Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Neurology, The East Area of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
Mol Genet Genomic Med. 2019 Jun;7(6):e663. doi: 10.1002/mgg3.663. Epub 2019 Mar 28.
The presence of more than one polyQ-related gene within a single individual is a rare incidence, which may provide the potential opportunity to study the combined effects of these spinocerebellar ataxia (SCA) genes.
We retrospectively analyzed genetic data from 112 SCA3 probands and found Patient 1 harbored expanded ATXN2 allele (33 repeats) and intermediate TBP allele (41 repeats), and Patient 2 with intermediate ATXN2 allele (32 repeats). Detailed clinical and oculomotor performances were investigated. The age at onset and oculomotor parameters of both patients were compared with matched pure SCA3 groups controlling either disease severity or CAG repeats.
Most of the clinical phenotypes and oculomotor characteristics of these two patients were common to typical SCA3 patients. Compared to pure SCA3 groups controlling disease severity, mild reduced horizontal saccade velocity could be detected in both patients. However, mild expansions of the ATXN2 allele seemed to have no influence on the age at onset of Patient 1 but might have a mild impact on Patient 2.
Our study provides supporting evidence that mild expansions of ATXN2 may have modifying effects on SCA3 phenotype. Larger control series and longitudinal data are warranted to confirm our results.
在单个个体中存在多个与 polyQ 相关的基因是一种罕见的情况，这可能为研究这些脊髓小脑共济失调（SCA）基因的联合效应提供了潜在的机会。
我们回顾性分析了 112 名 SCA3 先证者的遗传数据，发现患者 1 携带扩展的 ATXN2 等位基因（33 个重复）和中间 TBP 等位基因（41 个重复），而患者 2 则携带中间 ATXN2 等位基因（32 个重复）。详细的临床和眼动表现进行了研究。比较了两个患者的发病年龄和眼动参数与控制疾病严重程度或 CAG 重复的匹配纯 SCA3 组。
这两个患者的大多数临床表型和眼动特征与典型的 SCA3 患者相似。与控制疾病严重程度的纯 SCA3 组相比，两个患者均存在轻度水平扫视速度降低。然而，ATXN2 等位基因的轻度扩展似乎对患者 1 的发病年龄没有影响，但可能对患者 2 有轻微影响。
我们的研究提供了支持性证据，表明 ATXN2 的轻度扩展可能对 SCA3 表型具有修饰作用。需要更大的对照系列和纵向数据来证实我们的结果。
