# Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report

## TL;DR

A young Ecuadorian child with heart rhythm issues was found to have a new genetic variant in the NKX2-5 gene, which may be linked to their condition.

## Contribution

A novel missense variant in NKX2-5 is identified in a mestizo patient with AV block and bradycardia, emphasizing the role of genomic and ancestral analysis in personalized diagnostics.

## Key findings

- A missense variant p.(Tyr274Ser) in NKX2-5 was identified in a young Ecuadorian patient with AV block and bradycardia.
- The patient's genetic background includes 16.5% African, 45.9% European, and 37.6% Native American ancestry.
- The variant is classified as a variant of uncertain significance (VUS), suggesting a potential link to the patient's cardiac phenotype.

## Abstract

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.