Duchenne muscular dystrophy (DMD) is an X-linked recessive disease, affecting 1 in 3500 males (Roland, 2000). DMD was first described by the French neurologist Duchenne de Boulogne, and thus named after him (Sex-Linked Diseases: The Case of Duchenne Muscular Dystrophy (DMD) ½ Learn Science at Scitable, undated). This neuromuscular disease is characterized by progressive deterioration and weakness of skeletal and cardiac muscles, which affects patients' movements. Although DMD typically affects males, there are 20-30 females worldwide who are affected by this disease due to translocations in the X chromosome (Strachan and Read, 2010, p. 520). Symptoms of DMD will first be seen around 3-5 years of age. An observable symptom of DMD is increased size of the calf muscles. Many other common symptoms include weakening of the pelvic muscles, lack of balance, and difficulty climbing stairs (Roland, 2000). By age 12, most patients would be confined to a wheelchair. People with Duchenne muscle disease typically die before reaching reproductive age, around age 20, due to heart or breathing difficulties (Fairclough, Bareja, & Davies, 2011). This disease is caused by the absence of the dystrophin protein. Say no to plagiarism. Get a tailor-made essay on "Why Violent Video Games Shouldn't Be Banned"? Get an original essay The dystrophin gene is the largest human gene located on chromosome Xp21, which is 2.4 kb, containing 79 small exons. The gene encodes the 427 kDa cytoskeletal dystrophin protein (Michalak and Opas, 2001). The dystrophin gene has at least 7 different promoters, where different cells use different promoters for transcription to occur. Along with alternative splicing of introns, gene transcription is highly complex and varies from tissue to tissue (Sudbery and Sudbery, 2009, pp. 166). Consequently, the dystrophin gene is capable of encoding different isoforms of the dystrophin protein. The predominant isoform of dystrophin is expressed primarily in skeletal muscle cells, with traces present in brain cells (Michalak and Opas, 2001). Dystrophin has a long, slender, rod-like shape (Thakur, 2015). The protein has four domains, namely the NH2 domain, the central rod domain, the cysteine-rich domain, and the COOH-terminal domain, as shown in Figure 1 (Blake et al., undated). Figure 1. Structure of the dystrophin glycoprotein complex present in the sarcolemma of skeletal muscle cells. Dystrophin binds to the actin cytoskeleton at the NH2 terminus while the COOH terminus interacts with other membrane proteins. The dystrophin protein plays a crucial role in the mechanical and structural function of the muscle membrane, also known as the sarcolemma (Thakur, 2015). Dystrophin does this by stabilizing the muscle membrane and maintaining the shape of muscle cells. Dystrophin also binds to the cytoplasmic region of the sarcolemma, as part of a glycoprotein complex. This transmembrane complex is known as the dystrophin-glycoprotein complex (DGC). DGC is a multimeric protein that connects the actin components of the cytoskeleton, basal lamina, and plasma membrane. As a result, force can be transmitted through the cell providing mechanical stability during muscle contraction, producing movement. Membrane stability is ensured by increasing membrane rigidity and preventing rupture of the sarcolemma (Thakur, 2015). The DGC plays a role in the organization of the cytoskeleton and also provides a signaling pathway between the connective tissue andthe cytoskeleton of muscle cells (Michalak and Opas, 2001, Sudbery and Sudbery, 2009, pp. 165-167). Dystrophin also maintains a regular supply of calcium ion concentration and is used for cell signaling (Thakur, 2015). A regular concentration of calcium ions is essential for the contraction cycle to occur in the muscles. Upon arrival of the action potential at the sarcolemma, the release of calcium ions is triggered. This creates tension in the muscle tendons (Martini, Nath, & Bartholomew, 2014, pp. 329). Calcium ions act as a second messenger for the G protein and receptor tyrosine kinase pathways during cell signaling. The cellular response of these pathways would result in the contraction of muscle cells (Urry, Cain, & Reece, 2011, pp. 263). Deletions in the dystrophin gene cause 60-70% of cases of Duchenne muscular dystrophy. As a result of the deletion, one or more of the 79 exons would be lost. Other causes of mutations that result in the absence of dystrophin are duplications and small point mutations. These represent 10% and 15-30% of cases, respectively (Characterizing mutations of the dystrophin gene, no date). Duplications in the dystrophin gene cause one or more of the 79 exons to be repeated. Exon deletions and duplications in sequences coding for the –NH2 domain or the –COOH domain would result in a frameshift mutation, producing truncated proteins (Michalak and Opas, 2001, Sudbery and Sudbery, 2009, pp. 165–167). The resulting protein is truncated and unstable. Therefore, the protein would not perform its normal function, resulting in the DMD phenotype. However, large deletions occurring in the rod domain of the protein do not produce any serious effects that could lead to DMD (Blake et al., 2002). In the absence of dystrophin, the dystrophin-glycoprotein complex would not form as a result, affecting muscle cell integrity and therefore muscle function (Michalak and Opas, 2001, Sudbery and Sudbery, 2009, pp. 165-167). To produce locomotion, muscles repeatedly contract and relax. Damaged muscle fibers weaken, causing the muscle fibers to gradually die. Over time, weakening of the muscles makes the patient more susceptible to injury (Duchenne and Becker muscular dystrophy – Genetics Home Reference, 2015). Muscle deterioration then leads to membrane loss, causing an influx of calcium ions and creatine kinase into the blood (Blake et al., 2002, Michalak and Opas, 2001). Due to the influx of calcium ions, the contraction cycle could not occur. Creatine kinase is an enzyme that catalyzes the transfer of energy from ATP to creatine in skeletal muscle cells. High concentration of creatine kinase indicates muscle damage. (Martini, Nath and Bartholomew, 2014, pp. 329). Prospective parents can use genetic testing to understand their Duchenne muscular dystrophy carrier status, if there is a high probability of having an affected child, before making any decisions about reproduction (Sudbery and Sudbery, 2009, pp. 297) . Genetic testing for DMD can be performed through multiplex polymerase chain reaction (PCR) testing of the dystrophin gene. Deletions in the dystrophin gene primarily affect exons 3-8 or exons 44-60. A mixture of different DMD gene primer pairs is used for this reaction. Each primer pair was designed to amplify a specific exon. Once the reaction is complete, you would see one band for each exon present. A missing band indicates that the exon has been deleted (Sudbery and Sudbery, 2009, pp. 307). Other ways to check if a patient has Duchenne muscular dystrophy include the. 166).