Mutations in the gene LMNA cause a wide spectrum of diseases that are now referred to laminopathies, such as muscular dystrophies, cardiomyopathies, and progeroid syndromes.
Early diagnosis of LMNA-related muscular dystrophy provides an opportunity for cardiac surveillance, potentially leading to the prevention of cardiac mortality in children.
To date, these findings have been limited to a few muscular dystrophy and lipodystrophy LMNA mutations but seem shared with a distinct nuclear envelope disease, emerin-deficient muscular dystrophy.
Mutations in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and premature ageing syndromes.
While mutations in lamin A specific residues cause several diseases including lipodystrophy, progeria, muscular dystrophy, neuropathy, and cardiomyopathy, only three families with mutations in lamin C-specific residues are reported with cardiomyopathy, neuropathy, and muscular dystrophy so far.
This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA)-related muscular dystrophy (MD).
Finally, we discuss potential implications of this concept for defining the molecular disease mechanisms of lamin-linked diseases such as muscular dystrophy and premature aging syndromes.
These findings elaborate a potential treatment option for dilated cardiomyopathy and muscular dystrophy associated with LMNA mutation and supplement growing evidence linking impaired autophagy to human disease.
Using skin fibroblasts from laminopathy patients and lamin A/C-deficient mouse embryonic fibroblasts stably expressing a broad panel of laminopathic lamin A mutations, we found that several mutations associated with muscular dystrophy and dilated cardiomyopathy resulted in more deformable nuclei; in contrast, lamin mutants responsible for diseases without muscular phenotypes did not alter nuclear deformability.
The cross-referencing of these mutations in candidate genes for muscular dystrophy showed a homozygote mutation c.G674A in exon 4 of LMNA causing a protein change R225Q in an arginine conserved from human to Xenopus tropicalis and in lamin B1.
Mutations in the lamin A/C gene (LMNA) cause a diverse spectrum of diseases, the most common of which is dilated cardiomyopathy often with skeletal muscular dystrophy.
Interest in the nuclear lamins increased dramatically in recent years with the realization that mutations in LMNA, the gene encoding lamins A and C, cause a panoply of human diseases ("laminopathies"), including muscular dystrophy, cardiomyopathy, partial lipodystrophy, and progeroid syndromes.
LMNA mutations are responsible for a variety of genetic disorders, including muscular dystrophy, lipodystrophy, and certain progeroid syndromes, notably Hutchinson-Gilford Progeria.
BAF-1 is also required to maintain the integrity of specific body wall muscles in adult animals, directly implicating BAF in the mechanism of human muscular dystrophies (laminopathies) caused by mutations in the BAF-binding proteins emerin and lamin A.