Santos Mariana, Massano João, Lopes Alexandra Manuel, Brandão Ana Filipa, Freixo João Parente, Oliveira Jorge
UnIGENe, IBMC-Institute for Molecular and Cell Biology, i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135, Porto, Portugal.
Department of Neurology, Centro Hospitalar Universitário de São João, and Faculty of Medicine University of Porto, Porto, Portugal.
Neurogenetics. 2023 Jul;24(3):215-218. doi: 10.1007/s10048-023-00720-0. Epub 2023 May 24.
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.
肌张力障碍是一种运动亢进性运动障碍，其特征为持续或间歇性的不自主肌肉收缩，导致异常姿势和/或重复性动作。在本报告中，我们在一名患有颈部和上肢肌张力障碍且无其他神经或神经外特征的患者中，鉴定出VPS16基因（NM_022575.4:c.240+3G>C）的一种新的杂合剪接位点变异。对患者血液mRNA的分析显示外显子3/内含子3供体剪接位点破坏，导致外显子3跳跃，这可预测地导致移码突变[p.(Ala48Valfs*14)]。尽管在VPS16相关肌张力障碍中描述的影响剪接的变异很少见，但我们的报告首次在mRNA水平上对一个变异进行了全面表征。
