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Departamento de Genética Humana

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Browsing Departamento de Genética Humana by advisor "Amaral, Olga"

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  • Estudo molecular de Epilepsia Mioclónica Progressiva de Unverritch -Lundborg
    Publication . Pinto, Eugénia; Amaral, Olga; Santos, Manuel
    The Progressive Myoclonus Epilepsies (PME) are associated to an heterogeneous group of rare metabolic diseases. They are clinically marked by myoclonic, tonic-clonic episodes and progressive neurological decline, with ataxia and dementia. One of the major causes of PME is the Unverricht- Lundborg disease (EPM1, MIM 254800), an autosomal recessive disorder, caused by loss of function mutations in the cystatin B gene (CSTB). The onset of the symptoms is around the age of 10 yr. and is marked by convulsions. The EPM1 diagnostic is done through a differential diagnostic, first at a clinical level, and being confirmed at a genetic level. The main objective of this work is the implementation of the genetic study and applied research in EPM1. Since EPM1 is a rare disease without laboratory diagnostic in Portugal its real impact at the level of public health is unknown, the methods developed in this thesis will give the possibility of confirming/excluding clinical suspicion of EPM1, and allow the characterization of the patients. The results obtained have permitted the initiation of the study of CSTB, in instances where there was a suspicion of EPM1. It became possible to confirm a case of a patient suspect of having the EPM1, as well as making the evaluation of some polymorphisms present in our population. The new mutation, found and characterized in this work, is a point mutation, apparently silent (p.Q22Q), which alters the normal splicing pattern resulting in partial retention of the intronic sequence and subsequently leading to loss of function. These results show the need for making a non directional approach, doing a comprehensive study of the CSTB gene and complementing the gDNA study with the cDNA one. The study of this disease at the molecular biology level, may contribute to the evaluation and characterization of this pathology as far as its mutations and, at same time, it may contribute for a better understanding of its pathophysiology.
    2010-12Master thesis Restricted access Show more