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Published on: October 9, 2014
Aberrant Splicing Caused by a Novel VPS16 Variant Linked to Dystonia Type 30
Mariana Santos1, João Massano2, Alexandra Manuel Lopes3
1UnIGENe, 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. mariana.graca@ibmc.up.pt.
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.
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