Türk Kardiyomiyopati Hastalarında Hipertrofik Kardiyomiyopati ile İlişkili Gen Paneli Kullanılarak Genotip ve Fenotip Analizi Yapılması

Giriş ve Amaç: Hipertrofik kardiyomiyopati (HCM), sarkomerik proteinlerdeki mutasyonların neden olduğu ve kalp kasının hipertrofisi ile karakterize otozomal dominant bir hastalıktır. Gereç ve Yöntemler: Bu çalışmada, 21 HCM hastası ve bazılarının ebeveynleri, 17 genden oluşan hedeflenmiş bir panel kullanılarak yeni nesil dizileme aracılığıyla değerlendirilmiştir. Bulgular: 6 hastada, MYH7 (p.R663C, p.A423V), MYBPC3 (p.P955fs*95, p.K301fs*31), TNNT2 (p.R154Q) ve TNNI3 (p.R204C) genlerinde patojenik veya yüksek olasılıkla patojenik varyantlar tespit edilmiştir. Sonuç: Klinik bulgular literatür ile karşılaştırılarak bu varyantların genotip-fenotip korelasyonları tartışıldı. TNNI3 genindeki p.R204C varyantının literatürde ilk kez restriktif kardiyomiyopatiye neden olduğu saptanmıştır

Anahtar Kelimeler:

Hipertrofik kardiyomiyopati, MYH7, MYBPC3, TNNT2, TNNI3

Genotype and Phenotype Analysis Using a Hypertrophic Cardiomyopathy-Associated Gene Panel in Turkish Cardiomyopathy Patients

Objective: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in sarcomeric proteins and characterized by hypertrophy of the heart muscle. Materials and Methods: In the present study, 21 patients with HCM and some of their parents were evaluated via next-generation sequencing (NGS) using a targeted panel of 17 genes. Results: Pathogenic or likely pathogenic variants were detected in six patients in the genes MYH7 (p.R663C, p.A423V), MYBPC3 (p.P955fs*95, p.K301fs*31), TNNT2 (p.R154Q), and TNNI3 (p.R204C). Conclusion: The genotype-phenotype correlations of these variants were discussed by comparing the clinical findings with the literature. p.R204C variant in the TNNI3 gene was found to be caused restrictive cardiomyopathy for the first time in the literature.

Keywords:

Hypertrophic cardiomyopathy, MYH7, MYBPC3, TNNT2, TNNI3,

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