Turkiye Klinikleri Journal of Medical Sciences

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5 Alfa Redüktaz Tip 2 Enzim Eksikliği Olan Hastalarda SRD5A2 Geni Metilasyon Değişikliklerinin Araştırılması
Investigation of Methylation Alterations on SRD5A2 Gene in Patients with 5 Alpha Reductase Type 2 Enzyme Deficiency
Emre KIRATa, Aysel KALAYCI YİĞİNa, Filiz ÖZDEMİRa, Mehmet SEVENa
aİstanbul Üniversitesi-Cerrahpaşa, Cerrahpaşa Tıp Fakültesi, Tıbbi Genetik ABD, İstanbul, TÜRKİYE
Turkiye Klinikleri J Med Sci. 2020;40(1):68-73
doi: 10.5336/medsci.2019-71954
Article Language: TR
Full Text
ÖZET
 Amaç: 5 alfa redüktaz Tip 2 enzim eksikliği; erkek genotipli (46,XY) bireylerde cinsel gelişim bozukluğuna neden olan, otozomal resesif kalıtılan bir hastalıktır. 5 alfa redüktaz Tip 2 enzim eksikliği düşünülen hastalarda en önemli tanı yöntemi genital cilt fibroblast kültürü enzim analizidir. Ancak, pratikte kesin tanı SRD5A2 (Steroid 5 alfa redüktaz alfa polipeptid 2) geni mutasyon analizi ile konulmaktadır. Klinik bulgular 5 alfa redüktaz Tip 2 enzim eksikliğini düşündürmesine rağmen, hastaların bir kısmında dizi analizi ile mutasyon tespit edilememektedir. Bu çalışmada, 5 alfa redüktaz Tip 2 enzim eksikliği ön tanısıyla izlenen ve SRD5A2 geninde dizi analizi ile mutasyon tespit edilmeyen hastalarda metilasyon değişikliklerinin incelenmesi ve mevcut hastalıkla metilasyon değişiklikleri arasında bir ilişki olup olmadığının belirlenmesi amaçlandı. Gereç ve Yöntemler: 5AR2E ön tanısı alan, 46,XY genotipine sahip, dış genital anomalisi olan, beta insan koryonik gonadotropini uyarısına normal testosteron yanıtı veren, testosteron/dihidrotestosteron oranı 8`in üzerinde tespit edilen ve SRD5A2 geninde mutasyon saptanmayan hastalar ile değişik nedenlerle polikliniğimize başvuran 12 sağlıklı ve gönüllü birey kontrol grubu olarak çalışmaya dâhil edildi. Bulgular: Hasta grubunun SRD5A2 genindeki 6 adet CpG adacığının metilasyon oranları, kontrol grubu ile karşılaştırıldığında daha yüksek bulundu ve DNA metilasyonunun SRD5A geninin düzenlenmesinde rol oynayabileceği gösterildi. Sonuç: Değişik nedenlerle genital cilt fibroblast kültüründe enzim analizi yapılamayan ve DNA dizi analizinde mutasyon bulunmayan bu hastalarda, metilasyon değişikliklerinin de değerlendirilmesinin hastalığın genetik etiyolojisinin aydınlatılmasında yararlı olacağı düşünülmektedir.

Anahtar Kelimeler: Cinsel gelişim bozukluğu; SRD5A2 geni; epigenetik
ABSTRACT
 Objective: 5 alpha reductase Type 2 enzyme deficiency is an autosomal recessive inherited disease that causes sexual development disorder in individuals with male genotype (46,XY). Genital skin fibroblast culture enzyme analysis is the most important diagnostic method in patients with 5 alpha reductase Type 2 enzyme deficiency. However, definitive diagnosis is made by SRD5A2 (Steroid 5 alpha reductase alpha polypeptide 2) gene mutation analysis. Although clinical findings suggest 5 alpha reductase Type 2 enzyme deficiencies, mutation cannot be detected by sequence analysis in some patients. The aim of this study was to investigate the methylation changes in patients with a pre-diagnosis of 5 alpha reductase Type 2 enzyme deficiency and who were not found mutations by sequence analysis in SRD5A2 gene and to determine whether there was a relationship between methylation changes and current disease. Material and Methods: Patients with a pre-diagnosis of 5AR2E, 46,XY genotype, external genital anomaly, normal testosterone response to beta human chorionic gonadotropin stimulation, testosterone/dihydrotestosterone ratio higher than 8 and no mutation in SRD5A2 gene and 12 healthy and volunteer individuals who applied to our outpatient clinic for various reasons as the control group were included in the study. Results: Methylation rates of 6 CpG islands in SRD5A2 gene were higher in the patient group than the control group. So this showed that the DNA methylation can plays a role in the regulation of the SRD5A gene. Conclusion: It is considered that the evaluation of methylation changes in these patients who cannot be analyzed in genital skin fibroblast culture due to various reasons and without mutations in DNA sequence analysis will be useful in elucidating the genetic etiology of the disease.

Keywords: Disorders of sexual development; SRD5A2 gene; epigenetics
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