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

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 ve...

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Main Authors: Viviana A. Ruiz-Pozo, Santiago Cadena-Ullauri, Elius Paz-Cruz, Rafael Tamayo-Trujillo, Patricia Guevara-Ramirez, Paul Onofre-Ruiz, Ana Karina Zambrano
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Cardiovascular Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fcvm.2025.1552423/full
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author Viviana A. Ruiz-Pozo
Santiago Cadena-Ullauri
Elius Paz-Cruz
Rafael Tamayo-Trujillo
Patricia Guevara-Ramirez
Paul Onofre-Ruiz
Ana Karina Zambrano
author_facet Viviana A. Ruiz-Pozo
Santiago Cadena-Ullauri
Elius Paz-Cruz
Rafael Tamayo-Trujillo
Patricia Guevara-Ramirez
Paul Onofre-Ruiz
Ana Karina Zambrano
author_sort Viviana A. Ruiz-Pozo
collection DOAJ
description 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.
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publisher Frontiers Media S.A.
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series Frontiers in Cardiovascular Medicine
spelling doaj-art-4a3d955b688749c69435e4c255b8d5542025-08-20T03:04:30ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-04-011210.3389/fcvm.2025.15524231552423Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case reportViviana A. Ruiz-Pozo0Santiago Cadena-Ullauri1Elius Paz-Cruz2Rafael Tamayo-Trujillo3Patricia Guevara-Ramirez4Paul Onofre-Ruiz5Ana Karina Zambrano6Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Quito, EcuadorUniversidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Quito, EcuadorUniversidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Quito, EcuadorUniversidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Quito, EcuadorUniversidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Quito, EcuadorUniversidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Quito, EcuadorUniversidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Quito, EcuadorCardiovascular 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.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1552423/fullcase reportcardiovascular diseasegeneticsgenomicshealthcare
spellingShingle Viviana A. Ruiz-Pozo
Santiago Cadena-Ullauri
Elius Paz-Cruz
Rafael Tamayo-Trujillo
Patricia Guevara-Ramirez
Paul Onofre-Ruiz
Ana Karina Zambrano
Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report
Frontiers in Cardiovascular Medicine
case report
cardiovascular disease
genetics
genomics
healthcare
title Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report
title_full Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report
title_fullStr Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report
title_full_unstemmed Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report
title_short Identification of a novel NKX2-5 variant in a young Ecuadorian patient with atrioventricular block and bradycardia: a case report
title_sort identification of a novel nkx2 5 variant in a young ecuadorian patient with atrioventricular block and bradycardia a case report
topic case report
cardiovascular disease
genetics
genomics
healthcare
url https://www.frontiersin.org/articles/10.3389/fcvm.2025.1552423/full
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