Trio-based exome sequencing reveals a high rate of the de novo variants in intellectual disability.

Autor: Brea-Fernández AJ; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain. a.brea@usc.es., Álvarez-Barona M; Grupo de Medicina Xenómica, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Amigo J; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain.; Fundación Pública Galega de Medicina Xenómica (FPGMX), Santiago de Compostela, Spain., Tubío-Fungueiriño M; Grupo de Medicina Xenómica, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Genomics and Bioinformatics Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Caamaño P; Fundación Pública Galega de Medicina Xenómica (FPGMX), Santiago de Compostela, Spain., Fernández-Prieto M; Genetics Group, GC05, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.; Grupo de Medicina Xenómica, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain., Barros F; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain.; Grupo de Medicina Xenómica, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Fundación Pública Galega de Medicina Xenómica (FPGMX), Santiago de Compostela, Spain., De Rubeis S; Icahn School of Medicine at Mount Sinai, New York, NY, USA., Buxbaum J; Icahn School of Medicine at Mount Sinai, New York, NY, USA., Carracedo Á; Grupo de Medicina Xenómica, Universidade de Santiago de Compostela, Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Santiago de Compostela, Spain.; Grupo de Medicina Xenómica, Fundación Instituto de Investigación Sanitaria de Santiago de Compostela (FIDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.; Fundación Pública Galega de Medicina Xenómica (FPGMX), Santiago de Compostela, Spain.; Genomics and Bioinformatics Group, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain.
Jazyk: angličtina
Zdroj: European journal of human genetics : EJHG [Eur J Hum Genet] 2022 Aug; Vol. 30 (8), pp. 938-945. Date of Electronic Publication: 2022 Mar 23.
DOI: 10.1038/s41431-022-01087-w
Abstrakt: Intellectual disability (ID), a neurodevelopmental disorder affecting 1-3% of the general population, is characterized by limitations in both intellectual function and adaptive skills. The high number of conditions associated with ID underlines its heterogeneous origin and reveals the difficulty of obtaining a rapid and accurate genetic diagnosis. However, the Next Generation Sequencing, and the whole exome sequencing (WES) in particular, has boosted the diagnosis rate associated with ID. In this study, WES performed on 244 trios of patients clinically diagnosed with isolated or syndromic ID and their respective unaffected parents has allowed the identification of the underlying genetic basis of ID in 64 patients, yielding a diagnosis rate of 25.2%. Our results suggest that trio-based WES facilitates ID's genetic diagnosis, particularly in patients who have been extensively waiting for a definitive molecular diagnosis. Moreover, genotypic information from parents provided by trio-based WES enabled the detection of a high percentage (61.5%) of de novo variants inside our cohort. Establishing a quick genetic diagnosis of ID would allow early intervention and better clinical management, thus improving the quality of life of these patients and their families.
(© 2022. The Author(s), under exclusive licence to European Society of Human Genetics.)
Databáze: MEDLINE
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