Novel Phenotypes and Deep Intronic Variant Expand TH‐Associated Dopa‐Responsive Dystonia Spectrum

ABSTRACT Approximately 20% of dopa‐responsive dystonia (DRD) cases remain genetically unresolved. Using whole‐genome sequencing, we identified two TH variants in a young DRD patient, including a novel deep intronic variant. Minigene assays confirmed that this variant causes aberrant splicing. The pa...

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Bibliographic Details
Main Authors: Xiaosheng Zheng, Chenxin Ying, Nan Jin, Jinghong Ma, Xinhua Wan, Xunhua Li, Wei Luo
Format: Article
Language:English
Published: Wiley 2025-05-01
Series:Annals of Clinical and Translational Neurology
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Online Access:https://doi.org/10.1002/acn3.70013
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Summary:ABSTRACT Approximately 20% of dopa‐responsive dystonia (DRD) cases remain genetically unresolved. Using whole‐genome sequencing, we identified two TH variants in a young DRD patient, including a novel deep intronic variant. Minigene assays confirmed that this variant causes aberrant splicing. The patient exhibited an atypical disease progression compared with typical TH‐associated DRD cases, presenting with generalized dystonia, episodic hypotonia, Parkinsonism, and oromandibular dyskinesias. These findings, including the first known documented deep intronic TH variant, expand our understanding of TH‐associated DRD's phenotypic and genotypic spectrum, aiding clinical evaluation.
ISSN:2328-9503