Expanded ATXN3 CAG Repeat is Stable in Human Purkinje Cells

IF 7.7 1区医学 Q1 CLINICAL NEUROLOGY

Movement Disorders Pub Date : 2026-08-08 DOI:10.1002/mds.70465

Hasnahana Chetia, Laura Kus, Erika Sipos, Nathaniel Heintz, Kert Mätlik

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引用次数: 0

Abstract

Background Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by an abnormally long polyglutamine‐encoding CAG repeat in the ATXN3 gene. Objectives We aimed to determine whether somatic expansion of the mutant ATXN3 ( mATXN3 ) CAG repeat is present in the output cell of the cerebellar cortex, the Purkinje cell (PC), in individuals affected with SCA3. Methods We combined sorting of cell nuclei from post‐mortem brain tissue, transcriptome analysis‐based confirmation of sample purity, and high‐depth sequencing of ATXN3 exon 10 amplicons to analyze the stability of mATXN3 CAG repeat in PCs in individuals with SCA3. Results We demonstrated that the expansion of mATXN3 CAG repeat in PCs is minimal, comparable with cerebellar granule neurons, and the repeat is more stable in PCs compared with striatal medium spiny neurons. Conclusion The modest somatic expansion of the mATXN3 CAG repeat observed in PCs is likely not responsible for their loss in individuals with SCA3. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

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扩增ATXN3 CAG重复序列在人类浦肯野细胞中是稳定的

脊髓小脑性共济失调3型（SCA3）是一种神经退行性疾病，由ATXN3基因中异常长的聚谷氨酰胺编码CAG重复引起。我们旨在确定突变ATXN3 (mATXN3) CAG重复序列的体细胞扩增是否存在于SCA3患者的小脑皮层输出细胞浦肯野细胞（PC）中。方法采用死后脑组织细胞核分选、基于转录组分析的样品纯度确认和ATXN3外显子10扩增子的高深度测序，分析SCA3患者pc中mATXN3 CAG重复序列的稳定性。结果我们发现mATXN3 CAG重复序列在PCs中的扩增很小，与小脑颗粒神经元相当，并且与纹状体中棘神经元相比，该重复序列在PCs中的扩增更稳定。结论：在pc中观察到的适度的mATXN3 CAG重复扩增可能不是SCA3患者丢失的原因。©2026作者。Wiley期刊有限责任公司代表国际帕金森和运动障碍学会出版的《运动障碍》。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Movement Disorders 医学-临床神经学

CiteScore

13.30

自引率

8.10%

发文量

371

审稿时长

12 months

期刊介绍： Movement Disorders publishes a variety of content types including Reviews, Viewpoints, Full Length Articles, Historical Reports, Brief Reports, and Letters. The journal considers original manuscripts on topics related to the diagnosis, therapeutics, pharmacology, biochemistry, physiology, etiology, genetics, and epidemiology of movement disorders. Appropriate topics include Parkinsonism, Chorea, Tremors, Dystonia, Myoclonus, Tics, Tardive Dyskinesia, Spasticity, and Ataxia.