Mémoire (M.Méd.Exp.)--Université du Québec à Chicoutimi, 2001. / Document électronique également accessible en format PDF. CaQCU

Thèse (M.Med.Exp.) -- Université Laval, extensionné à l'Université du Québec à Chicoutimi, 1999. / Bibliogr.: f. 68-73. Document électronique également accessible en format PDF. CaQCU

Thesis (MAppSc)--University of South Australia, 1996

Thesis (MAppSc)--University of South Australia, 1996

Thesis (Ph.D.) - University of Glasgow, 2008. / Ph.D. thesis submitted to the Division of Molecular Genetics, Institute of Biomedical and Life Sciences, University of Glasgow, 2008. Includes bibliographical references. Print version also available.

Thesis (Ph. D.)--University of Oregon, 2008. / Typescript. Includes vita and abstract. Includes bibliographical references (leaves 93-106). Also available online in Scholars' Bank; and in ProQuest, free to University of Oregon users.

Myotonic dystrophy is the commonest form of adult muscular dystrophy. Myotonic dystrophy 1 and 2 (DM 1 and DM 2) are autosomal dominant inherited disorders with unusual multisystem clinical features characterized by myotonia, progressive muscle weakness and wasting, cataracts, hypogonadism, frontal balding, cardiac conduction defects and diabetes. Severity varies from asymptomatic to severely affected phenotypes. DM1 presents with predominantly distal weakness whereas DM2 have predominantly proximal weakness.98% of patients identified worldwide present with DM1. DM 1 is caused by the expansion of an unstable CTG trinucleotide repeat in the 3' untranslated region of the myotonic dystrophy protein kinase gene on chromosome 19ql3.3. DM 2 is linked to the long arm of chromosome 3q21. It is caused by a tranucleotide, CCTG expansion in intron 1 of the zinc finger protein 9(ZNF9) gene that interferes with processing of a variety of RNAs. All DM mutations can be detected using a combination of the Southern Blot and Polymerase Chain reaction (PCR) techniques. Aim: This study aims to characterize the clinical spectrum and molecular features of myotonic dystrophy patients in KwaZulu - Natal between 1989 and 2005. Methodology: Patients included in this study were obtained from the database of patients diagnosed with Myotonic Dystrophy at the Department of Neurology in KwaZulu-Natal from 1989 to 2005. Patients were subjected to clinical, radiological and neurophysiological assessment. Molecular testing was performed using PCR and Southern blot. Results: Thirty-seven patients with Myotonic Dystrophy were identified. Twenty patients consented and were included into the study. Eighty-five percent of patients were of Indian descent and the remaining fifteen percent were White. No African patients were identified. Sixty-five percent were male and thirty-five percent female. Myotonia was clinically present in all patients. Ninety-five percent of patients presented with predominantly distal weakness of which 40% demonstrated mild weakness, 35% moderate weakness and 25 % severe weakness. No patients were identified with predominantly proximal wasting or weakness. Southern blotting demonstrated expanded CTG repeats (DM1) in all 20 samples analysed. The PCR analysis was unable to demonstrate expanded alleles. Conclusion: This study identified patients presenting with Myotonic dystrophy to the Department of Neurology in KwaZulu-Natal and demonstrated that Myotonic Dystrophy Type 1 remains the commonest clinical and molecular presentation. In addition it substantiated previous research findings wherein no South African of African descent was found to be affected by the disease. There have been no reported cases of Myotonic Dystrophy in African Black patients presenting to the Department of Neurology in Durban, no African Black patients have been diagnosed with Myotonic Dystrophy over the past 20 years. However ,the predominance of Indians in this study is more likely a reflection of referral bias than differing incidence amongst sections of the population. PCR analysis cannot detect trinucleotide repeat expansions beyond 200 repeats and as a result Southern Blotting remains the gold standard in obtaining a molecular diagnosis. A clinical diagnosis is sufficient and molecular confirmation is not an absolute requirement. / Thesis (M.Med)-University of KwaZulu-Natal, Durban, 2006.