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Prevalent cardiac phenotype resulting in heart transplantation in a novel LMNA gene duplication
1Department of Neuroscience, University of Pisa, Via Roma 67, 56126 Pisa, Italy. leda.vol@virgilio.it
Insights
A novel lamin A/C gene (LMNA) duplication mutation causes varied muscular dystrophy and cardiac dysfunction phenotypes. Early recognition of this genetic mutation may slow disease progression.
Area of Science:
- Genetics
- Molecular Biology
- Cardiology
Background:
- Mutations in the lamin A/C gene (LMNA) are associated with diverse disorders including muscular dystrophies and cardiomyopathies.
- Phenotypic heterogeneity is common in laminopathies, complicating diagnosis and treatment.
Observation:
- A novel autosomal dominant LMNA gene duplication was identified in two related individuals.
- The proband presented with severe limb-girdle muscle disease and cardiac dysfunction requiring heart transplantation.
- Her son exhibited ventricular tachyarrhythmias but maintained preserved cardiac and skeletal muscle function.
Findings:
- This is the first reported instance of a duplication mutation in the LMNA gene.
- The distinct clinical presentations in the relatives suggest different stages of the same disease spectrum.
- The identified mutation highlights the diverse pathogenic mechanisms within LMNA-related disorders.
Implications:
- Early identification of this LMNA duplication may allow for timely therapeutic interventions.
- Understanding the genotype-phenotype correlation can guide clinical management and prognosis.
- This finding expands the spectrum of known LMNA mutations and their associated clinical manifestations.
Abstract:
Mutations in the lamin A/C gene (LMNA) are known to be involved in several diseases such as Emery-Dreifuss muscular dystrophy, limb-girdle muscular dystrophy type 1B and dilated cardiomyopathies with conduction disease, with considerable phenotype heterogeneity. Here we report on a novel autosomal dominant mutation in LMNA in two direct relatives presenting with different clinical phenotypes, characterized by severe life-threatening limb-girdle muscle involvement and cardiac dysfunction treated with heart transplantation in the proband, and by ventricular tachyarrhythmias with preserved cardiac and skeletal muscle function in her young son. To our knowledge, this is the first report of a duplication in the LMNA gene. The two phenotypes described could reflect different clinical stages of the same disease. We hypothesize that early recognition and initiation of therapeutic manoeuvres in the younger patient may retard the rate of progression of the cardiomyopathy.
