Emerin and cardiomyopathy in Emery-Dreifuss muscular dystrophy.
Emery-Dreifuss muscular dystrophy (EDMD) is an inherited disorder characterized by the clinical triad of life-threatening progressive cardiomyopathy with conduction defect, early onset joint contractures and slow progressive muscle weakness in scapulo-humero-peroneal distribution. Cardiomyopathy in EDMD is usually noticed after the second to third decade of life, and becomes worse with age. Permanent auricular paralysis occurs frequently and is considered a hallmark of EDMD cardiomyopathy. Cardiac involvement may also occur in female carriers. In autopsy cases, enlargement of the atria with remarkable thinning have been observed. Identification of the gene responsible for X-linked EDMD (X-EDMD) and the protein product, emerin, provided a diagnostic clue for EDMD. Since the emerin gene is rather small, the entire sequence can easily be surveyed. Western blot and immunohistochemistry show an absence of emerin in muscle and skin tissues and oral exfoliating cells in male patients with X-EDMD, and a reduction of the protein content with a mosaic expression pattern in female carriers. Emerin anchors at the inner nuclear membrane of cardiac, skeletal and smooth muscles, and interacts with lamins and nucleoplasm, thereby possibly maintaining the mechanical stability of the nuclear membrane of muscle cells that shows rigorous contraction/relaxation. More recently, positive emerin staining at the cardiac demosomes and fasciae adherentes was noticed in addition to the specific localization at the inner nuclear membrane. This localization implies a physiological role for the protein in cardiac conduction.
Funakoshi
M
M
Department of Neuromuscular Research, National Institute of Neuroscience, Tokyo, Japan.
Tsuchiya
Y
Y
Arahata
K
K
D009202:Cardiomyopathies / Q000235:genetics*; D008040:Genetic Linkage; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D009136:Muscular Dystrophies / Q000235:genetics*; D020389:Muscular Dystrophy, Emery-Dreifuss; D009687:Nuclear Proteins; D013946:Thymopoietins / Q000235:genetics*; D014960:X Chromosome
D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin