ASSESSMENT OF CHROMOSOMAL MICROARRAY FINDINGS IN THE MOLECULAR DIAGNOSIS OF CONGENITAL HEART DISEASES

Öz

Objective: Congenital heart disease (CHD) is one of the most frequently encountered congenital anomalies, resulting in significant mortality ratios. Early diagnosis of CHD is critical for effective disease management. Therefore, molecular approaches could provide valuable insights into the differential and early diagnosis of CHD. In the present study, we evaluated the efficiency and outcomes of the chromosomal microarray (CMA) method in patients with clinically diagnosed CHD. Material and Methods: The study included 113 patients with CHD from a single center in Türkiye. CMA was performed using the Agilent Technologies array comparative genomic hybridisation system. Variants were classified based on the guidelines of the American College of Medical Genetics and Genomics (ACMG). Results: Participants were classified as isolated (n=25) or syndromic CHD with additional conditions, including developmental delays, intellectual disabilities, growth retardation, other organ abnormalities, or dysmorphic features (n=88). CMA identified pathogenic copy number variants (CNVs) in 12 patients (10.6%). All patients with pathogenic CNVs belonged to the syndromic group (12/88; 13.6%). The most common CNVs were in the 22q11.2 region. Additionally, three CNVs identified in two patients had unique breakpoints that had not previously been reported. Conclusion: The current study substantiated the findings reported in the literature and demonstrated the diagnostic efficacy of CMA, particularly in cases of syndromic CHD. This study is expected to offer new insights into the current literature through additional clinical findings and previously unreported CNVs.

Anahtar Kelimeler

• Congenital heart disease
• chromosomal microarray
• copy number variation

KONJENİTAL KALP HASTALIĞININ MOLEKÜLER TANISINDA KROMOZOMAL MİKRODİZİN BULGULARININ DEĞERLENDİRİLMESİ

Öz

Amaç: Konjenital kalp hastalığı (KKH) yüksek mortalite oranlarıyla en sık karşılaşılan konjenital anomaliler arasındadır. Hastalığın etkin bir şekilde yönetimi için erken tanı kritiktir. Bu noktada, moleküler yaklaşımlar, KKH’nin erken ve ayırıcı tanısı için önem arz etmektedir. Bu çalışmada, klinik olarak KKH tanısı almış hastalarda kromozomal mikrodizin yönteminin sonuçları ve etkinliği değerlendirilmiştir Gereç ve Yöntemler: Çalışmaya Türkiye’den 113 KKH’li hasta dahil edilmiştir. Kromozomal mikrodizin, katılımcıların periferik kanından izole edilen genomik DNA ile Agilent Technologies platformu kullanılarak gerçekleştirilmiştir. İşlem sonunda varyantlar, Amerikan Tıbbi Genetik Derneği kriterleri doğrultusunda sınıflandırılmıştır. Bulgular: Katılımcılar, izole (n=25) ya da gelişme geriliği, bilişsel yetersizlik, büyüme geriliği, diğer organ anomalileri ya da dismorfik bulgular gibi ek özellikleri içeren sendromik KKH (n=88) olarak iki gruba ayrılmıştır. Kromozomal mikrodizin ile 12 hastada (%10,6) patojenik kopya sayısı değişimi (KSD) tespit edilmiştir. Bu hastaların tamamı, sendromik grupta yer almaktadır. En sık KSD, 22q11.2 bölgesinde görülmüştür. Sonuç: Bu çalışma, literatürde raporlanan sonuçları doğrulamış ve özellikle sendromik KKH vakalarında kromozomal mikrodizin yönteminin verimliliğini kanıtlamıştır. Bu çalışma, ek klinik bulgular ve daha önce bildirilmemiş CNV’lerin raporlanması ile literatüre katkı sağlamaktadır

Anahtar Kelimeler

• Konjenital kalp hastalığı
• Kromozomal mikrodizin
• Kopya sayısı varyasyonu

Kaynakça

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