Nuzhnyi Evgenii, Seliverstov Yury, Klyushnikov Sergey, Krylova Tatiana, Tsygankova Polina, Bychkov Igor, Zakharova Ekaterina, Konovalov Rodion, Fedin Pavel, Abramycheva Natalia, Illarioshkin Sergey
Research Center of Neurology, Volokolamskoe shosse 80, Moscow, 125367, Russia.
Research Center of Neurology, Volokolamskoe shosse 80, Moscow, 125367, Russia.
Clin Neurol Neurosurg. 2021 Feb;201:106462. doi: 10.1016/j.clineuro.2020.106462. Epub 2021 Jan 7.
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.
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.
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.
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.
我们旨在分析一组先前已排除获得性共济失调的成人隐性和散发性共济失调患者中，与聚合酶γ（POLG）相关的共济失调的患病率、临床特征和遗传特征。
我们对2012年至2019年间转诊至神经学研究中心的74例18岁以上患者的病历进行了回顾性分析，这些患者患有50岁之前起病的进行性散发性或常染色体隐性共济失调。采用逐步进行基因检测的方法。所有基因确诊为与POLG相关疾病的患者均接受了临床、生化、电生理和神经影像学评估。
在我们这组74例患有常染色体隐性和散发性共济失调的成年患者中，11例（14.9%）被确诊为与POLG相关的疾病。发病年龄中位数为30岁。1例患者有家族史阳性。核心临床综合征包括眼外肌麻痹、小脑体征和感觉神经病变。所有患者的蒙特利尔认知评估得分均低于26分。除3例患者外，其余患者均有特定的脑部MRI改变。我们讨论了该队列中POLG基因的突变谱。
我们的研究表明，在排除共济失调性疾病的获得性病因后，与POLG相关的共济失调在俄罗斯人群的成人隐性和散发性共济失调中占很大一部分。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针对人群特异性常见POLG突变的筛查，必要时进行二代测序（NGS） panel检测。在未来的临床研究中，需要进行全面的认知和神经精神分析以完善与POLG相关疾病的表型。
