Test Design for Oculopharyngeal Muscular Dystrophy INTRODUCTION: Oculopharyngeal muscular dystrophy (OPMD) is an inherited neuromuscular genetic disorder. It has an autosomal dominant pattern of inheritance (Fried et al. 1975) in that the abnormal gene can be transmitted from only one parent. A child of an affected parent has a 50% chance of being affected. The disorder is found to be more prevalent among French-Canadians and is characterized by its late onset (approximately 50). Affected persons experience dropping eyelids (optosis), difficulty with swallowing (dysphagia), and some develop shoulder, hip or leg weaknesses (MDA publications 1998). Genetically, its mutation is quite unique. OPMD is caused by the expansion of a GCG (which codes for the amino acid alanine) 6 repeat (Brais et al. 1998), whereas most triplet repeat disorders are expansions of CAG (glutamine) repeats. Rare polymorphisms would be to have 7 consecutive GCG's, but the disease is mostly characterized by the mutation of having 8-15 consecutive GCG's. Other findings have shown that even the expansion of a 6 GCG repeat to 7 can also lead to OPMD (LaFontaine 1996). The severity of the disease depends on the number of extra alanines. Quite recently, scientists have found that the mutation occurs on chromosome 14 and is in the gene coding for a poly(A)-binding protein 2 gene (PABP2) (Brais et al. 1998). PABP2 was considered a good candidate for OPMD because it maps to the same location as the diseased gene, its mRNA is highly expressed in skeletal muscle, and the PAB2 protein is exclusively localized in the nucleus, where it acts as a factor in mRNA polyadenylation. The site of the additional GCG expansions in the PABP2 gene is at the polyala... ... middle of paper ... ... F.; Lafreniere, R.; Rommens, J; Uyama, E.; Nohira, O.; Blumen, S.; Korcyn, A.D.; Heutink, P; Mathieu, J; Duranceau, A.; Codere, F.; Fardeau, M.; Rouleau, G.A. (1998) Short GCG expansions in the PABP2 gene cause oculopharyngeal muscular dystrophy. Nature Genet, 18: pp164-167. Fried, K.; Arlozorov, A.; Spria, R. (1975) Autosomal recessive oculopharyngeal muscular dystrophy. J. Med. Genet. 12: pp416-418. LaFontaine, G. (Feb 24, 1996) Quebec's common muscular dystrophy gene mutation found. Medical Post: pp20. MDA Publications (http://www.mdausa.org/publications/Quest/q5resup.html) (Feb. 1998) Research Updates. Quest vol.5, number 1. Rifugo, G. et al. (1997) Survey of maximum CTG/CAG repeat lengths in human and non-human primates: Total genome scan in population using the Repeat Extension Detection method. Human Molecular Genetics 6:3 pp403-408.
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1. James suffers from a condition called Duchenne muscular dystrophy. Explain the full meaning of this name.
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The first historical account of muscular dystrophy was identified by Sir Charles Bell in 1830. He wrote about a disease that caused weakness in boys that progressively got worse. In 1836 another scientist whose name is unknown reported about two brothers who developed muscle damage, generalized weakness. Also damaged muscle was replaced with fat and connective tissue. At the time the symptoms were thought to point to tuberculosis. During the 1850s reports of boys with progressive muscle weakness became more and more common. There were also reports of these boys losing the ability to walk and dying at an early age. In the next decade French neurologist Guillaume Duchenne gave and in depth account of 13 boys who had the most common ...
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