Browsing by Issue Date, starting with "2009-09"
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- Gaucher disease in Tunisia: High frequency of the most common mutationsPublication . Cherif, W.; Ben Turkia, H.; Ben Rhouma, F.; Riahi, I.; Chemli, J.; Kefi, R.; Messai, H.; Amaral, O.; Miranda, M.C.; Caillaud, C.; Tebib, N.; Ben Dridi, M.F.; Abdelhak, S.
- Molecular Characterization of Portuguese Patients with Pathologies Related to the Lysosomal Multienzymatic Complex: Sialidosis, Galactosialidosis and GM1 Gangliosidosis.Publication . Coutinho, Maria Francisca; Macedo-Ribeiro, Sandra; Lacerda, Lúcia; Prata, Maria João; Ribeiro, Helena; Baptista, Estela; Rodrigues, M.C.; Alves, SandraThe functional activity of lysosomal enzymes sialidase, beta-galactosidase and N-acetylaminogalacto-6-sulfate in the cell depends on their association in a multienzyme complex with the lysosomal carboxipeptidase, cathepsin A. Mutations in any of these complex components results in their functional deficiency causing severe lysosomal storage disorders. Here we report the molecular defects underlying sialidosis (mutations in sialidase; gene NEU1), galactosialidosis (mutations in cathepsin A; gene PPGB) and GM1 gangliosidosis (mutations in beta-galactosidase; gene GLB1) in the Portuguese population. Methods: Using gDNA extracted from patient’s fibroblasts, we performed a molecular study of the PPGB, NEU1 and GLB1 genes in the biochemically diagnosed Portuguese patients with galactosialidosis, sialidosis and GM1 gangliosidosis, respectively. The expression of these genes was determined by qRT-PCR. The effect of each mutation was evaluated at protein levels using bioinformatic tools. Results: In the PPGB gene, we identified two missense mutations, one novel (p.G85V) and one previously reported (p.V132M) as well as two new deletions (c.228-229delC and c.1075-1076delT) both giving origin to transcripts that lead to the synthesis of truncated non-functional proteins. In the NEU1 gene, we found two novel missense mutations (p.P200L and p.D234N). At protein levels, these mutations result in the substitution of two aminoacids located in a surface region of the molecule, already proposed to be involved in the interface sialidase/cathepsin A. Finally, in the GLB1 gene, we found four different mutations, all of them previously described: one missense mutation (R59H), one nonsense (W527X), one insertion (1572-1577InsG) and one deletion (845-846delC). Interestingly, in the Portuguese population the missense mutation R59H has a higher prevalence among the other ones. This is totally in accordance with which has been described for Brazilian, Iberian and Italian populations. Conclusion: Seven novel mutations are here reported for the first time, which contributes to enrich the knowledge on the mutational spectrum of these diseases and, by extension, to understand better the genetics of the lysosomal multienzymatic complex (LMC). The knowledge of the sialidosis, galactosialidosis and GM1 gangliosidosis mutational spectrum is also an important contribute to a better diagnosis, as well as to allow carrier detection in affected families and prenatal molecular diagnosis, leading to the improvement of genetic counseling with great benefits for the affected families. The existence of a molecular approach to the diagnosis is also of particular important strategy since it helps to overcome the difficulties associated to the neuraminidase enzymatic assay.
- A Função Laboratório de Referência do INSA: reflexão sobre as atribuições, actividades e perspectivas futuras: Dia do INSA 29 de Setembro de 2009Publication . Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
- Common origin of the worldwide-spread mutation c.3503_3504delTC causing the lysosomal storage disease mucolipidosis type IIPublication . Coutinho, Maria Francisca; Encarnação, Marisa; Gomes, Rui; Prata, Maria João; Bargal, Ruth; Filocammo, Mirella; RaasRothschild, A.; Tappino, Barbara; Alves, Sandra
- Tuberculosis in a child - search for the infected adult nearby; case report, Portugal, 2007Publication . Duarte, R.; Tavares, E.; Miranda, A.; Carvalho, A.Tuberculosis (TB) transmission in a non-household setting is difficult to detect, because contact with the source case is often not obvious. Here, we report on a case of a four-year-old child who got infected through sporadic non-household exposure at a coffee shop. The source case was a woman who had suffered from weight loss, productive cough and fatigue for two months before being diagnosed with TB. Screening the child s contacts revealed two active TB cases within its family. Overall 148 contacts were screened for both cases and 18 cases of latent TB infection detected. The connection between the child and the source case, who were not aware of their contact, was confirmed by molecular fingerprinting. Our case report illustrates the difficulty in detecting non-household transmission between individuals that do not have significant contact, and draws attention to the need to look for the infected adult whenever a child falls ill with TB. This report is a reminder of the importance to consider possibly neglected ways of TB transmission and highlights once again the need of early diagnosis of TB.