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- Title
Genetic analysis of IRF2BPL in a Taiwanese dystonia cohort: The genotype and phenotype correlation.
- Authors
Chen, Pin‐Shiuan; Chen, Ying‐Fa; Chiu, Jian‐Ying; Wu, Meng‐Chen; Tai, Chun‐Hwei; Chang, Yung‐Yee; Lan, Min‐Yu; Lee, Ni‐Chung; Lin, Chin‐Hsien
- Abstract
Objective: IRF2BPL mutation has been associated with a rare neurodevelopmental disorder with abnormal movements, including dystonia. However, the role of IRF2BPL in dystonia remains elusive. We aimed to investigate IRF2BPL mutations in a Taiwanese dystonia cohort. Methods: A total of 300 unrelated patients with molecularly unassigned isolated (n = 256) or combined dystonia (n = 44) were enrolled between January 2015 and July 2023. The IRF2BPL variants were analyzed based on whole exome sequencing. The in silico prediction of the identified potential pathogenic variant was performed to predict its pathogenicity. We also compared the clinical and genetic features to previous literature reports. Results: We identified one adolescent patient carrying a de novo heterozygous pathogenic variant of IRF2BPL, c.379C>T (p.Gln127Ter), who presented with generalized dystonia, developmental regression, and epilepsy (0.33% of our dystonia cohort). This variant resides within the polyglutamine (poly Q) domain before the first PEST sequence block of the IRF2BPL protein, remarkably truncating the protein structure. Combined with other patients with IRF2BPL mutations in the literature (n = 60), patients with variants in the poly Q domain have a higher rate of nonsense mutations (p < 0.001) and epilepsy (p = 0.008) than patients with variants in other domains. Furthermore, as our index patient, carriers with substitutions before the first PEST sequence block have significantly older age of onset (p < 0.01) and higher non‐epilepsy symptoms, including generalized dystonia (p = 0.003), and ataxia (p = 0.003). Interpretation: IRF2BPL mutation is a rare cause of dystonia in our population. Mutations in different domains of IRF2BPL exhibit different phenotypes.
- Subjects
MOVEMENT disorders; DYSTONIA; PHENOTYPES; NONSENSE mutation; GENETIC variation; PROTEIN structure; GENETIC correlations
- Publication
Annals of Clinical & Translational Neurology, 2024, Vol 11, Issue 6, p1557
- ISSN
2328-9503
- Publication type
Article
- DOI
10.1002/acn3.52072