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As perturbações do neurodesenvolvimento são um conjunto de perturbações que comprometem a função neurocognitiva. Entre as manifestações mais prevalentes encontram- se o atraso no desenvolvimento e o défice intelectual, geralmente diagnosticadas durante a infância ou adolescência , com uma prevalência de 1-3% em crianças a nível global. Os testes genéticos são parte do protocolo padrão nos cuidados de várias perturbações do desenvolvimento neurológico e a sua utilização tem sido cada vez mais frequente. Este projeto tem como objetivo o diagnóstico molecular em amostras de sangue total de doentes pediátricos com um quadro clínico de perturbação do desenvolvimento intelectual, utilizando sequenciação de nova geração. Foram analisadas 18 amostras de DNA, através de sequenciação de exoma completo . As variantes identificadas foram validadas por reação em cadeia da polimerase e sequenciação de Sanger. Utilizando um painel de genes para perturbações do desenvolvimento intelectual, foram identificadas variantes em 10 dos 18 casos , correspondendo a um rendimento diagnóstico de 12%. Apenas uma variante patogénica foi identificada, tendo sido também detetados dois casos com múltiplas variantes. No entanto, na maior parte dos casos foram identificadas apenas variantes de significado clínico incerto. Estes resultados refletem a elevada complexidade e heterogeneidade genética das perturbações do neurodesenvolvimento e os desafios associados à classificação e interpretação clínica das variantes.
Neurodevelopmental disorders are a group of disorders that impair neurocognitive function. Among the most prevalent manifestations are developmental delay and intellectual disability, typically occurring during childhood or adolescence, with a prevalence of 1- 3% in children globally. Genetic testing ispart of the standard protocol in the care of several neurodevelopmental disorders and its use has become increasingly frequent. This project aims to perform molecular diagnosis in whole blood samples from pediatric patients with clinical symptoms of intellectual developmental disorder, using next -generation sequencing. Eighteen DNA samples were analyzed through whole -exome sequencing. The identified variants were validated by polymerase chain reaction and Sanger sequencing. Using a gene panel for intellectual developmental disorders, variants were identified in 10 of the 18 cases, corresponding to a diagnostic yield of 12%. Only one pathogenic variant was identified, and two cases with multiple variants were also detected. However, in most cases, only variants ofu ncertain clinical significance were identified. These results reflect the high complexity and genetic heterogeneity of neurodevelopmental disorders, and the challenges associated with the classification and clinical interpretation of variants.
Neurodevelopmental disorders are a group of disorders that impair neurocognitive function. Among the most prevalent manifestations are developmental delay and intellectual disability, typically occurring during childhood or adolescence, with a prevalence of 1- 3% in children globally. Genetic testing ispart of the standard protocol in the care of several neurodevelopmental disorders and its use has become increasingly frequent. This project aims to perform molecular diagnosis in whole blood samples from pediatric patients with clinical symptoms of intellectual developmental disorder, using next -generation sequencing. Eighteen DNA samples were analyzed through whole -exome sequencing. The identified variants were validated by polymerase chain reaction and Sanger sequencing. Using a gene panel for intellectual developmental disorders, variants were identified in 10 of the 18 cases, corresponding to a diagnostic yield of 12%. Only one pathogenic variant was identified, and two cases with multiple variants were also detected. However, in most cases, only variants ofu ncertain clinical significance were identified. These results reflect the high complexity and genetic heterogeneity of neurodevelopmental disorders, and the challenges associated with the classification and clinical interpretation of variants.
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Perturbações do neurodesenvolvimento NGS Disgnóstico molecular Variantes genéticas Défice intelectual