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

Alejandro J. Brea-Fernández, Miriam Álvarez-Barona, Jorge Amigo, María Tubío-Fungueiriño, Pilar Caamaño, Montserrat Fernández-Prieto, Francisco Barros, Silvia De Rubeis, Joseph Buxbaum, Ángel Carracedo

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageEnglish
Pages (from-to)938-945
Number of pages8
JournalEuropean Journal of Human Genetics
Issue number8
StatePublished - Aug 2022


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