Homozygous LMNA (p.Arg216His) variant in an Ecuadorian patient with atrial flutter and high-grade atrioventricular block: a case report.
5 affiliations
- 1Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Centro de Investigación Genética y Genómica, Quito, Ecuador.
- 2Clinical Cardiac Electrophysiologist, Quito, Ecuador.
- 3Universidad UTE, Facultad de Ciencias de la Salud Eugenio Espejo, Quito, Ecuador.
- 4Grupo de Bio-Quimioinformática, Universidad de Las Américas, Quito, Ecuador.
- 5Carrera de Enfermería, Facultad de Ciencias de la Salud, Universidad de Las Américas, Quito, Ecuador.
Abstract
Cardiac laminopathies caused by LMNA variants may present with conduction disease, atrial arrhythmias, and ventricular dysfunction, sometimes before overt ventricular dilation. We report a 42-year-old Ecuadorian man with recurrent syncope and progressive exertional dyspnea who developed atrial flutter with a markedly slow ventricular response, high-grade atrioventricular block, and severe bradycardia. Next-generation sequencing using the TruSight Cardio panel identified NM_170707.4(LMNA):c.647G > A (p.Arg216His) in a homozygous state. Franklin by QIAGEN classified the variant as pathogenic under the ACMG/AMP framework, although ClinVar contains conflicting interpretations and variant-specific functional and segregation studies were unavailable. Genetic ancestry analysis showed 89% Native American, 8.5% European, and 2.5% African ancestry. To our knowledge, p.Arg216His has not previously been reported in the homozygous state, whereas prior cardiac reports have involved heterozygous or compound heterozygous carriers, highlighting the novelty of this case report. This case expands the clinical and genotypic spectrum associated with LMNA-related cardiac disease and highlights the value of integrating electrophysiological, imaging, genomic, and ancestry data in underrepresented populations.
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BibTeX
@article{cadenaullauri2026homozygous,
title = {{Homozygous LMNA (p.Arg216His) variant in an Ecuadorian patient with atrial flutter and high-grade atrioventricular block: a case report.}},
author = {Santiago Cadena-Ullauri and Viviana A Ruiz-Pozo and Rafael Tamayo-Trujillo and Patricia Guevara-Ramírez and Elius Paz-Cruz and Rita Ibarra-Castillo and José Luis Laso-Bayas and Paul Onofre-Ruiz and Alejandro Cabrera-Andrade and Ana Karina Zambrano},
journal = {Frontiers in cardiovascular medicine},
year = {2026},
month = oct,
doi = {10.3389/fcvm.2026.1967331},
url = {https://europepmc.org/article/MED/42908657},
note = {CC BY},
}
RIS
TY - JOUR
TI - Homozygous LMNA (p.Arg216His) variant in an Ecuadorian patient with atrial flutter and high-grade atrioventricular block: a case report.
AU - Santiago Cadena-Ullauri
AU - Viviana A Ruiz-Pozo
AU - Rafael Tamayo-Trujillo
AU - Patricia Guevara-Ramírez
AU - Elius Paz-Cruz
AU - Rita Ibarra-Castillo
AU - José Luis Laso-Bayas
AU - Paul Onofre-Ruiz
AU - Alejandro Cabrera-Andrade
AU - Ana Karina Zambrano
PY - 2026
DA - 2026/10/07
JO - Frontiers in cardiovascular medicine
DO - 10.3389/fcvm.2026.1967331
UR - https://europepmc.org/article/MED/42908657
AB - Cardiac laminopathies caused by LMNA variants may present with conduction disease, atrial arrhythmias, and ventricular dysfunction, sometimes before overt ventricular dilation. We report a 42-year-old Ecuadorian man with recurrent syncope and progressive exertional dyspnea who developed atrial flutter with a markedly slow ventricular response, high-grade atrioventricular block, and severe bradycardia. Next-generation sequencing using the TruSight Cardio panel identified NM_170707.4(LMNA):c.647G > A (p.Arg216His) in a homozygous state. Franklin by QIAGEN classified the variant as pathogenic under the ACMG/AMP framework, although ClinVar contains conflicting interpretations and variant-specific functional and segregation studies were unavailable. Genetic ancestry analysis showed 89% Native American, 8.5% European, and 2.5% African ancestry. To our knowledge, p.Arg216His has not previously been reported in the homozygous state, whereas prior cardiac reports have involved heterozygous or compound heterozygous carriers, highlighting the novelty of this case report. This case expands the clinical and genotypic spectrum associated with LMNA-related cardiac disease and highlights the value of integrating electrophysiological, imaging, genomic, and ancestry data in underrepresented populations.
SN - 2297-055X
ER -