Missense variant contribution to USP9X-female syndrome

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• dc.contributor.author Jolly, Lachlan A.
• dc.contributor.author Pérez Jurado, Luis Alberto
• dc.contributor.author Gecz, Jozef
• dc.date.accessioned 2021-01-14T07:12:56Z
• dc.date.available 2021-01-14T07:12:56Z
• dc.date.issued 2020
• dc.description.abstract USP9X is an X-chromosome gene that escapes X-inactivation. Loss or compromised function of USP9X leads to neurodevelopmental disorders in males and females. While males are impacted primarily by hemizygous partial loss-of-function missense variants, in females de novo heterozygous complete loss-of-function mutations predominate, and give rise to the clinically recognisable USP9X-female syndrome. Here we provide evidence of the contribution of USP9X missense and small in-frame deletion variants in USP9X-female syndrome also. We scrutinise the pathogenicity of eleven such variants, ten of which were novel. Combined application of variant prediction algorithms, protein structure modelling, and assessment under clinically relevant guidelines universally support their pathogenicity. The core phenotype of this cohort overlapped with previous descriptions of USP9X-female syndrome, but exposed heightened variability. Aggregate phenotypic information of 35 currently known females with predicted pathogenic variation in USP9X reaffirms the clinically recognisable USP9X-female syndrome, and highlights major differences when compared to USP9X-male associated neurodevelopmental disorders.
• dc.format.mimetype application/pdf
• dc.identifier.citation Jolly LA, Parnell E, Gardner AE, Corbett MA, Pérez-Jurado LA, Shaw M et al. Missense variant contribution to USP9X-female syndrome. NPJ Genom Med. 2020; 5(1):53. DOI: 10.1038/s41525-020-00162-9
• dc.identifier.doi http://dx.doi.org/10.1038/s41525-020-00162-9
• dc.identifier.issn 2056-7944
• dc.identifier.uri http://hdl.handle.net/10230/46165
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof NPJ Genom Med. 2020; 5(1):53
• dc.rights © The Author(s) 2020. 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.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Development
• dc.subject.keyword Genetics research
• dc.subject.keyword Neurodevelopmental disorders
• dc.title Missense variant contribution to USP9X-female syndrome
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion