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A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents

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dc.contributor.author Gangfuß, Andrea
dc.contributor.author Lochmüller, Hanns
dc.contributor.author Töpf, Ana
dc.contributor.author O'Hehir, Emily
dc.contributor.author Horvath, Rita
dc.contributor.author Kölbel, Heike
dc.contributor.author Schweiger, Bernd
dc.contributor.author Schara-Schmidt, Ulrike
dc.contributor.author Roos, Andreas
dc.date.accessioned 2021-12-21T11:07:09Z
dc.date.available 2021-12-21T11:07:09Z
dc.date.issued 2022
dc.identifier.citation Gangfuß A, Lochmüller H, Töpf A, O'Heir E, Horvath R, Kölbel H et al. A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents. Am J Med Genet A. 2022 Jan;188(1):283-291. DOI: 10.1002/ajmg.a.62494
dc.identifier.issn 1552-4833
dc.identifier.uri http://hdl.handle.net/10230/51905
dc.description.abstract CSDE1 encodes the cytoplasmic cold shock domain-containing protein E1 (CSDE1), which is highly conserved across species and functions as an RNA-binding protein involved in translationally coupled mRNA turnover. CSDE1 displays a bidirectional role: promoting and repressing the translation of RNAs but also increasing and decreasing the abundance of RNAs. Preclinical studies highlighted an involvement of CSDE1 in different forms of cancer. Moreover, CSDE1 is highly expressed in human embryonic stem cells and plays a role in neuronal migration and differentiation. A genome-wide association study suggested CSDE1 as a potential autism-spectrum disorder risk gene. A multicenter next generation sequencing approach unraveled likely causative heterozygous variants in CSDE1 in 18 patients, identifying a new autism spectrum disorder-related syndrome consisting of autism, intellectual disability, and neurodevelopmental delay. Since then, no further patients with CSDE1 variants have been reported in the literature. Here, we report a 9.5-year-old girl from a consanguineous family of Turkish origin suffering from profound delayed speech and motor development, moderate intellectual disability, neurologic and psychiatric symptoms as well as hypoplasia of corpus callosum and mildly reduced brain volume on brain magnetic resonance imaging associated with a recurrent de novo mutation in CSDE1 (c.367C > T; p.R123*) expanding the phenotypical spectrum associated with pathogenic CSDE1 variants.
dc.description.sponsorship Funding: Andreas Roos received funding from The French Muscular Dystrophy Association (AFM-Téléthon) (grant 21644). Andreas Roos, Andrea Gangfuß, and Ulrike Schara-Schmidt also acknowledge funding in the framework of the NME-GPS project by the European Regional Development Fund (ERDF). Rita Horvath was supported by the European Research Council (309548), the Wellcome Investigator Award (109915/Z/15/Z), the Medical Research Council (UK) (MR/N025431/1), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z) and the Newton Fund (UK/Turkey, MR/N027302/1). Hanns Lochmüller receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research, and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). AT is supported by the Horizon 2020 research and innovation program via grant 779257 “Solve-RD.” Sequencing and analysis were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141. Andreas Roos received funding from The French Muscular Dystrophy Association (AFM-Téléthon) (grant 21644). Andreas Roos, Andrea Gangfuß, and Ulrike Schara-Schmidt also acknowledge funding in the framework of the NME-GPS project by the European Regional Development Fund (ERDF). Rita Horvath was supported by the European Research Council (309548), the Wellcome Investigator Award (109915/Z/15/Z), the Medical Research Council (UK) (MR/N025431/1), the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z), the Newton Fund (UK/Turkey, MR/N027302/1) and the Lily Foundation and the Evelyn Trust. Hanns Lochmüller receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research, and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C), the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279). AT is supported by the Horizon 2020 research and innovation program via grant 779257 “Solve-RD.” Sequencing and analysis were provided by the Broad Institute of MIT and Harvard Center for Mendelian Genomics (Broad CMG) and was funded by the National Human Genome Research Institute, the National Eye Institute, and the National Heart, Lung and Blood Institute grant UM1 HG008900 and in part by National Human Genome Research Institute grant R01 HG009141
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Wiley
dc.rights © 2021 Andrea Gangfuß et al. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.subject.other Genètica
dc.subject.other RNA
dc.subject.other Deficiència mental
dc.subject.other Músculs -- Malalties
dc.title A de novo CSDE1 variant causing neurodevelopmental delay, intellectual disability, neurologic and psychiatric symptoms in a child of consanguineous parents
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1002/ajmg.a.62494
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/779257
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309548
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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