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Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion

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dc.contributor.author McMacken, Grace M.
dc.contributor.author Lochmüller, Hanns
dc.contributor.author Bansagi, Boglarka
dc.contributor.author Pyle, Angela
dc.contributor.author Lochmüller, Angela
dc.contributor.author Chinnery, Patrick F.
dc.contributor.author Laurie, Steven, 1973-
dc.contributor.author Beltran, Sergi
dc.contributor.author Matalonga, Leslie
dc.contributor.author Horvath, Rita
dc.date.accessioned 2020-10-26T10:17:44Z
dc.date.available 2020-10-26T10:17:44Z
dc.date.issued 2020
dc.identifier.citation McMacken G, Lochmüller H, Bansagi B, Pyle A, Lochmüller A, Chinnery PF, Laurie S, Beltran S, Matalonga L, Horvath R. Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion. J Neurol. 2020 Jul 12;263:3643-9. DOI: 10.1007/s00415-020-10059-3
dc.identifier.issn 0340-5354
dc.identifier.uri http://hdl.handle.net/10230/45574
dc.description.abstract Background: Behr syndrome is a clinically distinct, but genetically heterogeneous disorder characterized by optic atrophy, progressive spastic paraparesis, and motor neuropathy often associated with ataxia. The molecular diagnosis is based on gene panel testing or whole-exome/genome sequencing. Methods: Here, we report the clinical presentation of two siblings with a novel genetic form of Behr syndrome. We performed whole-exome sequencing in the two patients and their mother. Results: Both patients had a childhood-onset, slowly progressive disease resembling Behr syndrome, starting with visual impairment, followed by progressive spasticity, weakness, and atrophy of the lower legs and ataxia. They also developed scoliosis, leading to respiratory problems. In their late 30's, both siblings developed a hypertrophic cardiomyopathy and died of sudden cardiac death at age 43 and 40, respectively. Whole-exome sequencing identified the novel homozygous c.627_629del; p.(Gly210del) deletion in UCHL1. Conclusions: The presentation of our patients raises the possibility that hypertrophic cardiomyopathy may be an additional feature of the clinical syndrome associated with UCHL1 mutations, and highlights the importance of cardiac follow-up and treatment in neurodegenerative disease associated with UCHL1 mutations.
dc.description.sponsorship The study was supported by the Newton Fund UK/Turkey (MR/N027302/1 to HL and RH), the Medical Research Council (UK) (MR/N025431/1 to RH), the Wellcome Investigator fund (109915/Z/15/Z to RH), the Lily Foundation UK (to RH), the European Research Council (309548 to RH), and the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z to HL and RH). HL 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). The study was further supported by the Horizon 2020 research and innovation program via grant 779257 “Solve-RD”. Data were analyzed using the RD-Connect Genome-Phenome Analysis platform developed under FP7/2007-2013 funded project (grant agreement no. 305444).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Springer
dc.relation.ispartof J Neurol. 2020 Jul 12;263:3643-9
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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Behr syndrome and hypertrophic cardiomyopathy in a family with a novel UCHL1 deletion
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1007/s00415-020-10059-3
dc.subject.keyword Ataxia
dc.subject.keyword Behr syndrome
dc.subject.keyword Hereditary spastic paraplegia
dc.subject.keyword Neurogenetics
dc.subject.keyword Whole exome sequencing
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/309548
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/779257
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/305444
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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