Myotonic dystrophy; Myotonic dystrophy type 1; Steinert disease (Myotonic dystrophy type 1) - Gen DMPK

The myotonic dystrophy, is part of a group of inherited diseases called muscular dystrophies. This form is the most common muscular dystrophies start in adulthood (20 to 30 years), but may also occur at other ages. It is characterized by progressive muscle weakness and weight loss. Affected individuals often manifest muscle contractions (myotonia), and can not relax certain muscles after movement. Sometimes they may have mandibular block. Other signs and symptoms include lens opacification (cataract), and abnormal electrical signals cardiac conduction. In males may be hormonal changes that cause infertility.

There are two types of myotonic dystrophies, the type 1 (Steinert disease) and type 2. Signs and symptoms of both overlap. In type 1 (Steinert), muscle weakness affects the muscles of the legs, hands, neck and face. In type 2 it is most affects the neck, shoulders, elbows and hips. In addition, Type 2 is milder than type 1. Moreover, the affected genes are different in both types, DMPK gene in type 1, and CNBP gene in type 2 - see myotonic dystrophy type 2 -.

A mutation in the DMPK gene (dystrophia Myotonic Protein Kinase gene), located on the long arm of chromosome 19 (19q13.3), is responsible for muscular dystrophy type 1 (Steinert). This gene encodes protein kinase myotonic dystrophy. Although the specific function of this protein is unknown, it seems to play an important role in muscle cells, heart and brain. This protein may be involved in communication in the inside cells. Also it appears to regulate the production and function of the important structures inside the muscle cells by interacting with other proteins. For example, it has been shown to inhibit myosin phosphatase of muscle protein. Myosin phosphatase is an enzyme that plays a role in muscle contraction and relaxation. A region of DMPK gene contains a segment triblock nucleotide are repeated several times. This repeated sequence, in this case CTG, is called a triplet or trinucleotide repeats. In most people, the number of CTG repeats in this gene is 5 to 34. The mutation results in myotonic dystrophy is an expansion of trinucleotide repeats located at the 3'end. This mutation increases the size CTG segment, where there may be up to 50 CTG triplet. The number of repetitions may be even greater in certain cell types, such as muscle cells. These repeats result in an unstable region in the gene, which produces an expanded version of the messenger RNA. This messenger, abnormally long, RNA is grouped within the cell and interferes with the synthesis of other cellular proteins. The normal protein encoded by this participates in intercellular communication, so alteration also cause an alteration of the functional status of muscle cells, and other cells of other tissues, leading to the signs and symptoms of this disease.

The disease shows autosomal dominant, so the altered copy of the gene in each cell causes disease. In most cases, those affected have a parent with the disease, and the disease is transmitted from one generation to the next.

Tests in IVAMI: in IVAMI perform the complete PCR amplification followed by sequencing of the DMPK gene in its 3'detecting triplets of repeated nucleotides.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).