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Prominent Movement Disorders in RNU2-2-Related Spliceosomopathy.

Magdalena Krygier·Ugo Sorrentino·Matias Wagner·Marta Zawadzka·Anna Lemska·Maria Mazurkiewicz-Bełdzińska·Michael Zech
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Abstract

Pediatric movement disorders often overlap with neurodevelopmental diseases, suggesting shared molecular mechanisms. Variants in small nuclear RNA (snRNA) genes encoding spliceosome components have recently been associated with neurodevelopmental disorders, termed "RNUopathies." We analyzed genome sequencing data from 14 patients with undiagnosed pediatric movement disorders for pathogenic variants in snRNA genes. We identified recurrent de novo RNU2-2 variants (n.35A > G and n.4G > A) in two patients with intellectual disability, epilepsy, and hyperkinetic movement disorders. RNA sequencing of fibroblasts in one patient showed no characteristic transcriptomic signature. Spliceosomopathies should be considered in neurodevelopmental disorders and developmental and epileptic encephalopathies with hyperkinetic features.

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HumansRNA, Small NuclearFemaleMovement DisordersChildMaleChild, PreschoolIntellectual DisabilityEpilepsyNeurodevelopmental DisordersRNU2‐2RNUopathiesdevelopmental and epileptic encephalopathymovement disordersneurodevelopmental disordersJournal Article

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Magdalena Krygier, Ugo Sorrentino, Matias Wagner, Marta Zawadzka, Anna Lemska, Maria Mazurkiewicz-Bełdzińska, Michael Zech. 2026-05-27. Prominent Movement Disorders in RNU2-2-Related Spliceosomopathy.. https://doi.org/10.1002/acn3.70442

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