Lamin A C Gene Mutation

Lamins a and c are intermediate filament nuclear envelope proteins encoded by the lmna gene.

Lamin a c gene mutation. The nuclear lamina is thought to regulate gene expression by its direct interaction with chromatin. Lamin a c gene mutation associated with dilated cardiomyopathy with variable skeletal muscle involvement gary l. Laminopathies are caused among other mutations to mutations in lmna a gene that synthetizes lamins a and c. Characterised by progressive conduction system disease arrhythmia and systolic impairment lamin a c heart disease is more malignant than other common dcms due to high event rates even.

The lamin a c gene encodes 2 proteins that are members of the intermediate filament class of cytoskeletal proteins. Dominant lmnagene mutations cause multiple human diseases including cardiac and skeletal myopathies. Lamin a c congenital muscular dystrophy cmd l cmd congenital muscular dystrophy associated to the lmna gene or emery dreifuss muscular dystrophy ii is a disease that it is included in laminopathies. Mutations in the lamin a c gene can affect the heart skeletal muscles adipose tissues bones and nervous tissues with most cases resulting in dilated cardiomyopathy conduction defects dysrrhythmias and premature death.

Lamin a c mutations are a well established cause of dilated cardiomyopathy dcm although their frequency has not been examined in a large cohort of patients we sought to examine the frequency of mutations in lmna the gene encoding lamin a c in patients with idiopathic idc or familial dilated cardiomyopathy fdc. In embryonic cells upregulation of lamin a disturbs lamin c which may influence gene expression. The nt 959 deletion is predicted to result in a mutant protein that shares its 318 amino acid n terminal sequence with that of lamins a and c. Lamin a c mutations identified in individuals with isolated cardiac disease are predominantly found in the rod domain although no clear genotype phenotype relationship exists 9 14the majority of the currently identified predominantly cardiac disease causing mutations are missense mutations and surprisingly only a few are nonsense or frameshift mutations that result in premature lamin termination 15 16it is not clear whether the truncated lamins cause disease primarily by haploinsufficiency or by exerting dominant negative effects.

Mutations in the lmna gene are associated with several diseases including emery dreifuss muscular dystrophy familial partial lipodystrophy limb girdle muscular dystrophy dilated cardiomyopathy charcot marie tooth disease and restrictive dermopathy. Lamins a and c encoded by the lmnagene are filamentous proteins that form the core scaffold of the nuclear lamina.