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Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/780

Título: Molecular characterization of Portuguese patients with pathologies related to the lysosomal multienzymatic complex: Sialidosis and Galactosialidosis
Autor: Coutinho, Maria Francisca
Lacerda, Lúcia
Prata, Maria João
Ribeiro, Helena
Alves, Sandra
Palavras-chave: Doenças Genéticas
Issue Date: Sep-2008
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: Backgroung/ Objectives: The functional activity of lysosomal enzymes sialidase, -galactosidase, and N-acetylaminogalacto-6-sulfate in the cell depends on their association in a multienzyme complex with lysosomal carboxipeptidase, cathepsin A. Genetic mutations in any of this complex components results in their functional deficiency causing severe lysosomal storage disorders. Here we study the molecular defects underlying sialidosis (mutaions in sialidase; gene NEU1) and galactosialidosis (mutations in cathepsin A; gene PPGB) in the Portuguese population. Methods: Using gDNA extracted from patient’s fibroblasts, we performed a molecular study of the PPGB and NEU1 genes in the known Portuguese patients with galactosialidosis and sialidosis, respectively. The expression of both genes was determined by qRT-PCR. The effect of each mutation was also analysed at protein levels, through different in silico procedures. Results and Conclusions: On the PPGB gene, we identified two predictably deleterious missense mutations (c.394 G>A -Zhou et al, 1996- and c.254 G>T) and two deletions (c.228-229DelC and c.1075-1076DelT), both of them giving origin to transcripts that lead to the synthesis of truncated non-functional proteins. On the NEU1 gene, we found two novel missense mutations associated to a severe form of the disease (c.700 G>A and c.599 C>T), which, at protein levels, lead to the substitution of two aminoacids localized in a surface region of the molecule, already proposed to be involved in the interface of sialidase binding with cathepsin A (Lukong, 2000). Knowledge about these findings is important to allow carrier detection and molecular diagnostics as well as to understand the genetics of LMC.
Arbitragem científica: yes
URI: http://hdl.handle.net/10400.18/780
Appears in Collections:DGH - Posters/abstracts em congressos internacionais

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