Análise de achados moleculares relevantes em indivíduos encaminhados para sequenciamento de exoma em clínica de genética de Curitiba PR
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Tipo
TCC
Data de publicação
2024-06-06
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Citações (Scopus)
Autores
Koch, Eduarda Faria Nogueira
Camilotti, Isabela
Camilotti, Isabela
Orientador
Wormsbecker, Liya Regina Mikami
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Introdução: Apesar dos avanços nas técnicas de biologia molecular, muitos pacientes com sintomas complexos e/ou diversos permanecem sem um diagnóstico conclusivo, o que impossibilita a implantação de terapêuticas específicas. Para superar essa barreira, é essencial adotar novas abordagens diagnósticas, como o sequenciamento do exoma. Este exame possibilita a identificação de variantes genéticas que podem estar diretamente relacionadas a condições clínicas específicas, fornecendo uma base mais robusta para o diagnóstico e tratamento, principalmente de doenças raras e pouco conhecidas. Objetivos: Este estudo tem como objetivo avaliar os resultados do sequenciamento do exoma de pacientes com suspeita de doenças genéticas não diagnosticadas em uma clínica especializada em genética em Curitiba, correlacionando variantes genéticas com suas manifestações clínicas. Metodologia: Foi realizada uma análise retrospectiva de 390 prontuários de pacientes que realizaram o sequenciamento de exoma em uma clínica de genética de Curitiba, Paraná, durante o período de 2017 a 2022. Resultados: Dos 390 pacientes, foram identificadas 257 variantes genéticas em 207 genes diferentes. Dentre essas variantes, 24,9% foram classificadas como patogênicas, 21% como provavelmente patogênicas e 54,1% como de significado clínico incerto. Notavelmente, 92 das 144 variantes de significado incerto nunca haviam sido reportadas anteriormente na literatura científica da área associada a quadro clínico. As alterações clínicas mais recorrentes entre os pacientes incluíram disfunções no sistema nervoso, atraso no desenvolvimento global e anormalidades musculoesqueléticas. Aproximadamente 53,3% dos pacientes obtiveram diagnósticos conclusivos que confirmam o diagnóstico clínico. Conclusão: O sequenciamento do exoma provou ser uma ferramenta diagnóstica valiosa, permitindo não apenas a confirmação de diagnósticos genéticos de doenças raras e/ou complexas, mas também facilitando a implementação de estratégias de medicina preventiva, visando minimizar ou prevenir manifestações clínicas adversas.
Introduction: Despite advancements in molecular biology techniques, many patients with complex and/or diverse symptoms remain without a conclusive diagnosis, which hinders the implementation of specific therapies. To overcome this barrier, it is essential to adopt new diagnostic approaches, such as exome sequencing. This test allows the identification of genetic variants that may be directly related to specific clinical conditions, providing a more robust basis for diagnosis and treatment, especially of rare and little-known diseases. Objectives: This study aims to evaluate the results of exome sequencing in patients with suspected undiagnosed genetic diseases in a specialized genetics clinic in Curitiba, correlating genetic variants with their clinical manifestations. Methodology: A retrospective analysis of 390 patient records who underwent exome sequencing at a genetics clinic in Curitiba, Paraná, from 2017 to 2022 was conducted. Results: Among the 390 patients, 257 genetic variants were identified in 207 different genes. Among these variants, 24.9% were classified as pathogenic, 21% as probably pathogenic, and 54.1% as of uncertain clinical significance. Notably, 92 of the 144 variants of uncertain significance had never been previously reported in the scientific literature associated with the clinical condition. The most recurrent clinical alterations among the patients included nervous system dysfunctions, global developmental delay, and musculoskeletal abnormalities. Approximately 53.3% of the patients obtained conclusive diagnoses that confirmed the clinical diagnosis. Conclusion: Exome sequencing proved to be a valuable diagnostic tool, allowing not only the confirmation of genetic diagnoses of rare and/or complex diseases but also facilitating the implementation of preventive medicine strategies, aiming to minimize or prevent adverse clinical manifestations.
Introduction: Despite advancements in molecular biology techniques, many patients with complex and/or diverse symptoms remain without a conclusive diagnosis, which hinders the implementation of specific therapies. To overcome this barrier, it is essential to adopt new diagnostic approaches, such as exome sequencing. This test allows the identification of genetic variants that may be directly related to specific clinical conditions, providing a more robust basis for diagnosis and treatment, especially of rare and little-known diseases. Objectives: This study aims to evaluate the results of exome sequencing in patients with suspected undiagnosed genetic diseases in a specialized genetics clinic in Curitiba, correlating genetic variants with their clinical manifestations. Methodology: A retrospective analysis of 390 patient records who underwent exome sequencing at a genetics clinic in Curitiba, Paraná, from 2017 to 2022 was conducted. Results: Among the 390 patients, 257 genetic variants were identified in 207 different genes. Among these variants, 24.9% were classified as pathogenic, 21% as probably pathogenic, and 54.1% as of uncertain clinical significance. Notably, 92 of the 144 variants of uncertain significance had never been previously reported in the scientific literature associated with the clinical condition. The most recurrent clinical alterations among the patients included nervous system dysfunctions, global developmental delay, and musculoskeletal abnormalities. Approximately 53.3% of the patients obtained conclusive diagnoses that confirmed the clinical diagnosis. Conclusion: Exome sequencing proved to be a valuable diagnostic tool, allowing not only the confirmation of genetic diagnoses of rare and/or complex diseases but also facilitating the implementation of preventive medicine strategies, aiming to minimize or prevent adverse clinical manifestations.
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Palavras-chave
genética , exoma , deficiência intelectual , genetics , exome , intellectual disability