Work

Homozygous LMNA (p.Arg216His) variant in an Ecuadorian patient with atrial flutter and high-grade atrioventricular block: a case report

Year: 2026

Type: article

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.

Source: Frontiers in Cardiovascular Medicine

DOI: 10.3389/fcvm.2026.1967331