Start with the gene and the protein network
LMNA encodes lamins A and C, proteins associated with the nuclear lamina, a network beneath the inner nuclear membrane. Laminopathies include diseases linked to alterations of these proteins. To understand a particular disorder, distinguish its human genetic evidence from experiments that remove lamin A/C altogether. [1] [3]
Human genetics: muscular dystrophy
Bonne and colleagues found four LMNA variants that co-segregated with autosomal dominant Emery-Dreifuss muscular dystrophy in five families. The disorder involves muscle weakness and can involve cardiac conduction disease. The result connects defined variants to a human phenotype; it does not mean that every LMNA change causes this disorder or has the same cellular effect. [1]
Human genetics: progeria and RNA splicing
Eriksson and colleagues identified the same newly arisen LMNA substitution in 18 of 20 classical Hutchinson-Gilford progeria cases. Although the substitution preserves the encoded amino acid, it activates an abnormal RNA splice site, producing lamin A missing 50 amino acids. Patient fibroblast staining also showed nuclear-envelope abnormalities. HGPS has premature-ageing-like features; these findings do not establish that ordinary ageing is the same process. [2]
A mechanical test uses a different model
Lammerding and colleagues stretched mouse embryonic fibroblasts lacking lamin A/C and compared them with wild-type cells. The deficient nuclei deformed more, and the cells showed reduced viability under mechanical strain and altered responses of mechanically stimulated genes. This demonstrates consequences of deficiency in that model. A complete mouse knockout is not equivalent to a particular human disease variant, so mechanical weakness is not a universal explanation of laminopathies. [3]
Primary studies behind this guide
- Bonne et al. (1999), Nature Genetics 21:285–288. Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy. DOI: 10.1038/6799. Primary research.
- Eriksson et al. (2003), Nature 423:293–298. Recurrent de novo point mutations in lamin A cause Hutchinson–Gilford progeria syndrome. DOI: 10.1038/nature01629. Primary research.
- Lammerding et al. (2004), Journal of Clinical Investigation 113:370–378. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. DOI: 10.1172/JCI19670. Primary research.
Scientific text and the identity and fit of the cited studies were checked on 3 October 2026. This guide covers the experiments described here; it is not an exhaustive literature review. See the audit record for access limits and remaining work.