STUB1 Mutations as Possible Genetic Modifiers in Spinocerebellar Ataxia Type 8

IF 7.4 1区医学 Q1 CLINICAL NEUROLOGY Movement Disorders Pub Date : 2024-07-04 DOI:10.1002/mds.29910

Raquel Baviera-Muñoz MD, Lidón Carretero-Vilarroig MSc, Ana Pedro-Ibor MSc, Teresa Jaijo PhD, Andrea Del Valle-Carranza PhD, Irene Martínez-Torres MD, Jose M. Millán PhD, Luis Bataller MD, Elena Aller PhD

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Abstract

Background

Spinocerebellar ataxia type 8 (SCA8) is a dominantly inherited expansion disorder with highly variable penetrance. ATXN8OS/ATXN8 expanded alleles have been identified in association with other types of hereditary ataxias, pointing to a possible genetic synergism.

Objectives

We aimed to further investigate the molecular background of patients with SCA8 diagnosis.

Methods

Patients were selected from our cohort of 346 families. A total of 14 probands with SCA8 underwent additional investigation through exome sequencing.

Results

Pathogenic heterozygous STUB1 variants were found in 21.4% of SCA8 patients (3 of 14) compared to only 0.5% in the non-SCA8 group (1 of 222), indicating a statistically significant association (P < 0.05).

Conclusions

The findings reported in this study might suggest a genetic synergism between STUB1 and ATXN8OS/ATXN8 expanded alleles. Further studies are needed to validate this observation and better define the clinical impact of this genetic interaction.

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STUB1 基因突变可能是脊髓小脑共济失调 8 型的遗传修饰因子。

背景：脊髓小脑共济失调 8 型（SCA8）是一种显性遗传扩展性疾病，具有高度可变的渗透性。已发现ATXN8OS/ATXN8扩增等位基因与其他类型的遗传性共济失调相关，这表明可能存在遗传协同作用：我们旨在进一步研究确诊为 SCA8 患者的分子背景：方法：从我们的 346 个家庭中选取患者。共有 14 名 SCA8 患者接受了外显子组测序：结果：在 21.4% 的 SCA8 患者（14 人中有 3 人）中发现了致病性杂合子 STUB1 变异，而在非 SCA8 组中仅有 0.5% 的患者（222 人中有 1 人）发现了致病性杂合子 STUB1 变异，这表明两者之间存在统计学意义上的显著关联（P 结论：SCA8 患者的 STUB1 变异与非 SCA8 患者的 STUB1 变异之间存在显著关联：本研究报告的结果可能表明，STUB1 和 ATXN8OS/ATXN8 扩增等位基因之间存在遗传协同作用。需要进一步的研究来验证这一观察结果，并更好地确定这种遗传相互作用的临床影响。© 2024 作者简介运动障碍》由 Wiley Periodicals LLC 代表国际帕金森和运动障碍协会出版。

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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.

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