Noonan sendromu: PTPN11 patojenik varyantları olan bireylerde moleküler ve klinik bulgular

Abstract

Amaç: RASopatiler, çoğalma, farklılaşma ve hayatta kalma gibi hücresel işlevler için kritik olan, Ras/mitojenle aktifleştirilen protein kinaz (RAS/MAPK) yolu ile ilişkili genlerdeki patojenik varyantlardan kaynaklanan, bir dizi bozukluğu kapsar. RASopatilerin en yaygın şekli olan Noonan sendromu (NS), karakteristik yüz dismorfizmleri, konjenital kalp defektleri ve gelişimsel gecikmeler dahil olmak üzere sayısız klinik özellik ile ortaya çıkar. Klinik olarak tanınmasına rağmen, vakaların kayda değer bir yüzdesinde moleküler doğrulama hala belirsizliğini korumaktadır. Bu çalışmada PTPN11 gen mutasyonu bulunan NS tanısı alan altı hastanın klinik ve moleküler profillerini araştırmayı amaçladık. Gereç ve yöntem: Klinik değerlendirmelere göre tipik NS fenotipine sahip olduğu düşünülen altı hastada PTPN11 gen dizi analizi ve tam gen dizileme yöntemleri kullanılarak moleküler değerlendirme yapıldı. Bulgular: Hastalarda yapılan moleküler taramada PTPN11 geninde dört farklı patojenik varyant tespit edildi. Tamamı heterozigot olan bu varyantlar, belirlenen kriterlere göre patojenik olarak sınıflandırıldı. Sonuç: Bulgularımız NS'nin genetik yapısının anlaşılmasına katkıda bulunmakta ve tanıların doğrulanmasında moleküler analizin öneminin altını çizmektedir.

Keywords

• Noonan sendromu
• PTPN11
• patojenik varyant
• SHP2

Noonan syndrome: molecular and clinical findings in individuals with PTPN11 pathogenic variants

Abstract

Purpose: RASopathies encompass a spectrum of disorders resulting from pathogenic variants in genes associated with the Ras/mitogen-activated protein kinase (RAS/MAPK) pathway, critical for cellular functions like proliferation, differentiation and survival. Noonan syndrome (NS), the most prevalent form of RASopathies, presents with a myriad of clinical features including characteristic facial dysmorphisms, congenital heart defects, and developmental delays. Despite its clinical recognition, molecular confirmation remains elusive in a notable percentage of cases. In this study, we aimed to investigate the clinical and molecular profiles of six patients diagnosed with NS, focusing on the role of PTPN11 gene mutations. Materials and methods: Molecular evaluation was performed using PTPN11 gene sequence analysis and whole gene sequencing methods in six patients who were thought to have typical NS phenotypes based on clinical evaluations. Results: Molecular screening in patients identified four different pathogenic variants in the PTPN11 gene. These variants, all heterozygous, were classified as pathogenic according to established criteria. Conclusion: Our findings contribute to understanding the genetic landscape of NS and underscore the significance of molecular analysis in confirming diagnoses.

Keywords

• Noonan syndrome
• PTPN11
• pathogenic variant
• SHP2

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