Turner sendromu 45x0 tanılı olgularda mikroarray çalışması ile kopya sayısı değişiklikleri saptanması ve klinik varyasyonlar ile ilişkilendirilmesi
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Dosyalar
Tarih
2020
Yazarlar
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Yayıncı
Ege Üniversitesi, Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Turner Sendromu (TS), yaklaşık olarak 2500 canlı doğumda bir görülme sıklığı ile, en sık görülen kromozom anomalilerinden birisidir. Boy kısalığı ve primer over yetmezliği TS'nun en önemli iki karakteristik bulgusudur. Yele boyun, düşük ense saç çizgisi, kubitus valgus TS olgularında görülen diğer karakteristik özelliklerdir. Olgular ağır kardiyak ve renal anomaliler taşıyabilir. Otoimmünite ve tip 2 diyabet açısından normal popülasyona göre daha risklidirler. Karyotip monozomi X, mozaik yapı ve X kromozomu yapısal anomalilerini içeren şekillerde çok farklı olabilir. Genotipik ve fenotipik özellikler olgular arasında farklılık göstermektedir. Amaç: Bu çalışma, TS olgularında görülen klinik varyasyonları, mikroarray çalışmasıyla saptanacak olası kopya sayısı değişiklikleri (CNV) ile ilişkilendirmeyi amaçlamıştır. Gereç ve Yöntem: Aralık 2018-Mayıs 2020 tarihleri arasında, Ege Üniversitesi Çocuk Genetik Hastalıkları ve Pediatrik Endokrinoloji Bilim Dalı'nda takipli 0-18 yaş arasında TS tanılı 53 olgu çalışmaya dahil edildi. Bu olgulardan 36'sından mikroarray çalışması için kan alınarak, mikroarray sonuçları ile olguların klinik özellikleri arasında anlamlı bir ilişki olup olmadığı araştırıldı. Bulgular: Olguların 33'ü 45,X, 7'si 45,X/46,XX, 6'sı 45,X/46,Xi(Xq), 2'si 46,Xi(Xq), 2'si 45,X/46,r(X), 1'i 45,X/46,Xi(Xp), 1'i 45,X/46,XY, 1'i 45,X/46,X+mar(idicY) karyotip yapısında saptandı. Çalışmamızda TS olgularında en sık görülen klinik bulgu %90 görülme sıklığı ile boy kısalığıydı. Ayrık yerleşimli meme başı bulgusu %71.1 görülme oranı ile ikinci en sık bulguydu. Literatür ile uyumlu olarak, olguların 22'sinde (%41.5) kardiyak anomali saptandı; en sık görülen biküspit aortik kapak anomalisiydi. Olguların 14'ünde (%26.4) renal anomali saptandı; en sık görülen at nalı böbrek anomalisiydi. Literatürden farklı olarak bu iki majör klinik bulgu ile olguların karyotip sonuçları arasında istatistiksel anlamlı bir ilişki bulunmadı. Karyotip grupları ile olguların FSH değerleri arasında anlamlı ilişki bulundu (p=0.034). Monozomi X ve mozaik izokromozom Xq olgularında FSH değeri, 45,X/46,XX mozaik karyotipi taşıyan olgulara göre, belirgin yüksek saptandı. Mikroarray çalışması yapılan 36 olgudan, 8'inde kopya sayısı değişiklikleri saptandı. Sonuç: Kopya sayısı değişikliği saptanan 8 olguda TS kliniğinde beklenmeyen atipik bulgular saptanmıştır. Klinik varyasyonlar açısından zengin olan TS'da genotip fenotip ilişkilerini açıklamak için, atipik bulguları olan olgularda mikroarray çalışması yapılması önerilir.
ABSTRACT Turner Syndrome (TS) is one of the most common chromosomal abnormalities, with an incidence of approximately one in 2500 live births. Short stature and primary ovarian incuficiency are the two most important characteristic findings of TS. Webbed neck, low set hairline, cubitus valgus are other characteristic features of TS cases. Cases may have severe cardiac and renal anomalies. And they are more risky in terms of autoimmunity and type 2 diabetes than the normal population. The karyotype can vary that include monosomy X, mosaic structure and X chromosome structural anomalies. Genotypic and phenotypic characteristics differ between cases. Objective: This study aimed to correlate the clinical variations seen in TS cases with possible copy number changes that can be detected by microarray study. Materials and methods: Fifty three patients diagnosed with TS, between the ages of 0-18 who were followed up in Ege University Pediatric Genetic Diseases and Pediatric Endocrinology Departments between December 2018 and May 2020 were included in the study. Blood samples were taken from 36 of these cases for microarray study. Results: Karyotypes were as follows; thirty-three of cases were 45,X, 7 were 45,X/46,XX, 6 were 45,X/46,Xi(Xq), 2 were 46,Xi(Xq), 2 were 45,X/46,r(X), one was 45,X/46,Xi(Xp), one was 45,X/46,XY, and one was 45,X/46,X+mar(idicY) karyotype. İn this study the most common clinical finding in TS cases was short stature with a 90% incidence. İnverted nipple was the second most common finding with an incidence of 71.1%. Consistent with the literature, cardiac anomalies were detected in 22 (41.5%) of cases, and the most common was bicuspit aortic valve anomaly. Renal anomaly was found in 14 (26.4%) of cases, and the most common was horseshoe kidney anomaly. Unlike the literature there was no statistically significant relationship between these two major clinical findings and the karyotype results of the cases. A significant correlation was found between karyotype groups and FSH values of the cases (p=0.034). İn monosomy X and mosaic isochromosome Xq cases, the FSH value was found to be significantly higher than those with 45,X/46,XX mosaic karyotype. Copy number variations were found in 8 out of 36 cases whose microarray study was performed. Conclusion: Copy number changes were detected in 8 patients with unexpected atipycal findings. In order to explain the genotype-phenotype relationships in TS, which has a wide range of clinical findings, microarray analysis is recommended in cases with atypical findings.
ABSTRACT Turner Syndrome (TS) is one of the most common chromosomal abnormalities, with an incidence of approximately one in 2500 live births. Short stature and primary ovarian incuficiency are the two most important characteristic findings of TS. Webbed neck, low set hairline, cubitus valgus are other characteristic features of TS cases. Cases may have severe cardiac and renal anomalies. And they are more risky in terms of autoimmunity and type 2 diabetes than the normal population. The karyotype can vary that include monosomy X, mosaic structure and X chromosome structural anomalies. Genotypic and phenotypic characteristics differ between cases. Objective: This study aimed to correlate the clinical variations seen in TS cases with possible copy number changes that can be detected by microarray study. Materials and methods: Fifty three patients diagnosed with TS, between the ages of 0-18 who were followed up in Ege University Pediatric Genetic Diseases and Pediatric Endocrinology Departments between December 2018 and May 2020 were included in the study. Blood samples were taken from 36 of these cases for microarray study. Results: Karyotypes were as follows; thirty-three of cases were 45,X, 7 were 45,X/46,XX, 6 were 45,X/46,Xi(Xq), 2 were 46,Xi(Xq), 2 were 45,X/46,r(X), one was 45,X/46,Xi(Xp), one was 45,X/46,XY, and one was 45,X/46,X+mar(idicY) karyotype. İn this study the most common clinical finding in TS cases was short stature with a 90% incidence. İnverted nipple was the second most common finding with an incidence of 71.1%. Consistent with the literature, cardiac anomalies were detected in 22 (41.5%) of cases, and the most common was bicuspit aortic valve anomaly. Renal anomaly was found in 14 (26.4%) of cases, and the most common was horseshoe kidney anomaly. Unlike the literature there was no statistically significant relationship between these two major clinical findings and the karyotype results of the cases. A significant correlation was found between karyotype groups and FSH values of the cases (p=0.034). İn monosomy X and mosaic isochromosome Xq cases, the FSH value was found to be significantly higher than those with 45,X/46,XX mosaic karyotype. Copy number variations were found in 8 out of 36 cases whose microarray study was performed. Conclusion: Copy number changes were detected in 8 patients with unexpected atipycal findings. In order to explain the genotype-phenotype relationships in TS, which has a wide range of clinical findings, microarray analysis is recommended in cases with atypical findings.
Açıklama
Anahtar Kelimeler
Turner Sendromu, Mikroarray, Kopya Sayısı Değişiklikleri, Klinik Varyasyonlar, Turner Syndrome, Copy Number Variations, Microarray, Clinical Variations
