1 - Unidade de Genética Médica, Área de Pediatria, Hospital Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central (CHULC), Lisboa, Portugal
2 - Centro de Genética Preditiva e Preventiva (CGPP), Instituto de Biologia Molecular e Celular (IBMC), Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Portugal
- European Society of Human Genetics (ESHG) Conference, 10-13 junho 2023, Glasgow – Escócia
- (Reunião internacional, publicação sob forma de resumo)
Introduction: Clinical exome sequencing (CES) has shown great utility in the diagnosis of genetic disorders. Secondary findings (SFs) are medically actionable variants unrelated to the primary indication for testing, and are a potential consequence of CES with some associated challenges. In order to solve these difficulties, the American College of Medical Genetics and Genomics (ACMG) published the first recommendations for reporting SFs, indicating a list of genes to be evaluated when performing CES in the clinical context. Since then, updates to this list have been published.
Methods: We evaluated the SFs identified in selected patients for CES at our clinical genetics unit, between January 2017 and June 2022. SFs were screened according to ACMG recommendations.
Results: The overall frequency of SF was 2%. 10 unique variants were identified, including 8 pathogenic and 2 likely pathogenic variants, within 8 ACMG-reportable genes. The disease categories of SFs were cardiovascular (60%), cancer (30%) and miscellaneous disease (30%). The SFs results affected the medical management and follow-up strategy in 6 (60%) patients.
Conclusion: To our knowledge, this was the first study investigating SFs in Portugal. We observed that the information of SF from CES could be a valuable and lifesaving effort. On the other hand, it can pose some clinical and ethical difficulties in counselling patients and their families. This study reinforces the need for additional work and consensus in order to support clinical decisions. Additionally, it will be a pioneer for studies in Portuguese population.
Palavras Chave: Whole Exome Sequencing (WES); secondary findings