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Epidemiological data on Steinert desease - Different forms of myotonic dystrophy - Transmission of myotonic dystrophy - Signs of myotonic dystrophy 

ResponsIble genes - How is myotonic dystrophy diagnosed - Risks of myotonic dystrophy - Treatment of myotonic dystrophy

 

   There are currently 3 forms of Myotonic Dystrophy: Type 1 Myotonic Dystrophy (Steinert Disease), Type 2 Myotonic Dystrophy and Type 3 Myotonic Dystrophy. Each form is caused by mutations in different genes.

The gene for Type 1 Myotonic Dystrophy or Steinert Disease

    The genetic anomaly responsible for Type 1 Myotonic Dystrophy was identified in 1992. It is located on chromosome 19, a chromosome that is not implicated in the determination of the sex of the individual. This gene was identified as the gene for myotonin-protein kinase. This name comes from the fact that the gene carries the information to produce an enzyme that is part of the protein kinase family.

    Each gene is made up of three parts. The  promoting area (blue) is responsible for gene expression in tissues as well as gene regulation. This means that this area will make it possible for gene to be expressed in the muscle but not in the brain, for example. This area also controls the level of expression of the gene which determines whether it can be activated or inhibited depending on its environment. The second area holds the information for protein production (green) and the third area at the extremity of the gene (grey) plays a little known role. The genetic anomaly responsible for Myotonic Dystrophy is located in this third area.

 

 

Figure 2: The gene for Type 1 Myotonic Dystrophy. The gene contains an area that is responsible for its expression and regulation (blue), an area containing the information for protein synthesis (green) and a non coding 3’ area whose role is not well known (grey).

To understand the genetic anomaly, we must go over gene composition. Genes can be compared to the letters of the alphabet i.e. they are composed of letters. The gene alphabet has 4 letters A, T, C, G that are repeated in varying order. These letters are used to form words. In genetics, all words are composed of 3 letters (for example: ATC). In Myotonic Dystrophy, the word is CTG. In the normal population, this word is repeated several times within the Myotonic Dystrophy gene but always less than 40 times (CTG-CTG-CTG-CTG-etc.). For reasons still unknown, the number of repetitions can be up to 3000 to 5000 times. This is the anomaly responsible for Type 1 Myotonic Dystrophy.

The gene for Type 2 Myotonic Dystrophy

    The genetic anomaly responsible for Type 2 Myotonic Dystrophy is located in a gene that is located on chromosome 3 that codes for a protein called: ZNF9. In order to understand the localisation of the genetic anomaly, here is a brief reminder on gene structure. As mentioned in the previous paragraph, genes are made of 4 letters that are repeated in varying order. Genes have portions that contain information for the synthesis of proteins (these portions are called exons) and portions that contain no information for the synthesis of proteins (these portions are called introns). Genes are located in the nucleus of the cells and the specific information for synthesis of a specific protein must be transmitted to the protein production site that is located within the body of the cell. The transporter of this information is called the RNA messenger (mRNA).

 

Figure 3: Structure of a maturing gene. The represented gene is comprised of 4 exons (yellow) and 3 introns (green). It is first transformed into an RNA precursor that contains the exons and introns. Secondly, the introns are eliminated and the exons link together to form the RNA messenger (mRNA) that will bring the information contained in the gene to the protein production site that is located in the cytoplasm.

Transmission of the information contained in a gene and brought to the protein production site happens as follows:

  • The information is transmitted from the gene to the precursor of the transporter in the nucleus. The transporter contains all the parts of the gene, excluding the exons and introns.

  • In the next phase, the transporter eliminates the introns within the nucleus and becomes the messenger (mRNA). This phenomenon is called splicing.

  • The mRNA leaves the nucleus and brings the information to the protein production site.

  • A protein is then produced.

Figure 4: The gene responsible for Type 2 Myotonic Dystrophy is transformed into an RNA precursor and then into an mRNA but the Intron-1's that contain the genetic anomaly will accumulate in the nucleus.

The genetic anomaly responsible for Type 2 Myotonic Dystrophy is a repetition of the word CCTG located in an intron, i.e. in a part of the gene that does not contain the information to produce a protein. This intron that contains the genetic anomaly accumulates in the nucleus of the cells.

The gene for Type 3 Myotonic Dystrophy

    The gene responsible for Type 3 Myotonic Dystrophy has not yet been identified. Gene linkage studies seem to indicate that the gene is located on chromosome 16. A study published in 2004 led us to believe that the DM3 found in a French family was located on chromosome 15 but these results were not confirmed.

Human genetic department

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E-mail: sec.genetique@crchul.ulaval.ca

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