OBJECTIVE We aimed to analyze prevalence, clinical, and genetic characteristics of the POLG-associated ataxias in a cohort of recessive and sporadic ataxias in adults with previously excluded acquired ataxias. METHODS We did a retrospective analysis of the medical records of 74 patients older than 18 years referred to the Research Center of Neurology between 2012 and 2019 with progressive sporadic or autosomal recessive ataxia with onset before 50 years of age. A stepwise approach in genetic testing was used. All patients with genetically confirmed POLG-associated disorders underwent clinical, biochemical, electrophysiological, and neuroimaging assessments. RESULTS In our cohort of 74 adult patients with autosomal recessive and sporadic ataxias, POLG-related disease was identified in 11 individuals (14.9 %). The median age of onset was 30 years. One patient had a positive family history. The core clinical syndrome included external ophthalmoparesis, cerebellar signs, and sensory neuropathy. In all patients, the Montreal Cognitive Assessment score was less than 26. All but 3 patients had specific brain MRI changes. Mutation spectrum of the POLG gene in our cohort is discussed. CONCLUSION Our study shows that POLG-associated ataxias comprise a significant part of the recessive and sporadic ataxias in adults in the Russian population after excluding acquired causes of ataxic disorders. We suggest first screening patients with specific clinical and (or) neuroimaging features for the population-specific common POLG mutations, followed by the NGS panel testing where necessary. In future clinical studies, thorough cognitive and neuropsychiatric profiling is needed to complete the phenotype of the POLG-related disorders.

中文翻译：

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POLG 相关性共济失调可以代表成人隐性和散发性共济失调的很大一部分

目的 我们旨在分析先前排除的获得性共济失调的成人隐性和散发性共济失调队列中 POLG 相关共济失调的患病率、临床和遗传特征。方法 我们对 2012 年至 2019 年间转诊至神经病学研究中心的 74 例 18 岁以上的 50 岁前发病的进行性散发性或常染色体隐性共济失调患者的病历进行了回顾性分析。使用了基因检测的逐步方法。所有经基因证实的 POLG 相关疾病患者都接受了临床、生化、电生理和神经影像学评估。结果 在我们的 74 名常染色体隐性和散发性共济失调成年患者队列中，在 11 名个体 (14.9 %) 中发现了 POLG 相关疾病。中位发病年龄为 30 岁。一名患者有阳性家族史。核心临床综合征包括外部眼肌麻痹、小脑体征和感觉神经病变。在所有患者中，蒙特利尔认知评估评分低于 26。除 3 名患者外，所有患者都有特定的脑部 MRI 变化。讨论了我们队列中 POLG 基因的突变谱。结论我们的研究表明，在排除共济失调的获得性原因后，POLG 相关性共济失调是俄罗斯成年人隐性和散发性共济失调的重要组成部分。我们建议首先对具有特定临床和（或）神经影像学特征的患者进行人群特异性常见 POLG 突变筛查，然后在必要时进行 NGS 面板测试。在未来的临床研究中，