University of Thessaly, University Hospital of Larissa, Neurology Department, Larissa, GR.
Department of Molecular Neuroscience Institute of Neurology, University College London, London, UK.
Tremor Other Hyperkinet Mov (N Y). 2020 Jun 12;10:5. doi: 10.5334/tohm.61.
Several European studies examined the role of C9orf72 repeat expansion in patients with Huntington-disease like phenotypes (HD-L). The scope of our study is to investigate the expansion frequency in a Greek HD-L cohort and the meta-analysis of all published cases. This will be of use in genetic counseling of these cases.
A cohort of 74 patients with HD-L and 67 healthy controls were screened for the C9orf72 expansion status. Case-controls comparison was assessed with the Pearson's chi-square statistic for a 2 × 2 table.A systematic database search was conducted and seven studies, including the current study, were considered eligible for inclusion in a meta-analysis considering a total of 812 patients with HD phenocopies. Pooled mutation frequency was calculated using a Random Effects model or the Mantel-Haezsel fixed effects model, depending on the observed heterogeneity.
In our cohort, one patient was found to have a pathologic expansion of C9orf72, and none from the control group (chi-square: 0.91, p-value: 0.34). Pooled mutation frequency was found at 2% (CI: 1-3%) with low heterogeneity (I:15%).
Based on this meta-analysis the recommendation for genetic testing for C9orf72 expansions is further solidified.
几项欧洲研究探讨了 C9orf72 重复扩展在亨廷顿病样表型（HD-L）患者中的作用。我们研究的范围是调查希腊 HD-L 队列中的扩展频率以及所有已发表病例的荟萃分析。这将有助于对这些病例进行遗传咨询。
对 74 名具有 HD-L 和 67 名健康对照的患者进行了 C9orf72 扩展状态的筛查。使用 2×2 表的 Pearson 卡方检验评估病例对照比较。进行了系统的数据库搜索，考虑到总共 812 名 HD 表型患者，有 7 项研究（包括本研究）被认为符合纳入荟萃分析的条件。使用随机效应模型或曼特尔-海瑟尔固定效应模型计算合并突变频率，具体取决于观察到的异质性。
在我们的队列中，发现 1 名患者存在 C9orf72 病理性扩展，而对照组中没有（卡方：0.91，p 值：0.34）。合并突变频率为 2%（CI：1-3%），异质性低（I：15%）。
基于这项荟萃分析，进一步证实了对 C9orf72 扩展进行基因检测的建议。
