused by WDR72 defects.Öğe Path analysis of the relationships between the eruption time of the first primary teeth and various factors in twins(MDPI, 2023) Birant, Sinem; Veznikli, Mert; Kasımoğlu, Yelda; Koruyucu, Mine; Evren, Atıf Ahmet; Seymen, FigenThe timing of primary tooth eruption is critical for children’s health planning and the diagnosis of specific growth disorders. The purpose of this study is to assess the relationship between twin pairs’ birth weight, gestational age, and gender, which are indicators of prenatal factors; breast-feeding duration, which is an indicator of postnatal factors; type of delivery, which is an indicator of maternal as well as genetic factors; and age of the primary tooth. Twin children aged from 3 to 15 years who applied to the clinic for the first dental examination constituted the sample group. In this twin study, 59 monozygotic (MZ) twin pairs and 143 dizygotic (DZ) twin pairs were included. Genetic (MZ vs. DZ), maternal (type of delivery, gestational age), perinatal (birth weight, gender), and postnatal (duration of breastfeeding) information was obtained, and effects on the children’s Eruption Timing of the First Primary Tooth (ETFPT) were examined. Statistical analysis was performed using the consistent partial least squares structural equation model (robust PLSc) technique. As birth weight increased, the age at first eruption became younger, but this change was different between MZ and DZ twins (p < 0.05). While the age at first tooth eruption was older in identical twins who were breastfed for the first 6 months, this increase was not observed in DZ twins. The mean of ETFPT was calculated as 7.31 months in MZ twins and 6.75 months in DZ twins. The effect of breastfeeding and birth weight on ETFPT may differ according to zygosity in twins. MZ twins may tend to take longer to experience the eruption of their first primary teeth.Öğe Phenotypic variability in LAMA3-associated amelogenesis imperfecta(2022) Wang,Shih-Kai; Zhang, Hong; Wang, Yin-Lin; Seymen, Figen; Koruyucu, Mine; Simmer, James P.; Hu, Jan C-CObjective: Amelogenesis imperfecta (AI) is defined as inherited enamel malformations. LAMA3 (laminin alpha-3) encodes a critical protein component of the basement membrane (laminin-332). Individuals carrying heterozygous LAMA3 mutations have previously been shown to have localized enamel defects. This study aimed to define clinical phenotypes and to discern the genetic etiology for four AI kindreds. Materials and methods: Whole exome analyses were conducted to search for sequence variants associated with the disorder, and micro-computed tomography (μCT) to characterize the enamel defects. Results: The predominant enamel phenotype was generalized thin enamel with defective pits and grooves. Horizonal bands of hypoplastic enamel with chalky-white discoloration and enamel hypomineralization were also observed and demonstrated by μCT analyses of affected teeth. Four disease-causing LAMA3 mutations (NM_198129.4:c.3712dup; c.5891dup; c.7367del; c.9400G>C) were identified. Compound heterozygous MMP20 mutations (NM_004771.4:c.539A>G; c.692C>T) were also found in one proband with more severe enamel defects, suggesting a mutational synergism on disease phenotypes. Further analyses of the AI-causing mutations suggested that both α3A (short) and α3B (long) isoforms of LAMA3 are essential for enamel formation. Conclusions: Heterozygous LAMA3 mutations can cause generalized enamel defects (AI1A) with variable expressivity. Laminin-332 is critical not only for appositional growth but also enamel maturation.Öğe The modified shields classification and 12 families with defined dspp mutations(2022) Seymen, Figen; Simmer, James P.; Zhang, Hong; Moon, Sophie J. H.; Donnelly, Lori A-J.; Lee, Yuan-Ling; Koruyucu, Mine; Chan, Hui-Chen; Lee, Kevin Y.; Wu, Suwei; Hsiang, Chia-Lan; Tsai, Anthony T. P.Mutations in Dentin Sialophosphoprotein (DSPP) are known to cause, in order of increasing severity, dentin dysplasia type-II (DD-II), dentinogenesis imperfecta type-II (DGI-II), and dentino-genesis imperfecta type-III (DGI-III). DSPP mutations fall into two groups: a 5′-group that affects protein targeting and a 3′-group that shifts translation into the −1 reading frame. Using whole-exome sequence (WES) analyses and Single Molecule Real-Time (SMRT) sequencing, we identified disease-causing DSPP mutations in 12 families. Three of the mutations are novel: c.53T>C/p.(Val18Ala); c.3461delG/p.(Ser1154Metfs*160); and c.3700delA/p.(Ser1234Alafs*80). We propose genetic analysis start with WES analysis of proband DNA to identify mutations in COL1A1 and COL1A2 causing dominant forms of osteogenesis imperfecta, 5′-DSPP mutations, and 3′-DSPP frameshifts near the margins of the DSPP repeat region, and SMRT sequencing when the disease-causing mutation is not identified. After reviewing the literature and incorporating new information showing distinct differences in the cell pathology observed between knockin mice with 5′-Dspp or 3′-Dspp mutations, we propose a modified Shields Classification based upon the causative mutation rather than phenotypic severity such that patients identified with 5′-DSPP defects be diagnosed as DGI-III, while those with 3′-DSPP defects be diagnosed as DGI-II.Öğe Translated mutant DSPP mRNA expression level impacts the severity of dentin defects(2022) Kim, Youn Jung; Lee, Yejin; Zhang, Hong; Seymen, Figen; Koruyucu, Mine; Bayrak, Şule; Tüloğlu, Nuray; Simmer, James P.; Hu, Jan C-C.; Kim, Jung-WookHereditary dentin defects are conventionally classified into three types of dentinogenesis imperfecta (DGI) and two types of dentin dysplasia (DD). Mutations in the dentin sialophospho protein (DSPP) gene have been identified to cause DGI type II and III and DD type II; therefore, these are not three different conditions, but rather allelic disorders. In this study, we recruited three families with varying clinical phenotypes from DGI-III to DD-II and performed mutational analysis by candidate gene analysis or whole-exome sequencing. Three novel mutations including a silent mutation (NM_014208.3: c.52-2del, c.135+1G>C, and c.135G>A; p.(Gln45=)) were identified, all of which affected pre-mRNA splicing. Comparison of the splicing assay results revealed that the expression level of the DSPP exon 3 deletion transcript correlated with the severity of the dentin defects. This study did not only expand the mutational spectrum of DSPP gene, but also advanced our understanding of the molecular pathogenesis impacting the severity of hereditary dentin defects.
