Browsing by Author "Silva, Maria do Céu"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- Anemia de Fanconi em Portugal: estudo retrospetivo de 34 anos de investigação no INSA (1980-2014)Publication . Ambrósio, Ana Paula; Silva, Maria do Céu; Furtado, José Manuel; Silva, Neuza; Ventura, Catarina; Viegas, Mónica; Correia, HildebertoA Anemia de Fanconi (AF) é uma doença recessiva rara, com uma frequência estimada de 4 a 7 por 1 000 000 de nascimentos. Caraterizase por malformações congénitas, falência medular e hipersensibilidade a agentes clastogénicos de DNA. Devido à grande complexidade desta patologia a primeira abordagem de diagnóstico, consiste na análise da instabilidade cromossómica, após cultura celular com estimulação com agentes clastogénicos diepoxibutano (DEB) ou mitomicina C (MMC). Realizou- se um estudo retrospetivo de 34 anos (1980-2014) em 243 amostras com suspeita de AF e de 25 amostras de familiares de doentes de AF, num total de 268 amostras. Nas 243 amostras suspeitas de Anemia de Fanconi, foram identificadas 37 com AF. A idade média ao diagnóstico foi de 7 anos, existindo um ligeiro predomínio da incidência no sexo feminino (59%). Uma amostra foi classificada como AF(-/+). Nos familiares de doentes com AF foram identificados 2 casos positivos, o que perfaz 39 amostras de AF positivas. Em quatro das amostras AF negativas, observaram-se cariotipos anormais. Estes resultados não permitem estimar uma frequência de doentes de AF em Portugal, uma vez que não englobam indivíduos de todas as regiões portuguesas, mas permitem uma estimativa da frequência espectável.
- Correlation between peripheral cytopenias and cytogenetic changes in the bone marrow in a paediatric population. Experience of 22 yearsPublication . Silva, Maria do Céu; Ambrósio, Ana Paula; Silva, Neuza; Viegas, Mónica; Correia, HildebertoThe haemogram is the most frequent request and an essential tool in the diagnosis of different pathologies in paediatric age, especially in haematological diseases. Peripheral cytopenias is the first laboratory finding suggestive of haematological disease, such as myelodysplastic syndrome, idiopathic thrombocytopenic purpura, among others. Confirmation of these pathologies should include the study of bone marrow, with analysis by different methodologies, including conventional cytogenetic karyotype analysis. In this work, we intend to present and establish a correlation between the results obtained by conventional cytogenetics in bone marrow samples and observation of peripheral cytopenias in a paediatric population over 22 years. A retrospective 22-year series (1995-2017) of 154 bone marrow samples from a paediatric population was analysed, which at the initial diagnosis presented peripheral cytopenia. The samples were process according to the established protocol for chromosome analysis in bone marrow, including cell culture, for each biological product, followed by a cytogenetic study to identify the karyotype. In the 154 samples analysed with peripheral cytopenias, 31 were bicytopenias, 33 pancytopenias, 21 neutropenias, 11 anaemias and 58 thrombocytopenias, of which 22 were of idiopathic origin. We identify 15 samples with abnormal karyotype, some of which presented a complex karyotype. Samples with abnormal karyotypes had pancytopenia or bicytopenia at the same time. Peripheral cytopenias are extremely important for suspicion of paediatric haematological diseases, especially in myelodysplastic syndrome. Conventional cytogenetic analysis of the bone marrow plays a fundamental role in the confirmation of these pathologies, their clinical evolution and the choice of proper therapy, However, micro-arrays should be performed with the aim of identifying micro-deletions / duplications or loss of heterozygosity that are characteristic in this group of pathologies. The author’s don´t have conflict of interest.
- Duplication of the long arm of chromosome 1 in primary myelofibrosis is a malignity factorPublication . Silva, Maria do Céu; Ambrósio, Ana Paula; Marques, Bárbara; Ventura, Catarina; Silva, Elizabeth; Trindade, Maria do Céu; Correia, HildebertoPrimary myelofibrosis (PMF) is one of the Myeloproliferative neoplasms (MPN), which presents a preferential proliferation of megakaryocytes and granulocytes in the bone marrow (BM). One of the causes of morbidity and mortality in PMF is the progression to Acute Myeloid Leukemia (AML). We present a clinical case, of a female individual, 68 years old at the time of the initial diagnosis, who presented moderate anemia and thrombocytosis, and diagnosed as myeloid metaplasia with myelofibrosis. The karyotype performed in the BM, resulted in a duplication of the long arm of chromosome 1, del(1)(q21q32). The patient remained stable and without therapy for 5 years having performed a myelogram at this time, and a bone biopsy that showed an advanced myelofibrosis. In parallel, cytogenetic studies and search for V617F mutation in the Jak2 gene, indicated the absence of the mutation V617F, and confirmed the presence of the dup(1)(q21q32). the patient started therapy with an erythropoietin substitute. Currently, with 8 years of evolution of the disease, she has no clinical complaints, without transfusions and maintaining therapy. The dup(1)(q21q32) associated with MPN is a rare anomaly and is associated with AML evolution. Since the patient understudy did not evolve to AML, FISH, and high-resolution microarray studies were performed. The studies confirmed the observed breacpoints and did not show other changes Based on the patient's clinical history and results, we suggest that the dup(1)(q21q32) alone does not induce an evolution to AML and that the duplication of genes correlated with this pathology (ex: ARNT, among others) is not a sufficient factor for the development of a more aggressive progression. However, more studies should be carried out in order to clarify the role of this alteration in NM.
- Fanconi's anemia - Retrospective study over a period of 37 yearsPublication . Ambrósio, Ana Paula; Silva, Maria do Céu; Silva, Neuza; Viegas, Mónica; Furtado, José; Correia, HildebertoFanconi anemia (FA) is a rare disease, with an estimated frequency of 1 to 5 per 1,000,000 births, which may increase in some ethnic group (like Ashkenazi Jewish and Gypsy). It’s an autosomal recessive disease that may have an X-linked transmission. Patients with FA may have congenital malformations, bone marrow failure, hypersensitivity to clastogenic agents, chromosomal fragility, and increased susceptibility to oncological diseases. Due to the great complexity of this pathology, the first approach to diagnosis consists of the detection of chromosomal aberrations (breaks, structural rearrangements, rings) in peripheral blood cells in culture with clastogenic agent such as diepoxybutane (DEB) or mitomycin C (MMC). We intend to present the results of chromosome instability studies induced by DEB and MMC performed in our institution. A retrospective 37 years series (1980-2017) of 274 samples sent to the cytogenetic laboratory with suspicion of FA and 28 samples of relatives of patients with FA were perform. The samples were process according with the protocol established by the International Fanconi Anemia Registry (IFAR). In the 274 analysed samples, 39 cases with AF were identify. In the cytogenetic studies of relatives with AF, 2 positive cases were identified for FA. Abnormal karyotypes were also observed in 8 samples suspected of AF. In this study, 41 new cases of AF were identify, mainly from the Lisbon and Tagus Valley regions and some specific cases from Azores, the central region and from the Portuguese speaking African countries (PALOP). This study evidences that the majority of the presented cases are underdiagnosed. These results do not allow to estimate a frequency of patients with AF in Portugal, since it does not include individuals from all Portuguese regions, and are include two individuals of PALOP origin. It would be interesting to carry out Next generation sequencing on the Fanconi positive samples in order to obtain in a single assay the analysis of the various genes involved in the pathology thus identifying the genetic change causing the disease. The authors have no conflict of interest.
- Perda do cromossoma Y versus doenças hematológicas malignasPublication . Silva, Maria do Céu; Ambrósio, Ana Paula; Furtado, José; Correia, HildebertoA associação clínica entre a perda do cromossoma Y (PY) e as doenças hematológicas malignas é um tema controverso, uma vez que ambos os acontecimentos estão correlacionados com o envelhecimento. Tendo como objetivo, tentar obter uma correlação entre a perda do cromossoma Y e as diferentes doenças hematológicas malignas, procedeu-se a um estudo retrospetivo de 15 anos, dos resultados citogenéticos de 1241 indivíduos do sexo masculino identificados como portadores de uma doença hematológica maligna. Dos 1241 indivíduos analisados 78, (6,3%) apresentavam a perda do cromossoma Y. Dos 78 indivíduos que apresentavam perda do cromossoma Y, 18 (23%); 2 (2,6); 13 (16,6%); 10 12,8%); 31 (39,7%) e 4 (5,1%) estavam incluídos, respetivamente, nos grupos de Neoplasmas Mieloproliferativos (NM), Neoplasma Mielodisplásico/ Mieloproliferavo (SMD/NM), Síndrome Mielodisplásico (SMD), Leucemias Mieloides Agudas (LMA), Neoplasmas de Células B (NB) e Neoplasmas de Células T (NT). Pela mesma ordem a média de idades destes indivíduos foram: 65; 72; 73; 47; 71; 65. Não foram identificadas PY em indivíduos incluídos nos grupos de Leucemias Agudas de Linhagem Ambígua (LALA), Leucemias Linfoblásticas Agudas de Linhagem B ou T (LLB ou LLT) e Linfomas de Hodgkin. Quando para cada grupo se identificam as diferentes patologias, os valores poderão ser diferentes, realçando - se no grupo dos NM a patologia Leucemia Mielóide Crónica (LMC). Neste caso específico, 9 dos 18 indivíduos incluídos no grupo NM com PY, estão diagnosticados como LMC e a média de idades é próxima da estabelecida na bibliografia (5ª- 6ª década de vida) para esta patologia. O que sugere que a perda do Y neste caso, não seja um acontecimento dependente da idade, mas um fenómeno relacionado com a patologia. Existem 25 (32,1%) doentes em que para além da perda do cromossoma Y foi identificada outra anomalia citogenética associada. Existem poucos estudos que evidenciam a correlação entre a perda do cromossoma Y e as doenças hematológicas malignas, uma vez que são acontecimentos associados ao envelhecimento, contudo o nosso estudo mostra que a perda do cromossoma Y, poderá ser um fator a ter em consideração em algumas das doenças hematológicas malignas.
- A retrospective study of Down syndrome in prenatal diagnosis. Did chorionic villus sampling allow a better prevention?Publication . Simão, Laurentino; Silva, Marisa; Brito, Filomena; Alves, Cristina; Marques, Bárbara; Ferreira, Cristina; Ambrósio, Paula; Silva, Maria do Céu; Ventura, Catarina; Duarte, Guida; Caetano, Paula; Correia, Joaquim; Melo, AntonietaIntroduction Down syndrome (DS) is the most common single genetic cause of human moderate mental retardation, with an estimated prevalence of 9.2 cases per 10,000 live births. We aimed at analyzing changes in prenatal diagnosis (PND) over time, namely the referral reasons for chromosome analyses and the introduction of chorionic villus sampling (CVS), and its influence on the results obtained in DS cases. Methods We retrospectively evaluated the PND results from samples analyzed between 1987 and 2011 (25 years) in our cytogenetic laboratory taking into account the referral reasons, type of sample, karyotype and reporting time. Results 263 fetuses with a karyotype compatible with DS were identified in a total of 18,107 karyotypes (1.5%). The highest frequencies of DS were found among cases referred because of ultrasonography findigs (namely increased nuchal translucency) or positive first trimester screening and when one parent carries a chromosomal rearrangement. The frequency of recurrence was found to be 1/72. The increasing use of CVS led to an earlier response in terms of gestational age (mean at diagnosis- 13+4 weeks). In addition, an increased percentage of karyotypes with SD was detected (8.4% of CVS samples). On the other hand, implementation of molecular rapid aneuploidy detection in part of the samples allowed a better report time in DS cases, from 23 days in 1987 to 2 days in 2011. Discussion DS detection remains the most important reason for performing PND. The collecting of CVS has been rising over the last years, which has resulted in an increased number of trisomy 21 cases identified in a lower gestational age, allowing a better karyotype-phenotype correlation in earlier pregnancies. Moreover, the use of complementary molecular techniques for the detection of common aneuploidies reduced the mean reporting time and allowed an earlier decision of the couple concerning the future of gestation.