Welcome to the UPF Digital Repository

Yield of clinically reportable genetic variants in unselected cerebral palsy by whole genome sequencing

Show simple item record

dc.contributor.author van Eyk, Clare L.
dc.contributor.author Webber, Dani L.
dc.contributor.author Minoche, André E.
dc.contributor.author Pérez Jurado, Luis Alberto
dc.contributor.author Corbett, Mark A.
dc.contributor.author Gardner, Alison E.
dc.contributor.author Berry, Jesia G.
dc.contributor.author Harper, Kelly
dc.contributor.author MacLennan, Alastair H.
dc.contributor.author Gecz, Jozef
dc.date.accessioned 2021-10-20T06:29:20Z
dc.date.available 2021-10-20T06:29:20Z
dc.date.issued 2021
dc.identifier.citation van Eyk CL, Webber DL, Minoche AE, Pérez-Jurado LA, Corbett MA, Gardner AE, Berry JG, Harper K, MacLennan AH, Gecz J. Yield of clinically reportable genetic variants in unselected cerebral palsy by whole genome sequencing. NPJ Genom Med. 2021;6(1):74. DOI: 10.1038/s41525-021-00238-0
dc.identifier.issn 2056-7944
dc.identifier.uri http://hdl.handle.net/10230/48712
dc.description.abstract Cerebral palsy (CP) is the most common cause of childhood physical disability, with incidence between 1/500 and 1/700 births in the developed world. Despite increasing evidence for a major contribution of genetics to CP aetiology, genetic testing is currently not performed systematically. We assessed the diagnostic rate of genome sequencing (GS) in a clinically unselected cohort of 150 singleton CP patients, with CP confirmed at >4 years of age. Clinical grade GS was performed on the proband and variants were filtered, and classified according to American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines. Variants classified as pathogenic or likely pathogenic (P/LP) were further assessed for their contribution to CP. In total, 24.7% of individuals carried a P/LP variant(s) causing or increasing risk of CP, with 4.7% resolved by copy number variant analysis and 20% carrying single nucleotide or indel variants. A further 34.7% carried one or more rare, high impact variants of uncertain significance (VUS) in variation intolerant genes. Variants were identified in a heterogeneous group of genes, including genes associated with hereditary spastic paraplegia, clotting and thrombophilic disorders, small vessel disease, and other neurodevelopmental disorders. Approximately 1/2 of individuals were classified as likely to benefit from changed clinical management as a result of genetic findings. In addition, no significant association between genetic findings and clinical factors was detectable in this cohort, suggesting that systematic sequencing of CP will be required to avoid missed diagnoses.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof NPJ Genom Med. 2021;6(1):74
dc.rights © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Yield of clinically reportable genetic variants in unselected cerebral palsy by whole genome sequencing
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41525-021-00238-0
dc.subject.keyword Genetic testing
dc.subject.keyword Medical genomics
dc.subject.keyword Molecular medicine
dc.subject.keyword Neonatal brain damage
dc.subject.keyword Neurodevelopmental disorders
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account


In collaboration with Compliant to Partaking