In Reply We welcome the letter by Castrichini et al highlighting their concerns about the inclusion of patients with familial lipodystrophy type 2 (FPLD2) in our recent article describing the cardiac outcomes of patients with LMNA variants. We agree that the results of prior preclinical and observational studies suggest an alternative pathomechanistic pathway for patients with p.Arg482 hotspot variants compared with other LMNA variants.
Inclusion of this cohort in our study was to further interrogate these findings and appreciate the full spectrum of cardiac disease with LMNA variants. While there were no primary outcome events in this subgroup, 4 patients with missense variants affecting the p.Arg482 hotspot did experience advanced heart failure events, highlighting its relevance for overall cardiac outcomes.
JAMA Cardiology published a clinical update in Cardiology on 01 Apr 2026.
The item focuses on Location of LMNA Variants and Clinical Outcomes in Cardiomyopathy—Reply.
Review the original article for the full source wording and details.