Novel pathogenic variant in LMNA gene identified in a six-generation family causing atrial cardiomyopathy and associated right atrial conduction arrhythmias

Objective To characterize the cardiac phenotype associated with novel pathogenic variant (c.1526del) of LMNA gene, which we identified in a large, six-generation family. Methods and Results A family tree was constructed. The clinical data living deceased members were collected. DNA samples from 7 analyzed for mutations using whole-exome high-throughput sequencing technology. presentation carriers evaluated. In this ( n = 67), one member experienced sudden death at age 40-years-old. Three to possess heterozygous deletion mutation gene (HGVS: NM_170707.4, c.1526del) located exon 9 chr1:156137145, creates premature translational stop signal (p.Pro509Leufs*39) results an mutant lamin protein product. main symptoms palpitation, fatigue, syncope, typically occurred around 20-years-old. AV-conduction block non-sustained ventricular tachycardia first signs disease would rapidly progress atrial standstill 30-years-old. Significant right enlargement bicuspid aortic valve malformation also commonly seen patients who carried variant. Conclusion c.1526del p.P509Lfs*39 frameshift chr1:156137145 causes severe enlargement, sick sinus syndrome, standstill, tachycardia, malformation. Our findings expand phenotypic spectrum mutations.