Proceedings of the 27th Annual Meeting of the Portuguese Society of Human Genetics (SPGH – Sociedade Portuguesa de Genética Humana) Lisbon, 23 -25 November 2023

Dear colleagues, Dear participants, Dear invited speakers, The Board of Directors of the Portuguese Society of Human Genetics (SPGH) welcomes you to the 27th Annual Meeting, in Lisbon. This year, we are very pleased to be able to continue the biggest event in the area of Human Genetics in Portugal, with a very high number of 300 participants and 114 scientific abstracts submitted. Likewise, the support from companies linked to the sector has been notable. We hope that this year’s scientific program will once again meet your expectations and allow for the much-desired interaction and dialogue between the various professionals in the sector: medical geneticists, researchers, specialists in laboratory genetics, and other professionals with an interest in human genetics. May it once again be a bridge, as suggested by the logo chosen for this meeting, between young and experienced members, between different disciplines of knowledge, and between all those who contribute to the practice of human genetics in this country and in Europe. We would like to thank, from the outset, everyone who contributed and committed themselves to preparing this meeting: the members of the scientific committee, supported by external collaborators, the members of the bioethics committee, the local collaborators who provide the logistics behind the scenes, and the companies whose support is essential to ensure the meeting´s infrastructure. We also owe special thanks to the guest speakers who agreed to come and share their results and scientific advances, and are a decisive element of the annual meeting program. We hope that this annual meeting in Lisbon will be another important milestone in the history of SPGH, and that it will enrich all participants with updated knowledge, new or reinforced professional contacts, and private moments of conviviality. The effective Management of 2023 Peter Jordan José Carlos Ferreira Claudia Oliveira Oral presentations Basic Research OP1 – PERMISSION TO PUBLISH NOT GRANTED BY THE AUTHORS OP2 - DISSECTING THE ROLE OF MICRORNAS IN EFFECTOR VERSUS REGULATORY CD4+ T CELL DIFFERENTIATION DURING (AUTO)IMMUNE RESPONSES IN VIVO Carolina Cunha1, Paula Vargas Romero1, Daniel Inácio1, Ana Teresa Pais1, Catarina Pelicano1, Daniel Sobral2, Marina Costa1, Sofia Mensurado1, Natacha Gonçalves Sousa1, Pedro Papotto1, Francisco Enguita1, Anita Q. Gomes1,3,*, Bruno Silva-Santos1,* 1Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.2Instituto Nacional de Saúde Dr. Ricardo Jorge, Lisboa, Lisbon, Portugal.3H&TRC Health & Technology Research Center, ESTeSL-Escola Superior de Tecnologia da Saúde, Instituto Politécnico de Lisboa, Lisbon, Portugal.*These authors contributed equally Introduction: MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. They have been implicated in the regulation of the differentiation and function of CD4+ T cell subsets, key players in host defense against pathogens, but also responsible for immune-mediated diseases depending on the correct vs incorrect balance, respectively, between pro-inflammatory effector CD4+T cells, including the IFN-γ-producers T helper 1 (Th)1 and the IL-17-producers Th17 cells, and anti-inflammatory regulatory T cells (Treg). While individual miRNAs were found to regulate the differentiation of specific CD4+ T cell populations, an approach based on in vivo responses is still missing and is key to understand how miRNA networks control this balance in pathophysiology. Methodology: We have established a triple reporter mouse for Ifng, Il17 and Foxp3, and subjected it to experimental autoimmune encephalomyelitis (EAE). We performed miRNA-seq analysis on Th1, Th17 and Treg cells isolated from the spleen and lymph nodes (LNs) at peak-plateau stage to identified miRNA candidates specifically expressed in one of the cell populations. We have in vivo modulated their expression levels using antagomiRs and observed the course of EAE progression and characterised their upstream regulation in vitro in either Th1 or Th17 differentiation conditions. Results: The miRNA-seq data has allowed the identification of 110 miRNAs differentially expressed between effector (Th1 and Th17) and regulatory (Treg) subsets. From those, 9 were specifically upregulated in one population versus the others. In vivo miRNA modulation showed that silencing miR-122 precipitated the onset of EAE, whereas overexpressing miR-1247 decreased the severity of the disease. Cytokine-regulated miR-1247 and miR-122 expression levels inversely associated with pathogenic signatures of Th1 and Th17 cells between lymphoid and central nervous systems. Discussion: Our results suggest that miR-122 and miR-1247 act as peripheral brakes to CD4+ T cell pathogenicity that are overruled in the inflamed target organ. These findings may have important implications for autoimmune diseases. OP3 - HE CDH1 REGULATORY BLUEPRINT: SHAPING HEREDITARY DIFFUSE GASTRIC CANCER Celina São José1,2,3, Marta Ferreira1,4, Francisco Almeida1, José Pelaez-Garcia1,3, Ana André1, Janine Senz5, Pardeep Kourah5, Lilian Cordova5, Fiona Puntieri2, Juliane Glasser2, Kasmintan Schrader5, Stefan Mundlos2,6,7, David Huntsman5,8,9, Carla Oliveira1 1Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal2Max Planck Institute for Molecular Genetics, Berlin, Germany.3Doctoral Programme in Biomedicine, Faculty of medicine, University of Porto, Porto, Portugal.4Dept. Computer Science, Faculty of Science, University of Porto.5Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.6Institute of Medical and Human Genetics, Charité Universitätsmedizin Berlin, Berlin, Germany.7Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.8Centre for Translational and Applied Genomics (CTAG), BC Cancer Agency, Vancouver, British Columbia, Canada.9Genetic Pathology Evaluation Centre, University of British Columbia and Vancouver General.10Faculty of Medicine of the University of Porto, Porto, Portugal. Background: Hereditary diffuse gastric cancer (HDGC) is caused by CDH1 or CTNNA1 germline inactivation, which explains <40% of cases. Missing heritability prevents proper management and disease prevention in HDGC-suspected families. We hypothesized that defects in CDH1-regulatory elements contribute to HDGC missing heritability. Methods: We called single-nucleotide/copy-number variants (SNV/CNV) from 19 HDGC probands whole-genome sequencing data, performed gene-ontology analysis, 4C-seq and ATAC-seq in normal stomach epithelia and CRISPR-Cas9, RT-PCR and flow cytometry in cell lines. Results: Besides a MLH1 2,7kb deletion, no relevant coding variants were found in gastrointestinal cancer-associated genes. From stomach ATAC and 4C-seq data, we extracted 46.249 accessible chromatin regions and 370 promoter CDH1 interactor-regions overlapping 1.882 rare CNVs. CNVs overlapping CDH1 promoter interactions revealed a 39 bp-intergenic deletion downstream of CDH1, and a 20kb CDH3 deletion. CRISPR-Cas9 mimicking each deletion (homozygous) triggered 30% and 50% CDH1 mRNA downregulation, respectively for the 39 bp-intergenic and CDH3 CNVs. These sequences acted as enhancers in E-cadherin expressing tissues during development of mouse embryos. The pattern of deleted accessible chromatin regions per patient revealed an HDGC-group bearing downregulated immune-associated pathways. Conclusion: We identified two novel hypomorphic CNVs in CDH1-regulatory regions contributing for CDH1 downregulation, and a MLH1 deletion in a family without classical Lynch Syndrome, that may explain the missing heritability in three HDGC-suspected families. A gastric-specific regulatory element within the MLH1 CNV support predisposition to gastric cancer in this family. Germline CNVs in stomach-specific regulatory regions may predispose to a immune-suppressive phenotype favourable for HDGC development. Grant references: PTDC/BTM-TEC/30164/2017, PTDC/BTM-TEC/6706/2020, 22184, SFRH/BD/140796/2018. OP4 - USING HRDETECT TO TUNE THE CLASSIFICATION OF VARIANTS OF UNCERTAIN SIGNIFICANCE IN A PAN-CANCER COHORT OF 10,675 SAMPLES Orlando P. Rodrigues1,2,3, Lucia Chmelova1,2, Giuseppe Rinaldi1,2, James Whitworth2, Ramsay Bowden2, Helen Davies1,2, Gene Koh1,2, Serena Nik-Zainal1,2 1Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 0XZ, UK.2Academic Department of Medical Genetics, School of Clinical Medicine, University of Cambridge, Cambridge CB2 9NB, UK.3Medical Genetics Department, Hospital Pediátrico e de Introduction: is to the development and of various We – a that data to – be in with to the of variants of in genes. We also the in with variants of We on in and 10,675 within the Genomics In we identified with small variants germline Clinical of variants using Results: Our findings suggest the of as their in to the of we found that all with germline pathogenic and pathogenic variants in high with germline were were Likewise, were with were were Discussion: Our findings the of to While analysis by it the for to the of in In are to from sequencing approach based on While with high we have found with variants at as as the as to is of germline pathogenic variants in may by other the of This the in in Serena on - A A Sofia João and Department of Human Genetics, Porto, Department, Faculty of University of Porto, for the of Science, University of Porto, Porto, Laboratory for and – for the Research and Technology of and and Genetics Department of Human Genetics, Porto, – Health Research and Institute, University of Porto, Portugal. Introduction: The has and the and has interest the to the of In in the and of are the of is are for practice and are in diseases that be by other We have been the and small RNAs to the phenotype of a of diseases caused by Our is to the of the this the in cells and tissues of Methodology: and and the gene in were and in The results at and mRNA levels were by RT-PCR and on will be and the will be by Results: We observed the modulation the of the to the of target the mRNA the of and of to expression to The on and are Discussion: this approach the of specific to as as the of and to a in mRNA levels of the target the for on the of this This is supported by and and Clinical Research OP1 - THE OF DIFFUSE GASTRIC IN CTNNA1 Marta João José P. Kasmintan A Stefan Carla – Instituto de Investigação e Inovação em Saúde, Porto, – Institute of Molecular Pathology and of the University of Porto, of University of Porto, of Science, University of Porto, of Medicine, University of Porto, of Genetics, University of the on – Center for Hereditary University Hospital of Medicine University Hospital and in of University Department of Clinical Genetics, The of Hospital de University of Genetics, of and University of School of Medicine, of Human Genetics, Medical University of Human Genetics, Medical University of Cancer Medical Department Hospital and Institute of Oncology, Genetics Hospital and University Centre, of Genetics, Faculty of Medicine, University of of de Cancer Institute, of Cancer Institute of Oncology, Institute for de de of Laboratory Genetics, Portuguese Institute of Porto, of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, of Molecular Oncology, BC Vancouver, University of Cancer Center, – São Porto, Centre, Health Genetics Cancer Research Center, Cancer of Genetics, Cancer Institute, of Clinical Genetics, Cancer Institute, The of Oncology, Cancer Institute, The de de – Instituto de Molecular e Porto, Germline pathogenic including rare number variants in cancer variants be and to that and and variants be found for all While for is CNV in We hypothesized that pathogenic CNVs in may of the but gastrointestinal The from gastric cancer and cancer CNVs were called with different CNVs from were for their in and by CNVs were using and CNVs were found in in with an A CDH1 deletion, by is found in by it an A deletion in by In an the of the and the of the gene found deleted and supported by by a different for CNVs in associated with a deletion in associated with also by cases. this approach a in at of OP2 - IN A OF Ana João de de Lisboa, de e Instituto de Molecular e Instituto de Investigação e Inovação em Saúde Universidade Porto, Instituto de Investigação e Inovação em Saúde Universidade Porto, de Universidade de – Instituto de Universidade Porto, Porto, Portugal. Introduction: The of sequencing for has the to findings with the of the These are of high and variants in to diseases. the of variants in specific is a in on a this data is for the Portuguese Methodology: We variants in from the of using data from a laboratory which to be of the Portuguese population Results: We identified a of pathogenic or pathogenic variants with an of diseases the with results of the the variants found in to and and The of cancer predisposition and variants in to cancer and and cancer and we also observed variants with and as and the disease Discussion: results suggest that findings be identified in of the Portuguese the of knowledge, this is the findings in These results provide for and in may support the of an to in Portugal. OP3 - A Catarina Marta e Ana de de Lisbon, Introduction: sequencing has a for with a in with This the patient and results we using this Methodology: We performed a analysis of between and 2023 at Medical Genetics to a different patient or with a of Results: performed in of all including in the pathogenic or pathogenic variants were identified in in an of two In were and 1 were for an disease. In new disease were established with have variants in genes. of were found in families. In the including the in of with a versus in a the of in with isolated or one variants in to the of Medical Genetics and Genomics Discussion: Our in other with with of to which in for medical analysis also the and in an in with an on at OP4 - THE Sofia Marta Teresa de e de Lisboa, de Hospital Lisboa, de e de Lisboa, Portugal. Introduction: is the is that a patient with has a of diseases one that explains the of or of one that with as sequencing is associated with of from that of have and of with to Genetics Department to and their and Results: were identified with a or In were with the phenotype and results were as In one as but to be of The for disease were with a that the the without with a phenotype and a of findings In on the were by in and by in and by in and in Conclusion: be a patient with associated with In the to continue data by that be to with This important data that a is one and a have implications in management and proper - THE OF HEREDITARY DIFFUSE GASTRIC CANCER Daniel Ana João Ana Ana João Pedro Ana Peter Pedro Carla – Instituto de Investigação e Inovação em Universidade – Institute of Molecular Pathology and Universidade - Instituto de Universidade of Medicine of the University of e de São for Regenerative Medicine, University School of for and Genetics, Institute for Molecular and of Medicine, e of University of Technology - Instituto de Universidade Introduction: Hereditary Cancer caused by CDH1 of be with of stomach and The number of the of disease we the development of a HDGC with cells to the of target Methodology: We a based on to a which for and This with and were for the of a of HDGC with peripheral cells and were using the Results: We and a the gastric and gastric cell and the gastric We also established and from 9 which were for and stomach The is to be with HDGC Discussion: We a that be in a and a that will allow that no from HDGC to This is a to and in OP1 – IN THE COHORT João Pedro João Carla João Catarina e Ana Sofia Ana de Marta Catarina Sofia Carla de de São Porto, de Investigação e Inovação em Saúde Universidade Porto, Porto, de e Molecular da Universidade Porto, Porto, Universidade Porto, Porto, de Instituto de Porto, Porto, de Instituto de Porto, Porto, de de Hospital de Lisboa, de Hospital e de de de Faculdade de Medicina, Universidade de de Faculdade de Medicina, Universidade de de de Porto, de de e de Hospital de de Instituto de de Francisco de Hospital Dr. de de Hospital Lisboa, de Instituto de de Francisco Lisboa, Portugal. Introduction: cancer is a rare that an to various of This results from pathogenic variants in the which the of target in cell and Methodology: We performed a analysis of and data from with germline variants from Portuguese Results: Our with pathogenic or pathogenic germline of an in a different gene and were from the The 114 1 and with the classical the and established or in the a cancer in with central nervous and the In cancer gastric cancer and were the different germline variants were were and In the the observed by and which for of the families. In the found to be de variants to at an variants this This has of in the Portuguese as a for to understand for with OP2 - OF IN THE Carla João Ana Genetics Hospital e de of Genetics, Faculty of Medicine, University of Center of Genetics Lisbon University Hospital Centre, Genetics Lisbon University Hospital Centre, Genetics São João University Hospital Centre, Hospital and University Centre, Centre, Hospital and University Centre, Hospital and University Centre, of Faculty of Medicine, University of Introduction: The chromatin a in regulation of gene cell and development. The are a of from in that In this and were the to be but other are Methodology: Clinical and of with from based on analysis of medical Results: We from different with to variants in and In two the We and from to at and of with and central nervous of and were in medical were and and Discussion: are a of this the on a of Portuguese associated as and were also found in we a of and as the gene of population to an of their and to and management of on a Clinical OP1 - A IN Ana Ana de de São Porto, de Medicina da Universidade Porto, de de São de de São Introduction: by is responsible for the in whose cell and We a of a with and Clinical to and with family and performed to The to on of to disease. and at on the to disease. showed and with of the has a with and were Molecular of and were to correct Clinical revealed variants in in gene and the of and defects with are in Discussion: The of pathogenic variants in with and by 19 of have been and with the has been This the and of OP2 - OF IN A OF A THE de de Hospital de Lisboa, Introduction: The and for between and downstream including the in cell linked to the variants in have been implicated in different of in isolated and We a patient with and a phenotype with to genetics at to and and of the and the This phenotype with with and of with and and with revealed with and with an and revealed to and variants were identified in and in from a a in gene with an of and variants in of gene have been associated with a of and A patient the but with a of and We with with different variants this all with levels of and were the and with to The severity of phenotype be by the of 1 of three with and new in and with and pathogenic in an individual with A is associated with and associated with variants in and caused by of three with and new OP3 - OF – THE OF e Sousa1, de de Hospital de Lisboa, de da da de Hospital de Lisboa, Portugal. Introduction: within the and and to have been associated with a novel in this is by and within the of with all Methodology: and of two Results: We a to to to at of and at and and interaction bridge, and The revealed diffuse of with no and were and as with and with and a analysis revealed an deletion in analysis of the in the normal The for Discussion: Our family to the of as a Our but from those in the a We the onset of to the of this but as in knowledge, this is the of this OP4 - OF IN THE OF Pedro Carolina de Genetics, de e de de e de Introduction: In Portugal, have an of the is no that of the The for the of at is The of this has allowed the identification of with two in a of cases. of three with no family with disease and with to to and with no of in and differentiation and in the and sequencing performed at data with analysis by Results: In all a pathogenic deletion of gene In the a pathogenic also identified in the gene were This established the of with and and Discussion: In sequencing is the to the of or and the laboratory has to be to the with a We with to the we will on the of that in the in to the for or as as the - IN OF Catarina de Hospital de de Lisboa, Portugal, de de Lisboa, Portugal, da de Lisboa, de Hospital de Lisboa, de Hospital de Lisboa, de Hospital de Lisboa, – de Medicina Introduction: diseases. The Society of Human Genetics has the of and of family members of who experienced Clinical We the of a with no history of disease who to the an during the a by and of the of the the patient a one of the patient and the able to two to the the and revealed The Molecular analysis of a associated with and on the identified variants in and genes. were as variants of the has been in the in The found the of to be an of the by to family members to variants were in the the to be a of the normal on their and with no Discussion: This the of the in the it the of a to and family family members, were for and Basic Research - OF THE IN THE Research for and Health Department of University of Introduction: The a of the has a and and In Portugal, it of their were in Portuguese In we a of from for the and Methodology: A of for the from central and from regions of were for the three and by or sequencing using The of by the analysis of using sequences at were using the with the on the and of in an Results: to the to the and one to the were to the The a of different in the Portuguese We found no by different Discussion: We the in a of of Portuguese to the to results found in other The suggested to have a from the it the The and also found in the Portuguese in from during the in the The analysis a of different in the Portuguese the of different for the in the - OF TO ROLE IN CANCER Juliane de Instituto Nacional de Saúde Ricardo Jorge, Lisboa, and Institute, Universidade de Lisboa, Lisboa, cancer is the and an the two Gene expression of in contribute to disease development. The 1 important in and as a in in this has been as as an In to understand the the of in we have mRNA and levels in different of In have that is in and cancer to the other expression is in in normal we observed that expression is that In this we be an We showed that the of and the for this to This also in a and like and we that target the and observed a expression of in cells with those to cells with control in results that expression levels to be observed in the which the responsible for expression be the of a new to development. - A IN da Pedro Cunha1, Pedro José de Hospital de de Hospital de - de Medicina Molecular We a of a family with a of that found to have two pathogenic variants in The patient to the a of in a for a family history of disease. This patient an with for and two other family members with an at and at to on the patient with the the family who to a to the the patient A including for and performed which revealed a a pathogenic in the gene

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.