Duchenne Muscular Dystrophy at the Cellular Level

Causes 

People did not know much about the cause of this disorder until the year 1980s. However, individuals were not aware of muscular dystrophy forms. Yiu & Kornberg (2015) discuss that after that in 1986, researchers, supported by MDA, discovered the X-chromosome gene, which when muted, leads to two muscular dystrophies (Duchenne and Becker). An essential biological component, gene, encompasses codes/recipes for proteins. After one year, researchers discovered the protein connected to this gene, which is dystrophin. The disorder occurs because of failure of gene mutation to generate functional dystrophin. On the contrary, people with Becker Muscular Dystrophy genetic mutations produce dystrophin, which is functional. The lack of dystrophin makes people weak because of muscles damage during the early stage of childhood. 

Protein dystrophin conveys the power of muscle contraction from the interior of the cell’s muscle outside the cell membrane. Since it links the middle of the muscle cell to the periphery, it is long ( Falzarano et al., 2015) . The first end of dystrophin is specialized for connecting the muscle interior side while the other end connects several proteins at the cell membrane. A couple of repeating units known as spectrin repeats carries rod domain, which is the long middle section, away. The repeating units play an essential role in joining the two ends of dystrophin. Besides, research has shown that the same number of the units is not crucial to the role of the protein. However, several studies state that the cause of DMD is by variation in the gene section that encodes the middle part. Protein production stops while encountering the process of mutation, Lack of dystrophin causes the motion deleterious effects formation of fibrous tissue occurs in the muscle, and the immune system rises inflammation. 

Duchenne Muscular Dystrophy Inheritance

X-linked pattern inherits Duchenne Muscular Dystrophy since the gene carrying a Duchenne Muscular Dystrophy- causing mutation is on X chromosome. Mothers transfer X chromosome to each boy and fathers Y chromosome, which determines males. For girls, both X chromosomes are from both parents ( Bladen, 2008) . Boys with this kind of dystrophin protein have a 50% chance of receiving the muted gene thus suffer DMD. Girls can only be carriers of the disorder, with 50% of inheriting the flawed gene. Children born by carriers inherit the flawed gene and can be at risk of suffering cardiomyopathy. A family without any account of the disorder can bear sons with the disease. There are two possible reasons. Bladen (2008) discusses that the first reason is that gene mutation can occur from one generation to another for an extended time in families where there are no girls. Secondly, new genetic mutation can happen from egg cells of a mother. Therefore, the mutation is not in the blood of the mother and deleting using standard carrier testing is impossible.

Chances of a mother having several of her egg cells with dystrophin are high if she gives birth to a child with the condition ( Sussman, 2002) . However, passing the mutation to another child is very high. The new mutation is hereditary because it passes through one generation to another. Since a man passes Y chromosomes to his sons, it is impossible to transfer DMD to his sons. To the girls, it is possible to transfer the disorder because they inherit the X chromosomes from their father with DMD. 

Females and DMD

Girls who inherit the mutation from one parent normally get dystrophin protein, which is healthy from the other parent thus supplying enough protein to prevent her from the disorder ( Bladen, 2008) . On the contrary, males do not have second dystrophin gene to replace the faulty one. During the early stages of embryonic growth of a female, inactivation of either paternal X or maternal X occurs. Inactivation choice, in this case, is random thus; chances of inactivation of X chromosome is 50%. X chromosome gene mutation is crucial unlike X chromosome from paternal or maternal. Symptoms of DMD or BMD can develop if a girl or a woman relies much on several X chromosomes with the dystrophin gene mutation. Yiu & Kornberg (2015) note that in this way, girls do not suffer full influence of DMD as compared to boys. However, they might all have muscle weakness symptoms. Females with manifesting carriers mutation show signs and symptoms to this disorder, and they are scarce.

Females with manifesting carriers suffer dystrophin deficiency in weaker muscles in the back, arms, and legs that get tired easily ( Robinson-Hamm, & Gersbach, 2016) . Carriers with this mutation can have issues of the heart that can erupt as breathing difficulties or inability to do limited exercises. Failure of treating the heart problem can cause death, thus, taken seriously. Girls who do not have the second X chromosomes or damaged X chromosomes are few. In this way, the victim produces little or no dystrophin and can get DMD or BMD same as a boy. Such a girl/female should receive the same diagnostic tests to find out the carrier status. 

Statistics

Based on Duchenne Muscular Dystrophy statistics, prevalence differs regarding ethnicity or race. It shows that socioeconomic and cultural effects the impacts on the treatment of the disorder ( Yiu & Kornberg, 2015) . Age ranges, racial variations, and diagnostic methods differ in a given population. The rate of infection to boys is high since they only have one X chromosome, while girls are not highly affected for they have two X chromosomes. The disorder occurs in 1:35000 ratio simplifying one female in every thirty-five hundred males in the world. For example, in the United States, the estimated rate is 0.02% for infected people. Yiu & Kornberg (2008) assert that this disorder majorly affects boys with six years. Also, people can see the symptoms in kids at the stage of infancy.

Transmission pattern

The transmission pattern of DMD is gene mutation from parents to offsprings. X-linked pattern inherits Duchenne Muscular Dystrophy since the gene carrying a Duchenne Muscular Dystrophy- causing mutation is on X chromosome. Aartsma‐Rus et al. (2009) show that mothers transfer X chromosome to each boy and fathers Y chromosome, which determines males. For girls, both X chromosomes are from both parents. Boys with this kind of dystrophin protein have a 50% chance of receiving the muted gene thus suffer DMD. Girls can only be carriers of the disorder, with 50% of inheriting the flawed gene. Children born by carriers inherit the flawed gene and can be at risk of suffering cardiomyopathy

Symptoms

One can only recognize this disorder, when a child has challenges when either running, standing or climbing. The disorder begins in childhood as parents genetically transfer the condition to children ( Matthews et al., 2016) . Majorly, the condition affects boys only. However, girls can carry the disorder gene but not affected. Before turning six years old, one can recognize the first signs. The affected child usually has difficulties in climbing stairs, falling often, and walking on toes.

Treatments

DMD has no cure. One can apply therapy to reduce the symptoms of the affected child as well as medicine use ( Bladen et al., 2010) . Besides, the approved Eteplirsen can assist in treating individuals with DMD gene mutations. The injection has side effects like vomiting and problems in balancing. Lastly, oral corticosteroid treats this disorder by increasing strengths of muscles and maintaining stability to the affected ( Bladen, 2008) .

Important historical note

First known people with this disorder were the boys who grew weak and later on died at an early stage. According to Yiu & Kornberg (2015), they were the first to have this disorder thus common in medical journals. Guillaume Duchenne provided a history of different forms of the disorder thus the disease named after him. The disease had an impact on the society thus people some scientists and associations provided guidance and awareness to DMD. Several associations promote awareness of this disorder. For instance, Muscular Dystrophy Association, National Institute of Neurological Disorders, National Institute of Child Health and Human Development, and others

Discussion

Duchenne muscular dystrophy at the cellular level is important to me for the following reasons; the topic facilitates learning as well as building knowledge, the topic helps in understanding various issues and increasing public awareness, doing research is a means to discover and seize opportunities thus nurturing potential and achievable goals. However, DMD is an essential disorder, which is genetically transferred from parents to children thus helps in understanding through knowledge of research and information like its influence in each 3500 male born worldwide. In this way, people worldwide in finding treatment, causes, history, and detailed information concerning the disorder can use the results.

References

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Biggar, W. D. (2006). Duchenne muscular dystrophy.  Pediatrics in Review ,  27 (3), 83.

Bladen, C. L., Salgado, D., Monges, S., Foncuberta, M. E., Kekou, K., Kosma, K., ... & Guergueltcheva, Manzur, A. Y., Kuntzer, T., Pike, M., & Swan, A. V. (2008). Glucocorticoid corticosteroids for Duchenne muscular dystrophy.  Cochrane database of systematic reviews , (1).

Bushby, K., Finkel, R., Birnkrant, D. J., Case, L. E., Clemens, P. R., Cripe, L., ... & Poysky, J. (2010). Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management.  The Lancet Neurology ,  9 (1), 77-93.

Emery, A. E., Muntoni, F., & Quinlivan, R. C. (2015).  Duchenne muscular dystrophy . OUP Oxford.

Falzarano, M., Scotton, C., Passarelli, C., & Ferlini, A. (2015). Duchenne muscular dystrophy: from diagnosis to therapy.  Molecules ,  20 (10), 18168-18184.

Matthews, E., Brassington, R., Kuntzer, T., Jichi, F., & Manzur, A. Y. (2016). Corticosteroids for the treatment of Duchenne muscular dystrophy.  The Cochrane Library .

Robinson-Hamm, J. N., & Gersbach, C. A. (2016). Gene therapies that restore dystrophin expression for the treatment of Duchenne muscular dystrophy.  Human Genetics ,  135 (9), 1029-1040.

Sussman, M. (2002). Duchenne muscular dystrophy.  JAAOS-Journal of the American Academy of Orthopaedic Surgeons ,  10 (2), 138-151.

Yiu, E. M., & Kornberg, A. J. (2015). Duchenne muscular dystrophy.  Journal of paediatrics and child health ,  51 (8), 759-764.