Browsing by Author "Rebelo, O"
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- Amplified and Homozygously Deleted Genes in Glioblastoma: Impact on Gene Expression LevelsPublication . Crespo, I; Tão, H; Nieto, AB; Rebelo, O; Domingos, P; Vital, AL; Patino, MC; Barbosa, MD; Lopes, MC; Resende de Oliveira, C; Orfão, A; Tabernero, MDBACKGROUND: Glioblastoma multiforme (GBM) displays multiple amplicons and homozygous deletions that involve relevant pathogenic genes and other genes whose role remains unknown. METHODOLOGY: Single-nucleotide polymorphism (SNP)-arrays were used to determine the frequency of recurrent amplicons and homozygous deletions in GBM (n = 46), and to evaluate the impact of copy number alterations (CNA) on mRNA levels of the genes involved. PRINCIPAL FINDINGS: Recurrent amplicons were detected for chromosomes 7 (50%), 12 (22%), 1 (11%), 4 (9%), 11 (4%), and 17 (4%), whereas homozygous deletions involved chromosomes 9p21 (52%) and 10q (22%). Most genes that displayed a high correlation between DNA CNA and mRNA levels were coded in the amplified chromosomes. For some amplicons the impact of DNA CNA on mRNA expression was restricted to a single gene (e.g., EGFR at 7p11.2), while for others it involved multiple genes (e.g., 11 and 5 genes at 12q14.1-q15 and 4q12, respectively). Despite homozygous del(9p21) and del(10q23.31) included multiple genes, association between these DNA CNA and RNA expression was restricted to the MTAP gene. CONCLUSIONS: Overall, our results showed a high frequency of amplicons and homozygous deletions in GBM with variable impact on the expression of the genes involved, and they contributed to the identification of other potentially relevant genes.
- Choroid plexus tumours: a surgically treated seriesPublication . Barbosa, MD; Rebelo, O; Barbosa, P; Lacerda, A; Fernandes, RChoroid plexus tumours-carcinomas and papillomas are rare, especially in adults, and they pose some problems in their diagnosis and management. We have reviewed a series of nine cases from our institution surgically treated during the last 18 years. Their clinical charts, neuroradiological examinations, surgical technique, neuropathology and follow-up were analysed. In only one case total removal proved to be impossible, but even in cases of total removal recurrence appeared in two cases (one carcinoma and one papilloma). Morbility is especially associated with posterior fossa tumours. These rare tumours are managed surgically. They are usually associated with hydrocephalus, and it is difficult to forecast whether or not permanent CSF drainage will be required. A long-term follow-up is needed in patients with this type of tumour.
- Creutzfeldt-Jakob disease: typical imaging findingsPublication . Felix-Morais, R; Andrade, LC; Rebelo, O
- Cystic intraventricular schwannoma: case report and review of the literaturePublication . Barbosa, MD; Rebelo, O; Barbosa, P; Gonçalves, J; Fernandes, RIntraventricular schwannoma is an exceedingly rare tumour with only 6 cases described in the literature. One case of a cystic intraventricular schwannoma operated on at our Institution is analyzed and the other cases reported in the literature are reviewed. Complete removal was achieved and no recurrence was noted after a follow-up period of 10 years. Intraventricular schwannomas are rare tumours that are amenable to complete surgical removal, having a good prognosis without the need of adjuvant therapy.
- Intratumoral patterns of clonal evolution in gliomasPublication . Vital, AL; Tabernero, MD; Crespo, I; Rebelo, O; Tão, H; Gomes, F; Lopes, MC; Orfão, AFew studies have explored the patterns of clonal evolution in gliomas. Here, we investigate the cytogenetic patterns of intratumoral clonal evolution of gliomas and their impact on tumor histopathology and patient survival. Cytogenetic analysis of 90 gliomas was performed in individual tumor cells (>200 cells/tumor) using multicolor (N = 16 probes) interphase-FISH. Overall, chromosome gains were more frequent than chromosome losses. Gains of chromosome 7 and/or EGFR amplification were detected in 91% of the cases, whereas del(9p21) (77%) and del(10q23) (78%) were the most frequent chromosome losses. Virtually, all cases (99%) showed >/=2 tumor cell clones, with higher numbers among high- versus low-grade gliomas (p = 0.001). Nine different cytogenetic patterns were found in the ancestral tumor clones. In most gliomas, ancestral clones showed abnormalities of chromosome 7, 9p, and/or 10q and cytogenetic evolution consisted of acquisition of additional abnormalities followed by tetraploidization. Conversely, early tetraploidization was associated with low-grade astrocytomas-2/3 pilocytic and 3/6 grade II diffuse astrocytomas-and combined loss of 1p36/19q13 with oligodendrogliomas, respectively; both aberrations were associated with a better patient outcome (p = 0.03). Overall, our results support the existence of different pathways of intratumoral evolution in gliomas.
- Intraventricular LesionPublication . Bastos-Lima, P; Marques, C; Cabrita, F; Barbosa, MD; Rebelo, O; Rio, F
- Limb-girdle muscular dystrophy in a Portuguese patient caused by a mutation in the telethonin genePublication . Negrão, L; Matos, A; Geraldo, A; Rebelo, OLimb-girdle muscular dystrophy 2G is caused by mutations in the telethonin (TCAP) gene in chromosome 17q11-12. This rare form of hereditary muscle disease was originally described in Brazilian patients and was recently identified in Chinese and Moldavian patients. We present the first Portuguese patient with a limb-girdle muscular dystrophy caused by a mutation in the TCAP gene. A Caucasian male, 50 years old, presented in his early twenties, slowly progressive weakness in upper and lower limbs. Neurologic examination revealed severe atrophy and weakness in the muscles of the arms, thighs and legs' anterior compartment. Muscle MRI of the thighs and legs revealed severe atrophy of all the muscles of the thighs and legs' anterolateral compartment, in a symmetrical way. Molecular studies identified the homozygous c.157C > T (p.Gln53X) mutation in exon 2 of the TCAP gene, already described in Brazilian patients.
- Phenotyping GABA transaminase deficiency: a case description and literature reviewPublication . Louro, P; Ramos, L; Robalo, C; Cancelinha, C; Dinis, A; Veiga, R; Pina, R; Rebelo, O; Pop, A; Diogo, L; Salomons, GS; Garcia, PGamma-aminobutyric acid transaminase (GABA-T) deficiency is an autosomal recessive disorder reported in only three unrelated families. It is caused by mutations in the ABAT gene, which encodes 4-aminobutyrate transaminase, an enzyme of GABA catabolism and mitochondrial nucleoside salvage. We report the case of a boy, deceased at 12 months of age, with early-onset epileptic encephalopathy, severe psychomotor retardation, hypotonia, lower-limb hyporeflexia, central hypoventilation, and rapid increase in weight and, to a lesser rate, length and head circumference. He presented signs of premature pubarche, thermal instability, and water-electrolyte imbalance. Serum total testosterone was elevated (43.3 ng/dl; normal range <16), as well as serum growth hormone (7.7 ng/ml; normal range <1). Brain magnetic resonance imaging (MRI) showed decreased myelination and generalized brain atrophy, later confirmed by post-mortem examination. ABAT gene sequencing was performed post-mortem, identifying a homozygous variant c.888G > T (p.Gln296His),not previously described. In vitro analysis concluded that this variant is pathogenic. The clinical features of this patient are similar to those reported so far in GABA-T deficiency. However, distinct mutations may have a different effect on enzymatic activity, which potentially could lead to a variable clinical outcome. Clinical investigation aiming for a diagnosis should not end with the patient's death, as it may allow a more precise genetic counselling for the family.
- Síndroma de Cushing ACTH-dependente: estudo retrospectivoPublication . Paiva, I; Ribeiro, C; Gomes, L; Baptista, C; Gomes, F; Rito, M; Rebelo, O; Marnoto, D; Moura, C; Leitão, F; Carvalheiro, MAIM: To evaluate the characteristics and outcomes of the patients diagnosed as ACTH-dependent Cushing syndrome, registered in the department. MATERIAL AND METHODS: We reviewed the files of forty-three patients followed from 1974 to 2002. RESULTS: A progressive rise in the number of patients diagnosed was found, being 80% females. Clinical suspicion was based mostly on the typical fat distribution; hirsutism and amenorrhoea were important in women. The more reliable diagnostic tests were: 11 pm cortisol, day curve of ACTH and cortisol, and dexamethasone suppression tests. The ACTH response to CRH during inferior petrosal sinus sampling permitted the diagnosis of ectopic source. In thirty-seven patients a pituitary adenoma was diagnosed. The three patients diagnosed before 1985 went for bilateral adrenalectomy (Nelson's syndrome in two); the others were submitted to transsphenoidal pituitary adenomectomy, obtaining remission in twenty six at the first operation and in two others at the second. Three patients had a recidive. Of the six patients with persistent disease (all treated with metyrapone or ketoconazole), three were submitted to radiotherapy, two to bilateral adrenalectomy, and one was waiting for surgery. Four patients had a bronchial carcinoid, successfully removed in three. One patient was lost to follow-up and another was still being evaluated. CONCLUSIONS: We found a positive evolution in the capacity to diagnose and treat these patients. Neurosurgical ability to achieve remission was 80% in the operated cases. More effective technical methods and drugs, as well as a multidisciplinary and dedicated medical team, lead to long lasting remissions in most of the patients.