Identification of a Novel NKX2-5 Variant in a Young Ecuadorian Patient with Atrioventricular Block and Bradycardia: a case report

Viviana A. Ruiz-Pozo Santiago Cadena-Ullauri Elius Andrés Paz Cruz Rafael Tamayo-Trujillo Patricia Guevara-Ramirez Mateo Antonio Rodríguez Ana Karina Zambrano ^*

• Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica., Quito, Ecuador

Cardiovascular diseases (CVDs) are the leading global cause of mortality, with South America reflecting similar trends. Among congenital heart diseases (CHDs), atrioventricular (AV) block is included. AV block is a condition defined by abnormal electrical signal transmission between the atria and ventricles. Advances in Next-Generation Sequencing (NGS) have facilitated the identification of genetic variants associated with cardiac disorders, such as AV block. Notably, the transcription factor NKX2-5 plays a crucial role in heart development and function, and mutations in this gene have been linked to bradycardia and AV block. This article describes the case report of a young Ecuadorian child diagnosed with AV block and bradycardia. Furthermore, by performing NGS, a missense variant, p.(Tyr274Ser) substitution, in the NKX2-5 gene has been identified and classified as a variant of uncertain significance (VUS). Ancestral analysis has shown a genetic background of 16.5% African, 45.9% European, and 37.6% Native American. These findings suggest a potential association between the identified NKX2-5 variant and the patient's phenotype, highlighting the importance of integrating genomic and ancestral analyses to advance personalized diagnostics and therapeutics in diverse populations, such as the mestizo population.