LMNA
Lamin A/C
Gene Summary
RefSeq / NCBIThe protein encoded by this gene is part of the nuclear lamina, a two-dimensional matrix of proteins located next to the inner nuclear membrane. The lamin family of proteins make up the matrix and are highly conserved in evolution. During mitosis, the lamina matrix is reversibly disassembled as the lamin proteins are phosphorylated. Lamin proteins are thought to be involved in nuclear stability, chromatin structure and gene expression. Vertebrate lamins consist of two types, A and B. Alternative splicing results in multiple transcript variants. Mutations in this gene lead to several diseases: Emery-Dreifuss muscular dystrophy, familial partial lipodystrophy, limb girdle muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease, and Hutchinson-Gilford progeria syndrome. [provided by RefSeq, May 2022]
Clinical Phenotype
Multiple allelic diseases: Emery-Dreifuss muscular dystrophy (EDMD2), LGMD1B, dilated cardiomyopathy with conduction defect, Dunnigan partial lipodystrophy, and Hutchinson-Gilford progeria. Cardiac involvement in EDMD2 is severe and life-threatening.
Molecular Mechanism
Lamin A/C are type V intermediate filaments of the nuclear lamina, providing structural support to the nucleus and organizing chromatin. Mutations disrupt nuclear integrity, mechanosensing, and gene regulation, particularly in mechanically stressed tissues (cardiac and skeletal muscle).
Clinical Hallmarks & Key Evidence
The EDMD clinical triad: (1) early joint contractures (elbows, Achilles), (2) slowly progressive humeroperoneal weakness, (3) cardiac arrhythmia and dilated cardiomyopathy.
Emery AE, Dreifuss FE. J Neurol Neurosurg Psychiatry. 1966;29(4):338-42.
Cardiac arrhythmia in LMNA disease may predate muscle weakness; sudden cardiac death has occurred in teenage athletes — ICD implantation guidelines are stricter than for other cardiomyopathies.
van Rijsingen IA et al. J Am Coll Cardiol. 2012;59(6):493-500.
LMNA mutations cause ~5–10% of all familial dilated cardiomyopathy; genetic testing is recommended for DCM with conduction disease even in the absence of muscle involvement.
Parks SB et al. Heart Rhythm. 2008;5(3):440-45.
External Resources
Gene data compiled from the Washington University Neuromuscular Disease Center, NCBI Gene, and OMIM. For clinical use, always refer to primary sources.