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

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...

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Bibliographic Details
Published in:European journal of human genetics : EJHG 2022-08, Vol.30 (8), p.938-945
Main Authors: Brea-Fernández, Alejandro J, Álvarez-Barona, Miriam, Amigo, Jorge, Tubío-Fungueiriño, María, Caamaño, Pilar, Fernández-Prieto, Montserrat, Barros, Francisco, De Rubeis, Silvia, Buxbaum, Joseph, Carracedo, Ángel
Format: Article
Language:English
Subjects:
Diagnosis
Exome
Exome Sequencing
Genetic screening
Humans
Intellectual disabilities
Intellectual Disability - diagnosis
Intellectual Disability - genetics
Neurodevelopmental disorders
Neurodevelopmental Disorders - genetics
Next-generation sequencing
Patients
Quality of Life
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Summary: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.
ISSN:1018-4813
1476-5438
DOI:10.1038/s41431-022-01087-w