Biomedicines (Jun 2024)

Missense and Non-Missense Lamin A/C Gene Mutations Are Similarly Associated with Major Arrhythmic Cardiac Events: A 20-Year Single-Centre Experience

  • Cinzia Forleo,
  • Maria Cristina Carella,
  • Paolo Basile,
  • Eugenio Carulli,
  • Michele Luca Dadamo,
  • Francesca Amati,
  • Francesco Loizzi,
  • Sandro Sorrentino,
  • Ilaria Dentamaro,
  • Marco Maria Dicorato,
  • Stefano Ricci,
  • Rosanna Bagnulo,
  • Matteo Iacoviello,
  • Vincenzo Ezio Santobuono,
  • Carlo Caiati,
  • Martino Pepe,
  • Jean-Francois Desaphy,
  • Marco Matteo Ciccone,
  • Nicoletta Resta,
  • Andrea Igoren Guaricci

DOI
https://doi.org/10.3390/biomedicines12061293
Journal volume & issue
Vol. 12, no. 6
p. 1293

Abstract

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Arrhythmic risk stratification in patients with Lamin A/C gene (LMNA)-related cardiomyopathy influences clinical decisions. An implantable cardioverter defibrillator (ICD) should be considered in patients with an estimated 5-year risk of malignant ventricular arrhythmia (MVA) of ≥10%. The risk prediction score for MVA includes non-missense LMNA mutations, despite their role as an established risk factor for sudden cardiac death (SCD) has been questioned in several studies. The purpose of this study is to investigate cardiac features and find gene–phenotype correlations that would contribute to the evidence on the prognostic implications of non-missense vs. missense mutations in a cohort of LMNA mutant patients. An observational, prospective study was conducted in which 54 patients positive for a Lamin A/C mutation were enrolled, and 20 probands (37%) were included. The median age at first clinical manifestation was 41 (IQR 19) years. The median follow-up was 8 years (IQR 8). The type of LMNA gene mutation was distributed as follows: missense in 26 patients (48%), non-frameshift insertions in 16 (30%), frameshift deletions in 5 (9%), and nonsense in 7 (13%). Among the missense mutation carriers, two (8%) died and four (15%) were admitted onto the heart transplant list or underwent transplantation, with a major adverse cardiovascular event (MACE) rate of 35%. No statistically significant differences in MACE prevalence were identified according to the missense and non-missense mutation groups (p value = 0.847). Our data shift the spotlight on this considerable topic and could suggest that some missense mutations may deserve attention regarding SCD risk stratification in real-world clinical settings.

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