Emery–Dreifuss muscular dystrophy

The Emery -Dreifuss muscular dystrophy ( EDMD ) in 1962 first described as a distinct muscular dystrophy. There are currently two known hereditary forms of the disease. First, it can occur (X -linked EDMD ) by the mutation of the 34 -kDa core protein emerin ( locus Xq28 ). Furthermore, various mutations in the LMNA gene ( locus 1q21 ), which encodes the core structural proteins lamin A / C, the autosomal dominant form of the disease initiate (AD- EDMD ).

Symptoms

The symptoms of the disease occur slowly in young patients in appearance. The disease can be characterized by three different abnormalities:

  • In most patients, a shortening of the Achilles tendon and muscle elbow is recognizable. For those affected, it is usually not possible durchzustrecken the arm or the leg.
  • In many patients, a slow wear and tear of the muscles with subsequently occurring muscle weakness is visible.
  • Advanced cardiac vessels, especially in the right atrium of the heart, are the result of the EDMD.

Diagnosis

For diagnosis of EDMD the first sign of a disease is to increase the serum levels of creatine kinase. Furthermore, electromyography can be applied for the detection of advanced cardiac components. The muskelhistologie usually shows muscle necrosis and phagocytosis of necrotic muscle cells.

Molecular Pathology

The gene locus for X -linked EDMD is XP28. The gene STA 2100 base pairs long and contains six exons. The result is a 34 kDa protein called Emerin, which is expressed in the inner nuclear membrane of skeletal, cardiac and smooth muscle. Mutation databases recorded so far several hundred mutations in the STA gene. All mutations in the STA gene result in a complete loss of emerin. The connection between the deletion of the core protein and the resulting muscular Emerin have so far not been elucidated.

The gene for the AD- EDMD was identified at the 1q21 locus. This gene encodes using the alternative Splicevorgangs the Kernlamine A and C, both of which are core structural proteins. They interact with chromatin, as well as with different IM proteins such as MAN1, emerin or LAPs. In addition to the AD- EDMD and the Limb- Gurtle dystrophy shows a mutation in the LMNA gene.

So far, the relationship between the mutation of the LMNA gene and the resulting muscular dystrophy was unclear and based only on speculation. Misteli et al. showed in a paper (2009) that a mislocalization of nuclei of muscle cells leads to an incorrect configuration of the motor endplate. For the positioning of the specialized cores at the motor endplate of the muscle cytoskeleton SUN proteins plays in connection with lamin A, Nesprin -1 and a major role. If one of these proteins is defective or not expressed, it comes to a mislocalization of synaptic nuclei at the postsynaptic neuromuscular junction. This means that the muscle can not be innervated correctly.

Therapy

Affected patients need to adapt their lifestyle. This includes the prevention of sports activities that can cause deformations in the muscle. Furthermore, the patients are treated with physiotherapy.

However, the most important aspect is the early detection of the disease in order to prevent heart defects can. Furthermore, it is useful to conduct a family history to identify possible genetic predisposition.

Some approaches that do not yet, however, are in clinical phase, deal with gene therapy and the use of adenoviral vectors for introduction of Emerinäquivalenten.

Swell

  • Méjat A et al.: Lamin A / C -mediated neuromuscular junction defects in Emery -Dreifuss muscular dystrophy. J Cell Biol 2009 January 12, 184 ( 1) :31- 44th Epub 2009 January 5, PMID 19124654
306567
de