新表型和深内含子变异扩展th相关多巴反应性肌张力障碍谱。

IF 4.4 2区医学 Q1 CLINICAL NEUROLOGY

Annals of Clinical and Translational Neurology Pub Date : 2025-03-27 DOI:10.1002/acn3.70013

Xiaosheng Zheng, Chenxin Ying, Nan Jin, Jinghong Ma, Xinhua Wan, Xunhua Li, Wei Luo

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引用次数: 0

摘要

大约20%的多巴反应性肌张力障碍（DRD）病例仍未得到遗传上的解决。利用全基因组测序，我们在一名年轻的DRD患者中发现了两种TH变体，包括一种新的深内含子变体。基因分析证实这种变异导致异常剪接。与典型的th相关DRD病例相比，患者表现出非典型的疾病进展，表现为全身性肌张力障碍、发作性肌张力低下、帕金森病和口腔下颌运动障碍。这些发现，包括第一个已知的深内含子TH变异，扩大了我们对TH相关DRD的表型和基因型谱的理解，有助于临床评估。

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

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.

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来源期刊

Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)

CiteScore

9.10

自引率

1.90%

发文量

218

审稿时长

8 weeks

期刊介绍： Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.