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Genetic factors contributing to autism spectrum disorder in Williams-Beuren syndrome

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dc.contributor.author Codina i Solà, Marta, 1988-
dc.contributor.author Costa-Roger, Mar
dc.contributor.author Pérez García, Débora, 1985-
dc.contributor.author Flores Peirats, Raquel
dc.contributor.author Palacios Verdú, María Gabriela, 1983-
dc.contributor.author Cuscó Martí, Ivon, 1973-
dc.contributor.author Pérez Jurado, Luis Alberto
dc.date.accessioned 2020-02-14T08:24:55Z
dc.date.available 2020-02-14T08:24:55Z
dc.date.issued 2019
dc.identifier.citation Codina-Sola M, Costa-Roger M, Pérez-García D, Flores R, Palacios-Verdú MG, Cusco I. et al. Genetic factors contributing to autism spectrum disorder in Williams-Beuren syndrome. J Med Genet. 2019 Dec;56(12):801-8. DOI: 10.1136/jmedgenet-2019-106080
dc.identifier.issn 0022-2593
dc.identifier.uri http://hdl.handle.net/10230/43599
dc.description.abstract Background: The hallmark of the neurobehavioural phenotype of Williams-Beuren syndrome (WBS) is increased sociability and relatively preserved language skills, often described as opposite to autism spectrum disorders (ASD). However, the prevalence of ASD in WBS is 6-10 times higher than in the general population. We have investigated the genetic factors that could contribute to the ASD phenotype in individuals with WBS. Methods: We studied four males and four females with WBS and a confirmed diagnosis of ASD by the Autism Diagnostic Interview-Revised. We performed a detailed molecular characterisation of the deletion and searched for genomic variants using exome sequencing. Results: A de novo deletion of 1.55 Mb (6 cases) or 1.83 Mb (2 cases) at 7q11.23 was detected, being in 7/8 patients of paternal origin. No common breakpoint, deletion mechanism or size was found. Two cases were hemizygous for the rare T allele at rs12539160 in MLXIPL, previously associated with ASD. Inherited rare variants in ASD-related or functionally constrained genes and a de novo nonsense mutation in the UBR5 gene were identified in six cases, with higher burden in females compared with males (p=0.016). Conclusions: The increased susceptibility to ASD in patients with WBS might be due to additive effects of the common WBS deletion, inherited and de novo rare sequence variants in ASD-related genes elsewhere in the genome, with higher burden of deleterious mutations required for females, and possible hypomorphic variants in the hemizygous allele or cis-acting mechanisms on imprinting.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BMJ Publishing Group
dc.rights Copyright © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
dc.title Genetic factors contributing to autism spectrum disorder in Williams-Beuren syndrome
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1136/jmedgenet-2019-106080
dc.subject.keyword Williams-Beuren syndrome
dc.subject.keyword Autism spectrum disorders
dc.subject.keyword Comorbidity
dc.subject.keyword Exome sequencing
dc.subject.keyword Neurobehavioural phenotype
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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