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- WP 9.9 Quality Management Practices, results, suggests, Deliverable D9.1Publication . Pité, Marina; Castanheira, Isabel; Oliveira, Luisa
- Biochemical and molecular heterogeneity in carnitine palmitoyltransferase ii deficiencyPublication . Sousa, Carmen; Fonseca, Helena; Rocha, Hugo; Marcão, Ana; Vilarinho, Laura; Diogo, Luísa; Sequeira, Sílvia; Costa, Cristina; Leão, Elisa; Conceição, Isabel; Gaspar, AnaIntroduction: Carnitine palmitoytransferase II (CPTII) deficiency is a recessively inherited disorder of lipid metabolism. CPT II deficiency has several clinical presentations: the adult form is characterized by episodes of rhabdomyolysis, usually triggered by extensive exercice, cold, fever or prolonged fasting and the infantile-type CPT II hepatocardiomuscular form presents as severe attacks of hypoketotic, hypoglycemia, occasionally associated with cardiac damage. Molecular analysis of CPT II gene allows not only confirmation of classical forms, with typical biochemical abnormalities, but is also key for the diagnosis of less severe forms.The authors will present biochemical and molecular findings of eight CPT II, patients. Material and methods: Acylcarnitine profiles, on dried blood spots, were done as previously reported (Vilarinho et al) Molecular analysis of CPT II gene was done by direct sequencing as reported elsewhere (Finocchiaro et al.). From the eight patients, three were detected through newborn screening and five with clinical symptoms. Results: More pronounced abnormalities in the acylcarnitine profiles are associated with neonatal forms of the disease, while the patients with late onset forms present smother alterations or completely normal profiles. This biochemical heterogeneity correlates well with genetics data. The molecular analysis revealed the presence of ten different mutations, which seven were never reported. Discussion: Our results support that newborn screening can efficiently detect infantile CPT II deficiency but is less effective in detecting adult forms, were biochemical abnormalities may only be present during acute episodes. In these cases accurate clinical characterization alongside with molecular analysis are the key for diagnosis. Bibliography: J.P. Bonnefont, F. et al (2004) Mol. Aspects Med. 25 495–520. Rashed MS, et al.(1995) Diagnosis of inborn errors of metabolism from blood spots by acylcarnitines and amino acids profiling using automated electrospray tandem mass spectrometry. Pediatr Res.38:324–331 Finocchiaro, G. et al (1991). cDNA cloning, sequence analysis, and chomosomal localization of the gene for human carnitinepalmitoyltransferase. Proc. Natl. Acad. Sci. USA 88, 661–665. K. Gempel1 et al. (2002).Screening for Carnitine Palmitoyltransferase II Deficiency by Tandem Mass Spectrometry Anichini A.et al(2011) Genotype-phenotype correlations in a large series of patients with muscle type CPT II deficiency Vilarinho et al. (2009) Four Years of Expanded Newborn Screening in Portugal with MS/MS
- Study of cellular localization of Cystatin B in Unverricht-Lundborg diseasePublication . Duarte, Ana Joana; Ribeiro, Diogo; Chaves, Joao; Amaral, OlgaEpilepsy is a common finding in metabolic diseases and in lysosomal diseases in particular.Unverricht-Lundborg disease (ULD; MIM #601145) is a Progressive Myoclonic Epilepsy caused by mutations in the Cystatin B gene (CSTB) and leading to the impaired action of this intracellular proteinase inhibitor which reversibly binds cathepsins. A unique patient homozygous for mutation p.Q22Q, r.[66g>a,65_66ins66+364pb], which affects normal splicing and gives rise to two cDNA transcripts (normal and abnormal), was recently described. CSTB is ubiquitously expressed, the 98 aminoacid peptide can have nuclear, cytoplasmatic and lysosomal localization. The cellular location varies among different types of cells.
- Pesquisa de Salmonella spp. em águas balnearesPublication . Pizarro, Cristina
- Task 9.1 TDS food listPublication . Dias, M. Graça; Vasco, Elsa
- Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1Publication . Lopes, Alexandra; Aston, Kenneth I.; Thompson, Emma E; Carvalho, Filipa; Gonçalves, João; Huang, N.; Matthiesen, Rune; Noordam, Michiel J.; Quintela, Ines; Ramu, Avinash; Seabra, Catarina; Wilfert, Amy B.; Dai, Juncheng; Downie, Jonathan; Fernandes, Susana; Guo, Xuejiang; Shah, Jiahao; Amorim, Antonio; Barros, Alberto; Carracedo, A.; Hu, Z.; Hurles, M.E.; Moskovtsev, S.; Ober, C.; Paduch, D.A.; Schiffman, J.D.; Schlegel, P.N.; Sousa, M.; Carrell, D.T.; Conrad, D.F.Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man’s risk of disease by 10% (OR 1.10 [1.04–1.16], p,261023), rare X-linked CNVs by 29%, (OR 1.29 [1.11–1.50], p,161023), and rare Y-linked duplications by 88% (OR 1.88 [1.13–3.13], p,0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.261025). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes.
- WP 9.3 Description of kitchen preparations to be used for food cookingPublication . Pité, Marina; Oliveira, Luisa; Castanheira, Isabel