Percorrer por autor "Carreiro, Helena"
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- Cancro da mama hereditário: dupla heterozigotia para variantes patogénicas nos genes BRCA1 e ATMPublication . Theisen, Patrícia; Rodrigues, Pedro; Silva, Catarina; Ribeiro, Leonor; Carreiro, Helena; Gervásio, Helena; Vieira, Luís; Gonçalves, JoãoIntrodução/objetivos: O cancro da mama hereditário (CMH) representa 5-10% dos casos de cancro da mama, destes ~30% devem-se a variantes patogénicas germinativas nos genes BRCA1 e BRCA2. Vários outros genes de suscetibilidade para CMH têm sido identificados, com diferentes graus de penetrância. A determinação da causa genética subjacente ao CMH permite identificar os indivíduos com risco aumentado de desenvolver tumores, os quais podem beneficiar de medicina personalizada, e também oferecer o teste genético preditivo a familiares em 1º grau, após aconselhamento genético. A sequenciação de nova geração (NGS) veio revolucionar o diagnóstico molecular do CMH proporcionando alta eficiência e baixos custos, usando painéis multigénicos. Neste trabalho, utilizou-se a NGS para sequenciar um painel de genes de suscetibilidade para CMH numa doente com história pessoal de cancro da mama e ovário e história familiar de cancro do lado materno e paterno. Métodos: NGS com preparação das bibliotecas de sequências-alvo a partir de DNA genómico (protocolo Trusight Cancer - TruSight Rapid Capture, Illumina) e sequenciação no MiSeq (Illumina). Análise bioinformática efetuada com os programas MiSeq Reporter, Enrichment e Variant Studio (Illumina), Alamut Visual e Integrative Genomics Viewer. As variantes patogénicas identificadas por NGS nos genes BRCA1 e ATM foram confirmadas por sequenciação de Sanger. Resultados: Foi identificado um caso raro de dupla heterozigotia para as variantes patogénicas BRCA1: c.2037delinsCC, p.(Lys679Asn*4) e ATM: c.3802delG, p.(Val1268*). A pesquisa destas variantes num familiar com cancro da mama e em dois familiares em 1º grau saudáveis, após aconselhamento genético, permitiu diagnosticá-los como portadores de uma ou de ambas as variantes. Conclusões: A NGS de um painel de genes de suscetibilidade para CMH permitiu identificar um caso raro de dupla heterozigotia para variantes patogénicas nos genes BRCA1 e ATM. Esta abordagem analítica foi crucial pois possibilitou um aconselhamento genético orientado em função das variantes identificadas e do risco de desenvolvimento de tumores associados a uma ou a ambas as variantes. Este caso demonstra a vantagem da sequenciação de um painel multigénico face à análise molecular limitada aos genes BRCA1 e BRCA2.
- CMV and HCV infections in HIV/non-HIV mothers and newborns: prevalence, frequency and risk factorsPublication . Lopo, Sílvia; Pereira, Maria Amável; Mendonça, Joana; Vinagre, Elsa; Reis, Tânia; Cordeiro, Dora; Almeida, Catarina; Água-Doce, Ivone; Manita, Carla; Palminha, Paula; Pádua, Elizabeth; Paixão, Maria Teresa; Carreiro, Helena; Barroso, Rosalina; Campos, Teresa; Marques, TâniaThe incidence of HIV infections in gestational age is an important Public Health issue as are concerns about co-infection with opportunistic viruses, such as CMV/HCV. Several authors refer higher ratios of congenital CMV infection in children born to HIV infected mother than in uninfected. In the case of HCV, perinatal transmission increases in cases of mothers co-infected with HIV. Aims:To study CMV/HCV infection/co-infection in HIV/non-HIV women and their newborns between 2006-2010, according to epidemiological, laboratory and clinical data; to evaluate frequency of CMV/HIV/HCV maternal-fetal transmission and analyse risk factors for infections. Methods:Plasma and/or urine of 137 HIV and 140 non-HIV women, attending a Lisbon Hospital and their 140 newborns were analysed at NIH. HIV-1 and/or HIV-2 proviral DNA nested-PCR was performed on HIV mothers and their newborn’s plasma. Maternal plasma was screened for CMV and HCV antibodies; RNA determination, genotyping and viral load were performed on women with HCV antibodies, their newborn’s plasma was also screened for HCV. Newborn’s urine was inoculated for CMV detection. Data analysis was performed using SPSS 17.0 and Fisher's exact test. Results:HIV1 vertical transmission was diagnosed in 3/140(2.1%) cases. CMV congenital infection was diagnosed in 4(2.9%) newborns from HIV women and no congenital CMV infection was diagnosed in newborns from non-HIV women. 2/137(1.5%) HIV women and 14/140(10.0%) non-HIV women were CMV seronegative. HCV infection was detected in 6(4.4%) HIV women; all had HCV positive viral load; different genotypes were found. One case of HCV perinatal transmission was diagnosed. No HCV antibodies were found in non-HIV women. No children were HIV/HCV or CMV/HCV coinfected but 2 were HIV/CMV coinfected. There is evidence of significant statistical associations with race/ethnicity and time of pregnancy. Conclusion:In this study HIV women had higher CMV/HCV antibody prevalence and frequency of maternal-fetal transmission than non-HIV women. 2/137 HIV seronegative newborns and 2/3 HIV newborns were CMV congenitally infected; this difference should be further studied, as the consequences of CMV/HCV infections may become increasingly serious and complex in the presence of HIV. This specific group is not representative of the Portuguese infected women, nevertheless the significant risk factors found and other risk factors studied without strong associations should be considered in larger studies.
- Hereditary breast and ovarian cancer: two cases of double heterozigosity for pathogenic variants in the BRCA1 or BRCA2 and ATM genesPublication . Theisen, Patrícia; Rodrigues, Pedro; Silva, Catarina; Carpinteiro, Dina; Ribeiro, L.; Carreiro, Helena; Gervásio, H.; Leal da Silva, José; Vieira, Luís; Gonçalves, JoãoIntroduction: Hereditary breast and ovarian cancer (HBOC) is estimated to represent 5-10% of all breast and ovarian cancer cases. Pathogenic germline variants in BRCA1 and BRCA2 account for 25% of familial cases. The identification of genetic defects in HBOC patients allows detection of carriers that can benefit from cancer risk management protocols, and predictive genetic testing to at-risk family members, after appropriate genetic counseling. Two female patients with a personal and family history of cancer were studied by next-generation sequencing (NGS). Methods: NGS using TruSight Cancer Panel (Illumina) followed by bioinformatic analysis of 18 genes associated with HBOC was performed. Pathogenic variants were confirmed by Sanger sequencing. Results: A rare event of double heterozigosity for pathogenic variants was identified in both patients: patient A was heterozygous for BRCA1:c.2037delinsCC, p.(Lys679Asn*4) and ATM:c.3802delG, p.(Val1268*) and patient B carried both BRCA2:c.6001dupT, p.(Ser2001Phefs*2) and ATM:3435_3436delTGinsA, p.(Asp1145Glufs*11). After genetic counseling, three relatives of patient A were analyzed: while one of her two healthy sons was heterozygous for the ATM variant, the other was a double heterozygote for BRCA1:c.2037delinsCC and ATM:c.3802delG; a female cousin, recently diagnosed with breast cancer, was a carrier of ATM:c.3802delG only. Conclusions: The identification of these two rare cases of double heterozigosity for pathogenic variants in BRCA1/BRCA2 and ATM genes, highlights the importance of using NGS-gene panel testing in HBOC. If molecular analysis had been restricted to BRCA genes only, the pathogenic ATM variants would have been missed in both families, depriving them of appropriate genetic counseling and cancer risk management.