Information de reference pour ce titreAccession Number: | 00006114-201103010-00007.
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Author: | Disanto, G. MD *; Magalhaes, S. MSc *; Handel, A.E. MD; Morrison, K.M. MSc; Sadovnick, A.D. PhD; Ebers, G.C. MD; Banwell, B. MD; Bar-Or, A. MD; On behalf of the Canadian Pediatric Demyelinating Disease Network
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Institution: | From the Wellcome Trust Centre for Human Genetics (G.D., A.E.H., K.M.M., G.C.E.) and Department of Clinical Neurology (G.D., A.E.H., K.M.M., G.C.E.), University of Oxford, Oxford, UK; Neuroimmunology Unit (S.M., A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec; Department of Medical Genetics and Faculty of Medicine (A.D.S.), Division of Neurology, University of British Columbia, Vancouver; Department of Paediatrics (B.B.), Division of Neurology, The Hospital for Sick Children, University of Toronto, Toronto; and Experimental Therapeutics Program (A.B.-O.), Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
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Title: | |
Source: | Neurology. 76(9):781-786, March 1, 2011.
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Abstract: | Background: Multiple sclerosis (MS) in the pediatric age group is being increasingly recognized. In adults, complex interactions between genetic and environmental factors contribute to risk and the major genetic component of MS susceptibility localizes to the major histocompatibility complex (human leukocyte antigen [HLA]). Whether HLA alleles predict MS in at-risk children presenting with acquired demyelinating syndromes (ADS) of the CNS is unknown.
Methods: HLA-DRB1 alleles were typed using an allele-specific PCR amplification method on samples from 266 children presenting with ADS enrolled in the prospective Canadian Pediatric Demyelinating Disease Study and from 196 healthy controls.
Results: Sixty-four of 266 children with ADS met established criteria for a diagnosis of MS during a mean follow-up of 3.2 +/- 1.5 years. Children harboring DRB1*15 alleles were more likely to be diagnosed with MS ([chi]2 = 12.2, p < 0.001; OR = 2.7), an observation strengthened by children of European ancestry ([chi]2 = 10.5, p = 0.001; OR = 3.3). DRB1*15 allele frequencies in children with ADS of European ancestry subsequently diagnosed with MS were greater than in children with monophasic ADS ([chi]2 = 10.7, p = 0.001) or healthy controls ([chi]2 = 12.5, p < 0.001). The proportion of children with non-European ancestry diagnosed with MS was not influenced by DRB1*15 status.
Conclusion: DRB1*15 alleles confer increased susceptibility to pediatric-onset MS, supporting a fundamental similarity in genetic contribution to MS risk in both pediatric- and adult-onset disease. The specificity of the DRB1*15 risk allele for children with subsequent MS diagnosis, but not for all children with ADS, indicates that the risk conveyed by DRB1*15 relates to chronic CNS disease (MS), rather than acquired demyelination in general.
(C)2011 American Academy of Neurology
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Language: | English.
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Document Type: | Articles.
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Journal Subset: | Clinical Medicine. Life & Biomedical Sciences.
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ISSN: | 0028-3878
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NLM Journal Code: | 0401060, nz0
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DOI Number: | https://dx.doi.org/10.1212/WNL.0...- ouverture dans une nouvelle fenêtre
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