O Estatuto do Embrião

Uma definição universal de embrião é uma tarefa difícil para qualquer ciência exata e impossível em filosofia. Em 1997, afirmava o CNECV: “(...) o embrião não pode deixar de dar origem a um representante da espécie humana, e nunca desembocará num indivíduo de qualquer outra espécie (…) a vida humana merece respeito, qualquer que seja o seu estádio ou fase, devido à sua dignidade essencial. O embrião é, em qualquer fase e desde o início, o suporte físico e biológico indispensável ao desenvolvimento da pessoa humana e nele antecipamos aquilo que há-de vir a ser: não há, pois, razões que nos levem a estabelecer uma escala de respeito.” Sendo o estatuto do embrião um tema ainda tão atual e nunca esgotado, nesta era do genoma humano, qualquer tentativa para o definir poderá parecer incompleta. Como exemplo, veja-se a definição de Keating (1993): “A expressão estatuto do embrião refere-se à questão controversa da proteção moral e jurídica a conceder ao embrião humano em diversos contextos (abortamento, Procriação Medicamente Assistida, experimentação embrionária, etc.), consoante a determinação da sua natureza, que oscila, segundo os casos e as filosofias, entre a de material biológico e a de pessoa (potencial ou não).” Assim, infere-se destes textos que a questão do estatuto do embrião deve ser encarada de modo multidisciplinar e pode ser colocada em diferentes planos – por exemplo, jurídico, que suscitará perguntas como Quais os direitos do embrião? ou ontológico, do tipo O embrião é pessoa? Nesta conferência irão ser apresentados os tipos de estatuto que mais têm sido atribuídos ao embrião: o biológico, o ontológico, o filosófico e o jurídico

Ethical Issues in pre-implantation genetic diagnosis in Portugal: a comparative analysis of professional’s opinions in years 2000 and 2010 using questionnaires

Resumo de poster publicado em revistaMedical genetics has made significant progress in the last decades, especially in the field of prenatal testing. After the dramatic expansion of prenatal diagnosis that started in the seventies, pre-implantation genetic diagnosis (PGD) became a reality in 1990, following advances in the techniques of medically assisted reproduction (MAR). Ethical problems related to this technique start well before the analysis: it is necessary to offer appropriate genetic counselling, to obtain informed consent for the necessary procedures and to maintain strict confidentiality of the whole process. The main ethical problems concern the status of the embryo, the investigation and the manipulation of embryos, eugenic or sex selection and the provision of resources. In 2000 a questionnaire addressing several of the principal ethical concerns, namely the attitude towards PGD, embryos and genetic testing, was distributed to the Directors of the five largest MAR centres in Portugal; in 2010 the same questionnaire was sent to 27 MAR centres and answered by 11. In all cases it was required that the answers should be based on the general policy of each centre. This work presents the comparative analysis of all the obtained data, particularly focusing on the main ethical problems related to this diagnosis, i.e., the status of the human embryo and the attitude of the genetic professionals working in this still relatively new, and very specific, field of genetic diagnosis

Diagnóstico Genético Pré-implantação: aspetos técnicos e considerações éticas

Com o avanço das técnicas de Procriação Medicamente Assistida (PMA), surgiu em 1990 a primeira criança nascida após diagnóstico genético pré-implantação (DGPI). Neste tipo de análise, após estudo feito geralmente entre o terceiro e o quinto dias pós-fertilização, os embriões não afetados são transferidos para o útero materno. O DGPI, apesar de necessitar de técnicas relativamente recentes e dispendiosas, oferece boas perspetivas a casais em risco para determinadas doenças genéticas graves, em alternativa ao diagnóstico pré-natal convencional, particularmente nos casos em que seja necessário realizar PMA – nestes, é mais defensável a seleção embrionária precoce do que uma interrupção de gravidez tardia. Em Portugal, com a Lei n.º 32/2006, relativa à Procriação Medicamente Assistida, posteriormente regulamentada por documento próprio em 2008, todo o procedimento médico e laboratorial ficou mais clarificado, tendo o ordenamento jurídico citado contemplado temáticas fulcrais, como o destino a dar aos embriões excedentários ou em que condições é permitida a investigação embrionária. Os problemas éticos que se colocam no DGPI começam antes da execução do diagnóstico, com o aconselhamento genético, a obtenção do consentimento informado e a estrita manutenção da confidencialidade; todavia, os maiores problemas dizem respeito ao estatuto do embrião humano, à investigação e manipulação de embriões, à seleção de sexo e eugénica e à afetação de recursos. O grande desafio ético das gerações futuras será a definição de limites considerados razoáveis para a correção embrionária de sociedades futuras, nomeadamente através da terapia génica pré-concecional, nunca esquecendo a aplicação dos quatro princípios bioéticos fundamentais: autonomia, beneficência, não-maleficência e justiça

Desenvolvimento de modelos de doenças e de medicamentos a partir de células estaminais pluripotentes induzidas (iPSC): um admirável mundo novo?

info:eu-repo/semantics/publishedVersio

A Novel Frameshift CHD4 Variant Leading to Sifrim-Hitz-Weiss Syndrome in a Proband with a Subclinical Familial t(17;19) and a Large dup(2)(q14.3q21.1)

This article belongs to the Section Molecular Genetics and Genetic Diseases.The genetic complexity of neurodevelopmental disorders (NDD), combined with a heterogeneous clinical presentation, makes accurate assessment of their molecular bases and pathogenic mechanisms challenging. Our purpose is to reveal the pathogenic variant underlying a complex NDD through identification of the "full" spectrum of structural genomic and genetic variants. Therefore, clinical phenotyping and identification of variants by genome and exome sequencing, together with comprehensive assessment of these and affected candidate genes, were carried out. A maternally-inherited familial translocation [t(17;19)(p13.1;p13.3)mat] disrupting the GSG1 like 2 gene (GSG1L2), a 3.2 Mb dup(2)(q14.3q21.1) encompassing the autosomal dominant OMIM phenotype-associated PROC and HS6ST1 gene, and a novel frameshift c.4442del, p.(Gly1481Valfs*21) variant within exon 30 of the Chromodomain helicase DNA binding protein 4 (CHD4) have been identified. Considering the pathogenic potential of each variant and the proband's phenotype, we conclude that this case basically fits the Sifrim-Hitz-Weiss syndrome or CHD4-associated neurodevelopmental phenotype. Finally, our data highlight the need for identification of the "full" spectrum of structural genomic and genetic variants and of reverse comparative phenotyping, including unrelated patients with variants in same genes, for improved genomic healthcare of patients with NDD.If this article is accepted for publication, Open Access publication will be funded by UMIB—Unidade Multidisciplinar de Investigação Biomédica, ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto, Portugal/ITR—Laboratory for Integrative and Trans lational Research in Population Health, Porto, Portugal (https://umib.icbas.up.pt/, accessed on 14 December 2022), both supported by FCT—Fundação para a Ciência e a Tecnologia in the frameworks of UIDP/00215/2020; LA/P/0064/2020. This research was supported by national funds through FCT—Fundação para a Ciência e a Tecnologia, Research Grant HMSP-ICT/0016/2013 of the Harvard Medical School—Portugal Program in Translational Research and Information.info:eu-repo/semantics/publishedVersio

Large interstitial del(13)(q13q14.3): the importance of detailed clinical information in cytogenetic studies

Interstitial deletions of chromosome 13 are known to be associated with retinoblastoma. A wider syndrome may accompany the deletion, including mental retardation and craniofacial dysmorphism. The severity of the phenotype depends on the extent of the deletion. Retinoblastoma is a malignant tumor in the retina and is the most common ocular cancer in children. The association of most cases of retinoblastoma with an interstitial del(13q) has led to the localization of the retinoblastoma gene in 13q14. We report a case of a boy aged 8 referred for cytogenetic studies, presenting with mild mental retardation, craniofacial dysmorphism, delayed intrauterine growth (IUGR) and retinoblastoma. The karyotype was obtained from peripheral blood lymphocyte cultures using high-resolution GTG banding and standard techniques. Fluorescence in situ hybridization was performed using the LSI 13 (RB1) probe (Vysis) for region 13q14 spanning the RB1 gene. The chromosomal analysis revealed a large interstitial deletion of the long arm of chromosome 13. Although the exact breakpoints were difficult to establish, the deleted region did not appear to encompass the band which includes the retinoblastoma gene. Molecular cytogenetic techniques showed that the retinoblastoma gene was deleted. This confirmed the clinical indication of retinoblastoma and defined the deletion breakpoints more precisely. Final karyotype: 46,XY,del(13)(q13q14.3).ish del(13) (q14.1q14.3)(RB1−). Except for the presence of IUGR, the clinical description of this patient is in agreement with other reports in the literature. We would like to emphasize the importance of detailed clinical information that, together with classical and molecular cytogenetic techniques, could be useful in better defining the breakpoints, establishing correct genotype/phenotype correlation and thus providing appropriate genetic counselling. The blood samples of the parents were requested for karyotype analysis in order to clarify this chromosome deletion

A "de novo" inv dup del(6q) - a case report

Abstrat publicado em: Chromosome Research. 2003;21(Suppl 1):S1–S168. doi:10.1007/s10577-013-9364-

A de novo complex chromosome rearrangement (CCR) involving chromosome 5, 6 and 15

Abstrat publicado em: Chromosome Research. 2003;21(Suppl 1):S1–S168. doi:10.1007/s10577-013-9364-

Detection of subtelomeric rearrangements in 1180 patients: FISH and MLPA contribution

Mental retardation (MR) is a major social, educational, and health problem affecting 3% of the population. Subtelomeric chromosome aberrations are one of the major causes of MR with or without multiple anomalies; previous studies have shown that these rearrangements are responsible for 3-6% of unexplained mental retardation. Between 2000-2010 in the Cytogenetics Unit, Centro de Genética Médica Jacinto de Magalhães, INSA (Portugal), the subtelomeric regions of all the chromosomes were analysed in 1180 individuals, whose karyotype had been considered normal. The reasons for referral included (i) psychomotor development delay or (ii) mental retardation with or without dysmorphisms. Until 2007 the analysis of metaphases, obtained from cultured lymphocytes following standard protocols, were performed by "Fluorescence in situ hybridization” (FISH): the first kit to be used was the Chromoprobe Multiprobe-TM (Cytocell) kit (until 2005), which was followed by the TotelVysion Multi-Color FISH Probe (Vysis). In 2007 the "Multiplex Ligation dependent Probe Amplification” (MLPA) was implemented in the laboratory, using kits P036 and P070 (MRC-Holland). All the unbalanced cases detected by MLPA were confirmed by FISH. Of a total of 1180 individuals, 62 (5.3%) showed chromosomal alterations: 60 in the subtelomeric regions and 2 in the control regions. It was not possible to perform any familial studies in 12 of the 62 cases (1.0%) and therefore the results were considered inconclusive. In the other 50 abnormal cases, the parental investigation allowed us to conclude that 30 (2.5%) of these patients had chromosomal abnormalities “de novo” that might be responsible for the clinical phenotype; the remaining 20 possibly abnormal cases (1.7%) were considered polymorphisms without pathological significance, since the apparent deletion or duplication had been inherited from phenotypically normal parents. The authors compare the results obtained in the individuals in the present study with literature reports and highlight the advantages/disadvantages of each technique