Turkiye Klinikleri Journal of Medical Sciences

.: ORIGINAL RESEARCH
Tüm Ekzom Dizileme Verilerinde İkincil Bulguların Retrospektif Olarak Değerlendirilmesi
Retrospective Evaluation of Secondary Findings in Whole Exome Sequencing Data
Özgür BALASARa , Müşerref BAŞDEMİRCİa
aKonya Şehir Hastanesi, Tıbbi Genetik Kliniği, Konya, Türkiye
Turkiye Klinikleri J Med Sci. 2024;44(2):91-6
doi: 10.5336/medsci.2024-101344
Article Language: TR
Full Text
ÖZET
 Amaç: Tüm ekzom dizileme [whole exome sequencing (WES)], etiyolojisinde genetik ve klinik heterojenite gösteren hastalıkların tanısında kullanılan etkili bir moleküler yöntemdir. Ayrıca bu yöntem ile hastanın genetik teste tabi tutulmasına neden olan birincil hastalık dışında, ikincil bulgu olarak adlandırılan, yaşamı tehdit eden veya önlenebilir hastalığa neden olan genlerdeki değişiklikler de tespit edilebilir. Bu çalışmanın amacı, WES uygulanan hastalarda ikincil bulguların sıklığını araştırmaktır. Gereç ve Yöntemler: Çalışma retrospektif bir çalışmadır, 113 erkek ve 103 kadın olmak üzere toplam 216 hastanın WES verileri ikincil bulgular açısından Amerikan Tıbbi Genetik ve Genomik Koleji [American College of Medical Genetics and Genomics (ACMG)] SF v3.2 tavsiyelerine göre araştırıldı. İlgili genlerdeki patojenik ve olası patojenik varyantlar çalışmaya dâhil edildi. Bulgular: Hastaların 10'unda (%4,6) ikincil bulgu tespit edilmiştir. Tespit edilen ikincil bulguların 4'ü (%40) kanser fenotipleriyle ilişkili genlerde iken 6'sı (%60) kardiyovasküler fenotipleriyle ilişkili genlerdeydi. Lynch sendromu, ailesel hiperkolesterolemi ve dilate kardiyomiyopati, hastalarda en sık tespit edilen ikincil bulgularla ilişkili hastalıklardı. Doğuştan gelen metabolizma hataları fenotipleriyle ilişkili genlerde ikincil bulgu tespit edilmedi. Sonuç: Bildiğimiz kadarıyla Türk toplumunda güncel ACMG tavsiyeleriyle WES verilerinden ikincil bulguları değerlendiren yayımlanmış bir çalışma yoktur. WES verilerinden morbidite ve mortaliteyi önlemeyi veya önemli ölçüde azaltmayı amaçlayan bilgileri çıkarmak, değerli ve hayat kurtarıcı bir çabadır. Bu çalışmanın sonuçları, ekzom dizilemede ikincil bulgular hakkında mevcut bilgilere ve Türk toplumunda gelecekteki çalışmalara katkı sağlayacaktır.

Anahtar Kelimeler: Tesadüfi bulgular; tüm ekzom sekanslama
ABSTRACT
 Objective: Whole exome sequencing (WES) is an effective molecular method used in the diagnosis of diseases that show genetic and clinical heterogeneity in their etiology. Also with this method, in addition to the primary disease that causes the patient to undergo genetic testing, variants in genes that cause life-threatening or preventable diseases, called secondary findings, can also be detected. The aim of this study is to investigate the frequency of secondary findings in patients undergoing WES. Material and Methods: The study is a retrospective study and WES datas of 216 (113 male, 103 female) patients were investigated for secondary findings according to American College of Medical Genetics and Genomics (ACMG) SF v3.2 recommendations. Pathogenic and likely pathogenic variants in relevant genes were included in the study. Results: Secondary findings were detected in 10 of the (4.6%) patients. Of the secondary findings detected, 4 (40%) were in genes related to cancer phenotypes and 6 (60%) were in genes related to cardiovascular phenotypes. Lynch syndrome, familial hypercholesterolemia and dilated cardiomyopathy were the most frequently detected diseases in patients. No secondary findings were detected in genes related with inborn errors of metabolism phenotypes. Conclusion: To our knowledge, there is no published study evaluating secondary findings from WES data with current ACMG recommendations in the Turkish population. Extracting information aimed at preventing or significantly reducing morbidity and mortality from WES data is a valuable and life-saving endeavor. The results of this study will contribute to the current knowledge about secondary findings in exome sequencing and future studies in the Turkish population.

Keywords: Incidental findings; whole exome sequencing
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