Kalıtsal trombositopeni hastalarının hedeflenmiş yeni nesil dizi analizi sonuçlarının retrospektif olarak değerlendirilmesi
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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
Kalıtsal trombositopeniler, trombosit sayısının düşük olması ile karakterize, kanama eğilimi oluşturan heterojen hastalık grubudur. Bu hastalık grubunda 2010 yılına kadar 36 farklı form tanımlanmıştır. Genetik teknolojilerdeki gelişmeyle birlikte günümüzde en az 51 farklı hastalığın bu tabloya sebep olduğu bilinmektedir. Her bir hastalığın tedavisi ve prognozu birbirinden farklıdır. Trombositopeni ile takip edilen olgularda önemli sorunlardan bir tanesi yanlış tanı ile takip edilme oranının yüksek olmasıdır. Yanlış tanı beraberinde yanlış medikal tedavi ve cerrahi girişimleri getirmektedir. Genetik testler olguları doğru tanıya bir adım daha yaklaştırmaktadır. Bu çalışmada, trombositopeni ön tanısı ile tarafımıza yönlendirilen 36 olgunun hedefe yönelik yeni nesil dizi analizi sonuçlarının retrospektif olarak değerlendirilmesi amaçlanmıştır. Çalışmaya alınan 36 olgunun 10'unda, kalıtsal trombositopeniye sebep olan genetik mutasyon mevcuttu. MYH9 geninde iki tanımlı (p.S96L, p.R702C), WAS geninde bir tanımlı (p.D485N), MPL geninde iki tanımlı (c.212+5G>A, p.L79EfsX84), GP1BA geninde bir tanımlı (p.N150S) ve NBEAL2 geninde iki yeni (c.7878+2G>A, p.G2520V) mutasyon saptanmıştır. Olguların klinik ve genetik özellikleri, genotip-fenotip korelasyonu açısından ele alındı. Bu çalışma, kalıtsal trombositopeni hasta grubundaki mutasyon dağılımını inceleyen ülkemizdeki az sayıdaki çalışmadan biridir. Moleküler genetik çalışmaların olgulardaki klinik yaklaşıma etkisi değerlendirildi. Bu olgu grubunda moleküler tanı konulması, hastalara tedavi ve prognoz tahmini açısından önemli katkılar sunmakla birlikte preimplantasyon genetik tanı yoluyla sağlıkla kuşakların oluşmasına katkıda bulunacaktır.
Inherited thrombocytopenias are a heterogeneous group of diseases that are characterized by low platelet count which causes bleeding tendency. Until 2010, 36 different forms were defined in this disease group. Today, through to advances in genetic technologies, at least 51 different diseases are known to cause this condition. The treatment and prognosis of each disease are different. As a result of the high rate of misdiagnosis, these cases undergo inappropriate treatment and surgical procedures. Genetic tests contribute to the correct diagnosis in these cases. In this study, we aimed to retrospectively evaluate the results of targeted next generation sequencing analysis of 36 patients who were referred with the initial diagnosis of thrombocytopenia retrospectively. In the 10 of the 36 cases included in the study had a genetic mutation causing inherited thrombocytopenia. Mutations in the cases were as follows: Two previously reported (p.S96L, p.R702C) in MYH9 gene, one previously reported (p.D485N) in WAS gene, two previously reported (c.212+5G>A, p.L79EfsX84) in MPL gene, one previously reported (p.N150S) in GP1BA gene and two novel mutation (c.7878+2G>A, p.G2520V) in NBEAL2 gene. The clinical and genetic characteristics of the cases were discussed in terms of genotype phenotype correlation. This study is one of the few studies in our country to showing distribution of mutations in inherited thrombocytopenia patient group. We evaluated the molecular genetic studies effect on the clinical approach these cases. Molecular genetic diagnosis provides important contributions for patients both in terms of treatment-prognosis prediction and growing of a healthy generation via preimplantation genetic diagnosis.
Inherited thrombocytopenias are a heterogeneous group of diseases that are characterized by low platelet count which causes bleeding tendency. Until 2010, 36 different forms were defined in this disease group. Today, through to advances in genetic technologies, at least 51 different diseases are known to cause this condition. The treatment and prognosis of each disease are different. As a result of the high rate of misdiagnosis, these cases undergo inappropriate treatment and surgical procedures. Genetic tests contribute to the correct diagnosis in these cases. In this study, we aimed to retrospectively evaluate the results of targeted next generation sequencing analysis of 36 patients who were referred with the initial diagnosis of thrombocytopenia retrospectively. In the 10 of the 36 cases included in the study had a genetic mutation causing inherited thrombocytopenia. Mutations in the cases were as follows: Two previously reported (p.S96L, p.R702C) in MYH9 gene, one previously reported (p.D485N) in WAS gene, two previously reported (c.212+5G>A, p.L79EfsX84) in MPL gene, one previously reported (p.N150S) in GP1BA gene and two novel mutation (c.7878+2G>A, p.G2520V) in NBEAL2 gene. The clinical and genetic characteristics of the cases were discussed in terms of genotype phenotype correlation. This study is one of the few studies in our country to showing distribution of mutations in inherited thrombocytopenia patient group. We evaluated the molecular genetic studies effect on the clinical approach these cases. Molecular genetic diagnosis provides important contributions for patients both in terms of treatment-prognosis prediction and growing of a healthy generation via preimplantation genetic diagnosis.
Açıklama
Anahtar Kelimeler
Kalıtsal Trombositopeni, Yeni Nesil Dizi Analizi, Genotip-Fenotip Korelasyonu, Inherited Thrombocytopenia, Next-Generation Sequencing, Genotype- Phenotype Correlation
