DGH - Dissertações de mestrado
Permanent URI for this collection
Browse
Browsing DGH - Dissertações de mestrado by advisor "Almeida, Adelaide"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- Nova abordagem no estudo da Distrofia Muscular das Cinturas tipo 2APublication . Maia, Nuno; Oliveira, Márcia E.; Almeida, AdelaideMuscular dystrophies comprise a group of heterogeneous genetic diseases characterized by progressive muscle weakness. Until now, eighteen genes have been associated to a specific subgroup of muscular dystrophies called limb-girdle muscular dystrophies (LGMD). Mutations in the CAPN3 gene are responsible for calpainopathy or limb-girdle muscular dystrophy type 2A (LGMD2A), one of the most frequent form of LGMD. The gene CAPN3 codes for calpain 3 (or CAPN3), a muscle-specific calcium-dependent cysteine protease functionally regulated via its autolytic activity. The pathogenesis mechanism of LGMD2A still continues to be unresolved, however functional defects of CAPN3 seem to be the major cause of the pathology. With the present work, it is proposed a new approach for the LGMD2A diagnostic analysis, combining molecular genetics and protein analysis methodologies in order to contribute to a differential diagnostic essential for global characterization of patients, specifically among patients with non-specific muscular dystrophy symptoms. Muscle biopsy samples of 9 LGMD2A patients, already studied at the molecular genetics level, were subjected to protein analysis and functional tests by western blotting and densitometry analyses. Additionally, gene expression studies were performed using real-time quantitative PCR. A global analysis of the data obtained allowed us: (a) to complement the previous molecular genetics study in patients 2-7, including the identification of a CAPN3 functional defect in patient 3; (b) to confirm the clinical diagnostic in patient 8 (with only one mutation in heterozygous state) also caused by a protein functional defect; and (c) to exclude the CAPN3 implication in the other two patients which presented one mutated allele in heterozygous state, because of the detection of an overexpression of the CAPN3 gene in comparison to control samples.