Duchenne muscular dystrophy and Becker (Duchenne and Becker muscular dystrophy) - Gen DMD
The muscular dystrophies are genetic diseases group, characterized by progressive muscle weakness and atrophy. The Duchenne muscular dystrophy (DMD: Duchenne muscular dystrophy) and Becker muscular dystrophy (BMD: Becker muscular dystrophy), share symptoms and signs, and are caused by different mutations of the same DMD gene (dystrophin) encoding muscle protein "dystrophin"; but differ from them in severity, the age of onset and progression.
Duchenne muscular dystrophy is a rapidly progressive form of muscular dystrophy that occurs mainly in children. Affected children are delayed in their motor development as sitting, standing and walking, with a progressive loss of muscle function and weakness that starts in the lower extremities skills. This process is more common in men than in women. Signs and symptoms of Becker muscular dystrophy are milder and highly variable. In most cases they are become apparent in late childhood or adolescence, and progresses more slowly. In addition to affecting skeletal muscles can also affect the heart muscle, causing dilated cardiomyopathy with heart weakness that prevents adequate blood pumping. Signs and symptoms of dilated cardiomyopathy may include arrhythmia, shortness of breath, fatigue, and swelling of the legs and feet. These heart problems worsen quickly and in many cases can be potentially fatal. Boys with Duchenne muscular dystrophy usually live up to twenty years while men with Becker muscular dystrophy can survive beyond 40 years old.
A related condition called DMD dilated cardiomyopathy associated with a form of heart disease due to mutations in the same gene as the Duchenne muscular dystrophy and Becker, sometimes classified as Becker muscular dystrophy subclinical. People with dilated cardiomyopathy associated with DMD often have no skeletal muscle weakness or emaciation, although they may have subtle changes in skeletal muscle cells that are detectable by laboratory tests.
Dystrophin protein encoded by the DMD (dystrophin) gene located on the short arm of chromosome X (Xp21.2), stabilizes and protects the muscle fibers. This protein is found primarily in skeletal muscle and cardiac muscle. In addition, this protein is present in small quantities in brain neurons. In skeletal and cardiac muscle, dystrophin is part of a complex of proteins that act together to strengthen the muscle fibers and protect them from injury during muscle contraction and relaxation. Although little is known about the function of dystrophin in nerve cells, it is believed that protein is important for the structure and normal function of synapses.
They have identified more than 1,000 mutations in the DMD gene in affected individuals Duchenne muscular dystrophy and Becker. Most mutations eliminate part of the DMD gene (65% of DMD and BMD 55%) with extensive deletions of one (18%), or more (78%), gene exons. Most deletions occur between exons 8 and 13 and between exons 45 and 52. Other mutations abnormally duplicated part of the gene or cause specific changes in some nucleotide sequence (30% of cases). Mutations that cause Becker muscular dystrophy, usually result in an abnormal version of dystrophin that maintains some function, while mutations responsible for Duchenne muscular dystrophy generally inhibit any functional protein encoding. Therefore, cells of skeletal and cardiac muscle without sufficient functional dystrophin damaged when the muscles contract and relax repeatedly. Damaged cells weaken and eventually die, resulting in the characteristics of muscle weakness and heart problems seen in muscular dystrophy Duchenne and Becker.
This disease is inherited X - linked recessive In males, who have only one X chromosome, the alteration in this chromosome is sufficient to express the disease. In women with two X chromosomes, the mutation must be present on both chromosomes to express the disease. Because it is unlikely that women have two altered copies of this gene, males are affected by recessive X - linked disorders much more frequently than women. A feature of the X - linked inheritance is that fathers can not pass X - linked traits to their sons chromosome. In many cases, an affected male inherits the mutation from his mother, who carries an altered copy of the DMD gene. In all other cases the disease is probably due to new mutations in the gene in affected males and not inherited. In X - linked recessive inheritance, a woman with a mutated copy of the gene in each cell is called a carrier. She can pass the altered gene, but usually has no signs and symptoms of the disease. However, sometimes women who carry a mutation in the DMD gene may have muscle weakness and cramps. These symptoms are usually milder than muscle weakness and atrophy in affected males. Women who carry a mutation DMD gene also have an increased risk of developing cardiac abnormalities including cardiomyopathy.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Duchenne muscular dystrophy and Becker, by complete PCR amplification of the exons of the DMD gene, and subsequent sequencing. Being a large gene, they may follow several strategies for study. To detect deletions test conducted quantitative real - time PCR (qPCR Real Time). To detect point mutations, and with the aim of reducing the cost of testing, we propose a strategy based on the frequency of mutations found in genetic studies of these patients. The first stage is the study recommended exons 8-13 (exon 6), and 45 to 52 (8 exons). If not found alteration in these exons, we propose perform sequencing at different stages, for groups of 10 exons, in order to stop the study when mutations are found.
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) if postnatal diagnosis. Prenatal diagnosis amniotic liquid.