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| Author(s): |
Natale Cavaçana
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB) |
| Defense date: | 2014-11-07 |
| Examining board members: |
Mayana Zatz;
Débora Romeo Bertola;
Luciane Portas Capelo;
Fernando Kok;
Mariz Vainzof
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| Advisor: | Mayana Zatz |
| Abstract | |
The hereditary spastic paraplegia (HSP) is characterized by muscle weakness and lower limb spasticity. They are very heterogeneous both clinically and genetically. Several forms have been described and the most common one, affecting around 40% of autosomal dominant cases, is caused by mutations in the SPAST gene (HSP type 4 or SPG4). Genotype: phenotype correlation studies have shown that affected individuals from the same family, who carry the same pathogenic mutation, can have very distinct phenotypes. The underlying explanation behind this clinical heterogeneity may be found in the search for modifier genes, in expression patterns observed proteomic analyses (either by protein binding or folding), or epigenetic mechanisms. As is observed in other motor neurodisease, there is a disproportion between the number of affected males and females, with males being the predominantly affected. The objective of this study was to analyze discordant patients, i.e., those that possess the same mutation, but show discordant phenotypes, from a large Brazilian family with SGP4. For this study, the abundance of transcripts (mRNA) and genotype (single nucleotide polymorphisms) relative to a phenotype (symptomatic or asymptomatic) were analyzed. The results suggest that the main system involved, which could explain the differences between discordant patients, is the immune system, with the main activity of C2, LY6G6C and HLA-DRB1 genes. These genes may have a protective or toxic role in the development of the analyzed patients\' clinical features (AU) | |