Abstract
Dystonia is a hyperkinetic movement disorder characterized by sustained or intermittent involuntary muscle contractions, causing abnormal postures and/or repetitive movements. In this report, we identified a novel heterozygous splice-site variant in VPS16 (NM_022575.4:c.240+3G>C) in a patient with cervical and upper limb dystonia without other neurological or extra-neurological features. Analysis of patient’s blood mRNA showed disruption of exon 3/intron 3 donor splice-site, leading to exon 3 skipping, which predictably results in a frameshift [p.(Ala48Valfs*14)]. Despite the scarcity of splice-affecting variants described in VPS16-related dystonia, our report contributes with the first fully characterized variant at the mRNA level.
Data availability
Research data have not been archived at a public repository but are available from the corresponding author upon reasonable request.
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Acknowledgements
We sincerely thank the patient for the participation in this study.
Funding
M. S. acknowledges funding from FCT-Fundação para a Ciência e a Tecnologia, I.P. through the program DL 57/2016 - Norma Transitória.
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M.S. performed gene expression experiments and prepared the figure and table. J.M. identified the patient and performed clinical data collection. Initial genetic and bioinformatics analysis was performed by A.M.L. and A.F.B., and results were validated by J.O. The work was supervised by J.P.F and J.O. The manuscript was initially drafted by M.S. and J.M. All authors critically revised the manuscript and approved the final version.
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The study was conducted in accordance with the Declaration of Helsinki. Written and verbal informed consent was obtained from the patient. The authors confirm that the approval of the institutional review board is not required for this work.
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Santos, M., Massano, J., Lopes, A.M. et al. Aberrant Splicing Caused by a Novel VPS16 Variant Linked to Dystonia Type 30. Neurogenetics 24, 215–218 (2023). https://doi.org/10.1007/s10048-023-00720-0
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DOI: https://doi.org/10.1007/s10048-023-00720-0