Congenital Muscular Dystrophies (CMDs) are a heterogeneous group of conditions that usually present in the first months of life with weakness and hypotonia. Extramuscular manifestations are common and may include brain, skin and eye abnormalities. CMDs are relatively rare disorders and despite the major progress made over the last 2 decades in identifying, mapping and investigating these conditions, there remains a lot to be learned. Little is known about the relative frequency of the various forms of CMD in the UK population. Experience had shown that founder mutations are common in different ethnic populations and epidemiological studies performed in other countries are of limited value in this regard. Since 2001, the Dubowitz Neuromuscular Centre (DNC) has been the National Commissioning Group UK Centre for CMD. As such we are in the privileged position to have access to a large number of UK patients with CMD. I analysed a cohort of 214 CMD referrals to the DNC between 2001 and 2008 with a view to reporting the diagnostic outcome and the frequency of the various forms of CMD encountered in our patient population. The second part of the thesis is concerned with the dystroglycanopathies, a recently described group of CMDs associated with aberrant glycosylation of alpha dystroglycan. To date, 7 genes have been identified, some of which give rise to multiple dystroglycanopathy phenotypes. I studied the genotype-phenotype relationship in a large group of dystroglycanopathy patients, reporting new clinical phenotypes and establishing the mutation frequency in this group. I also report in detail the spectrum of MRI brain changes seen in 27 dystroglycanopathy patients. In summary, this work reports the diagnostic outcome in the largest cohort of UK CMD cases studied and refines the genotype-phenotype correlation in patients with dystroglycanopathies.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:565347 |
| Date | January 2011 |
| Creators | Clement, E. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1318071/ |
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