Epilepsi tanılı çocuk hastalarda genetik etiyolojinin hedeflenmiş yeni nesil dizi analizi verilerine dayanarak retrospektif olarak araştırılması
Küçük Resim Yok
Tarih
2022
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Epilepsi çocukların %0,5 ile %1'ini etkileyen tekrarlayan nöbetlerle karakterize multifaktöriyel bir hastalıktır. Etiyolojisinde çeşitli faktörler bulunmakla birlikte genetik faktörler etiyolojinin %40-50'sinde yer almaktadır. Son zamanlarda yeni nesil dizileme teknolojilerindeki gelişmeler sayesinde, epilepsili hastalarda etiyolojide çok sayıda moleküler değişik saptanmıştır. Bu da epilepsi hastalarında kesin etiyolojinin belirlenerek kişiselleştirilmiş tedavilerin önünü açmıştır. Bu tez çalışmasında epilepsi tanılı çocuk hastalarda hedeflenmiş NGS verileri retrospektif olarak incelenerek, epilepsi panelinin klinik karar verme üzerindeki etkisinin incelenmesi ve NGS sisteminin pediatrik epilepsi hastalarındaki tanı değerinin saptanması amaçlanmıştır. Gereç ve Yöntem: Bu tez çalışmasına İnönü Üniversitesi Tıp Fakültesi Tıbbi Genetik Polikliniği'nde 2018-2021 tarihleri arasında epilepsi tanısı ile değerlendirilen ve tanı testi olarak hedefli NGS analizleri yapılmış 107 çocuk hasta(0-18 yaş) dahil edildi. Çalışmada patojenik, muhtemel patojenik ve VUS varyantlar yer aldı. Elde edilen nedensel varyantlar ile NGS panelinin tanı değeri hesaplandı. Bulgular: Çalışmada 20 patojenik, 5 muhtemel patojenik ve 49 klinik önemi bilinmeyen olmak üzere 74 varyant saptandı. VUS varyantlar yeniden analiz edildikten sonra 15'i benign, 15'i muhtemel benign, 5'i muhtemel patojenik, 1'i patojenik olmak üzere 36 varyantın ACMG sınıflandırması tekrar belirlendi. Buna göre toplamda 31 patojenik-muhtemel patojenik (P, LP) ve 13 VUS varyant tespit edildi. Bu çalışmada, 110 epilepsi geni içeren NGS panelinin prediktif değeri %28 olarak hesaplandı. Sonuç: Çalışmamızda, epilepsi hastalarındaki hedefli yeni NGS analizinin tanısal değeri gu?ncel literatu?r verileriyle uyumlu olarak tespit edilmiştir. Olgularda NGS ile genetik etiyolojinin belirlenmesi prognozun tahmin edilmesi ve uygun tedavinin seçilmesine olanak sağlamaktadır. Anahtar Kelimeler: Epilepsi, gen paneli, yeni nesil dizileme
Aim: Epilepsy is a multifactorial disease which affects 0.5% to 1% of children and is characterized with recurrent seizures. Although various factors are shown to be responsible in its etiology; genetic factors are involved in 40-50% of the etiology. Numerous molecular changes have been identified in the etiology in patients with epilepsy by means of recent advances in NGS technologies. This paved the way for personalized treatments by determining the exact etiology in epilepsy patients. In this thesis study, it was aimed to examine the effect of the epilepsy panel on clinical decision making and to determine the diagnostic value of the NGS system in pediatric epilepsy patients by retrospectively examining the data of the targeted NGS panel in pediatric patients with epilepsy. Material and Method: In this thesis study, 107 pediatric patients(0-18 years old), who were evaluated with the diagnosis of epilepsy in İnönü University Faculty of Medicine Medical Genetics Polyclinic between 2018-2021 and to whom targeted NGS analyzes was performed for diagnosis, were included. The study included variants that are pathogenic, LP, and of VUS. The diagnostic value of the NGS panel was calculated with the obtained causal variants. Findings: In the study, 74 variants were detected, of which 20 were pathogenic, 5 were LP, and 49 were of VUS. After reanalysis of VUS variants, the ACMG classification of 36 variants, including 15 benign, 15 likely benign, 5 LP, and 1 pathogenic, were redefined. Accordingly, a total of 31 P, LP and 13 VUS variants were detected. In this study, the predictive value of the NGS panel containing 110 epilepsy genes was calculated as 28%. Conclusion: In our study, the diagnostic value of targeted NGS analysis in epilepsy patients was determined in accordance with current literature data. Identification of genetic etiology with NGS in cases allows prediction of prognosis and selection of appropriate treatment. Keywords: Epilepsy, gene panel, next generation sequencing
Aim: Epilepsy is a multifactorial disease which affects 0.5% to 1% of children and is characterized with recurrent seizures. Although various factors are shown to be responsible in its etiology; genetic factors are involved in 40-50% of the etiology. Numerous molecular changes have been identified in the etiology in patients with epilepsy by means of recent advances in NGS technologies. This paved the way for personalized treatments by determining the exact etiology in epilepsy patients. In this thesis study, it was aimed to examine the effect of the epilepsy panel on clinical decision making and to determine the diagnostic value of the NGS system in pediatric epilepsy patients by retrospectively examining the data of the targeted NGS panel in pediatric patients with epilepsy. Material and Method: In this thesis study, 107 pediatric patients(0-18 years old), who were evaluated with the diagnosis of epilepsy in İnönü University Faculty of Medicine Medical Genetics Polyclinic between 2018-2021 and to whom targeted NGS analyzes was performed for diagnosis, were included. The study included variants that are pathogenic, LP, and of VUS. The diagnostic value of the NGS panel was calculated with the obtained causal variants. Findings: In the study, 74 variants were detected, of which 20 were pathogenic, 5 were LP, and 49 were of VUS. After reanalysis of VUS variants, the ACMG classification of 36 variants, including 15 benign, 15 likely benign, 5 LP, and 1 pathogenic, were redefined. Accordingly, a total of 31 P, LP and 13 VUS variants were detected. In this study, the predictive value of the NGS panel containing 110 epilepsy genes was calculated as 28%. Conclusion: In our study, the diagnostic value of targeted NGS analysis in epilepsy patients was determined in accordance with current literature data. Identification of genetic etiology with NGS in cases allows prediction of prognosis and selection of appropriate treatment. Keywords: Epilepsy, gene panel, next generation sequencing
Açıklama
Anahtar Kelimeler
Genetik, Genetics, Nöroloji
