Dystrophin Analysis

Duchenne Muscular Dystrophy is a disease which causes skeletal muscle to waste away, this wasting of muscle is caused by a mutation of the dystrophin gene (Meregalli et al., 2013, p. 4251).

Occurrence of muscle dystrophy is estimated to be one in 3-4,000 male births. There are also about 15,000 muscular dystrophy patients in the United States today with this disease. Those who have muscular dystrophy are missing the protein called dystrophin. Before scientists ever discovered the missing protein, the tested carriers for the disease had a high presence of elevated serum levels of creatine and phosphokinase. The disease can now be found for a prenatal diagnosis.

Duchenne muscular Dystrophy (DMD) is the most common out of nine types of muscular dystrophy. This genetic disorder causes progressive muscular weakness, and deterioration due to the lack of a protein called Dystrophin. This protein keeps the muscles in tack, so when it's missing, the muscles slowly break down. (MDA, 2015)

Duchenne Muscular Dystrophy is a sex-linked disease, which is inherited in a recessive fashion (National Human Genome Research Institute, 2013). Over thirty similar genetic disorders exist (Duchenne Foundation Australia, 2015). All types of muscular dystrophy are considered to be a rare disorder (Duchenne Foundation Australia, 2015). Duchenne Muscular Dystrophy is most common in children and causes muscle weakness and wasting, which commonly begins in the lower limbs (Duchenne Foundation Australia, 2015; National Human Genome Research Institute, 2013). The disease itself is caused by changes to the DMD gene, which is responsible for providing instructions regarding the creation of the dystrophin protein in one’s muscles (Duchenne Foundation Australia, 2015). This protein is responsible for protecting muscles from damage, and without it the cells of a person’s muscles deteriorate and symptoms of Duchenne Muscular Dystrophy are exhibited (Duchenne Foundation Australia, 2015). The disease results from changes in the DMD gene, or other genetic changes in a child (Duchenne Foundation Australia, 2015).

Duchenne Muscular Dystrophy is caused by a defect or a mutation in the DMD gene located in the X chromosome. This gene provides instruction for a protein that helps muscle tissue repair itself known as dystrophin. The absence of this protein is thought to be the cause of all types of muscular dystrophy. The genetic explanation of the defective gene is simple: males have one X and one Y chromosome and females have two X chromosomes, so when a female inherits the mutated gene she has another unchanged X chromosome make her asymptomatic or showing no symptoms or evidence of a disease or disorder. A female with one mutated and one normal gene is labeled a carrier and each child of hers born has a one in two chance of inheriting the gene. On the other hand, males have no extra X chromosome, so they have no protection against the symptoms. Because of these conditions, DMD is classified as an X-linked disorder and this is why DMD only affects boys.

The malfunction of the protein dystrophin is responsible for the symptoms of DMD. If the dystrophin gene functions correctly, the normal allele codes for the production of the protein dystrophin (“NCBI”). This is a high molecular weight protein, and it is in .002% of the total proteins. Normally, the dystrophin protein functions inside muscle cells, providing structural support. It anchors parts of the internal

Duchenne muscular dystrophy (DMD) is caused by a mutated gene in the X chromosome. This flawed genes is passed on by the mother. However, most carrier of the gene do not show signs or symptoms of the disease. The The flawed gene causes the improper production of the protein dystrophin which is accompanied by “defective dystrophin-glycoprotein complex (DGC) in the sarcolemma and leads to progressive muscle degeneration” (Nakamura & Takeda, 2011). The Dystrophin protein is vital in providing a muscle integrity. Therefore, the absence of dystrophin production can lead to muscled atrophy.

In Duchenne Muscular Dystrophy, the protein dystrophin has no function at all. Due to the fact that the protein has always been enabled, it causes the symptoms and diagnosis for Duchenne Muscular Dystrophy to be so severe and worsen quicker (Bushby pp.1). This is harmful because their muscles have no protection. The cells that make up the muscles require this protein to become strong and healthy. In comparison, Becker Muscular Dystrophy has the dystrophin protein who mildly functions. (B 2015 MDA). Since it makes a shortened form of the dystrophin they have much more protection of their muscles compared to a patient who has Duchenne Muscular Dystrophy. Resulting that Becker Muscular Dystrophy is not as severe as having Duchenne Muscular

This protein may play a role in the communication within cells, especially those of the heart, brain and skeletal muscles. It is believed that the protein is involved in the communication between cells and regulates the production and function of important structures inside muscles cells by interacting with other proteins. The DMPK gene is located on the long arm of chromosome 19 at position 13.3. It is between base pairs 45,769,708 and 45,782,556 making it 12848 base pairs long. It consists of a trinucleotide repeat of the nucleotide sequence CTG. Meaning that the nucleotides CTG are repeated multiple times. In a normal DMPK protein the number of CTG repeats ranges from 5-34. The mutation that causes myotonic dystrophy is known as trinucleotide repeat expansion, meaning it increases the number of times CTG is repeated in the gene. People with myotonic dystrophy can have 50 to 50,000 repeats, the more repeats an individual has the worse their symptoms are. The increased number of repeats produces an expanded version of mRNA, which then forms clumps inside the cell that interfere with the production of many other proteins. These clumps prevent muscle cells and cells in other tissues from functioning

Duchenne Muscular Dystrophy or DMD for short is a genetic disease that affects the skeletal muscles causing muscle degeneration and muscle wasting. Duchenne Muscular Dystrophy is an X-linked recessive chromosomal disease, which is caused by mutations in the DMD Gene (Regenerative Medicine). This Disease affects 1 in 3600 boys (Regenerative Medicine). A male born with this disease experiences respiratory dysfunction, trouble ambulation, cognitive impairment, some even experience premature death. Unfortunately, there is no cure for DMD, but there are research studies in the works for different therapies to help reverse this gene mutation and to elevate symptoms associate with this disease.

When looking at a potential therapy or cure, it is important to recognize exactly how the disease affects the body. Duchenne Muscular Dystrophy (DMD) is one of the most severe myopathies, or muscle diseases (Cacchiarelli et al). To be diagnosed with DMD, a patient must have a mutation in the dystrophin gene present (Muscular Dystrophy Association). Moreover, that mutation in the gene is what causes the lack of dystrophin synthesis. Dystrophin is protein in the body that keeps the muscles intact (Muscular Dystrophy Association). Therefore, a lack of dystrophin causes the muscles to deteriorate; which is identified as dystrophy. When the body lacks strong healthy muscle, it does not only become weak; the body itself begins to shut down. Our organs depend on the muscles that allow us to walk, eat, and breathe to provide energy, nutrients, and oxygen. For this reason, DMD eventually leads to a short life.

Dystrophin is a pole molded cytoplasmic protein and an indispensable part of a protein complex that associates the cytoskeleton of a muscle fiber to the encompassing extracellular grid through

Desmin is a type III intermediate filament protein that is muscle-specific and is found in all muscle types: smooth, cardiac, and skeletal. Autosomal dominant and autosomal recessive desmin gene mutations affect desmin (DES) and oftentimes αβ-crystallin (CRYAB), a chaperone for DES, which leads to a type myofibrillar myopathy, known as desminopathy (Goldfarb et al., 2010). Desmin is the most abundant IF protein in striated and smooth muscle cells and is one of the earliest markers of muscle development (Clemen et al., 2012). Desmin filaments are mainly located at the periphery of Z-disk of striated muscles and at the dense bodies of smooth muscle cells, and they have been thought to play a major role in the maintenance of structural and mechanical integrity of the contractile apparatus in muscle tissues (Paulin & Li, 2004). A dysfunctional desmin protein cannot properly interact with Z-discs, leading to abnormalities of sarcomere structure and problems with the formation of myofibrils (NIH, 2016). The resulting pathology, desminopathy, is one of the most common intermediate filament human disorders associated with mutations in closely interacting proteins (Goldfarb & Dalakas, 2009). This condition is defined as skeletal and cardiac myopathy characterized by the presence of chimeric aggregates in muscle fiber areas that consist of DES, CRYAB and other proteins (Goldfarb et al., 2010). While a few desmin-related

It is estimated that 1 in 8,000 people worldwide develop the disease known as DM-Myotonica (GHR). DM-Myotonica is an inherited disease that causes an abnormal DNA expansion, which in turn creates an over abundance of certain types of genes, and ultimately disrupts the integrity of normal muscle function within in several parts of the body (MDA). The meaning of the name of the disease bears roots in Greek medicine, specifically the abbreviation DM, standing for dystrophia myotonica; the term dystrophy means bad nutrition and myotonic refers to tonic muscle spasms, or the inability of the muscles to relax (MDA 2015). There are two types of DM-myotonica which are named MMD1 and MMD2. MMD1 is the more prominent of the two, but both result in abnormal

Dystrophin has no morphological characteristics. Dystrophin has no information on its metabolism. The environment does not matter for Muscular Dystrophy because it is a genetic