Identificación de genes de susceptibilidad en esclerosis múltiple. Descripción clínica y análisis genético de una extensa familia de etnia gitana (Estudio EMGypsy)

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Multiple sclerosis is a chronic disease of the central nervous system which has an unknown aetiology and an autoimmune mechanism. Two pathogenic processes, inflammation and neurodegeneration, converge causing a progressive disorder with a high degree of both physical and cognitive disability. The disease is the most frequent cause of non-traumatic neurological disability in the young adult population in the Western world. Epidemiological and natural history studies show that there is a genetic susceptibility to the disease upon which a number of environmental factors act, generating an imbalance in the immune system that eventually produces a central nervous system attack with the consequent manifestation of the characteristic signs and symptoms of the disease. However, the inherited aspect of the disease has yet to be completely elucidated, suggesting that the genetic burden is probably hidden in the form of a rare variant inside a family cluster or as an epigenetic factor that is responsible for regulating the expression of genes at the disease onset. In this doctoral thesis a large Romani family with an inherited form of multiple sclerosis has been studied clinically and genetically. The high number of affected members, the presence of several clinical forms and the ethnic characteristics of the family (with considerable inbreeding and a consequently high level of homozygosity) make it an exceptional, isolated population for the study of new genetic substrates associated with the disease. The results of this doctoral thesis reveal certain genetic variants, some of which have not been previously described, are significantly more frequent in the family members with MS than in unaffected subjects, suggesting that there are several candidate genes involved in the development of the disease in this particular family ​
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