Background

DYT-TOR1A is caused by a GAG deletion in the TOR1A gene. While it usually manifests as early-onset dystonia, its phenotype is extremely diverse, even within one family. Recent reports have revealed that some DYT-TOR1A cases have novel mutations in the TOR1A gene while others have mutations in both TOR1A and another DYT gene (THAP1 or SGCE). Our understanding of the correlation between genotype and phenotype is becoming increasingly complicated.

Case presentations: Here, we report on monozygotic twins who developed dystonia in childhood. The two children had different presentations in terms of onset age and dominant disturbances, but both exhibited marked diurnal fluctuation and jerking movements of the limbs as well as levodopa/levodopa-carbidopa responsiveness. These features are commonly associated with DYT/PARK-GCH1 and DYT-SGCE, yet these twins had no mutations in the GCH1 or SGCE genes. Whole exome sequencing eventually revealed a single GAG deletion in the TOR1A gene.

Conclusion

Monozygotic twins whose only mutation was a GAG deletion in TOR1A exhibited DYT/PARK-GCH1-asssociated features and jerking movements reminiscent of myoclonus. This finding may expand the spectrum of phenotypes associated with DYT-TOR1A, and suggests that levodopa has potential as a treatment for DYT-TOR1A with DYT/PARK-GCH1-associated features.

中文翻译：

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具有 DYT-TOR1A 的单卵双胞胎表现出抽搐动作和左旋多巴反应

背景

DYT- TOR1A是由TOR1A基因中的 GAG 缺失引起的。虽然它通常表现为早发性肌张力障碍，但其表型极为多样化，即​​使在一个家族中也是如此。最近的报告显示，一些 DYT- TOR1A病例在TOR1A基因中有新的突变，而另一些在TOR1A和另一个 DYT 基因（THAP1或SGCE）中都有突变。我们对基因型和表型之间相关性的理解变得越来越复杂。

病例介绍：在这里，我们报告了在儿童时期出现肌张力障碍的单卵双胞胎。这两个孩子在发病年龄和主要障碍方面有不同的表现，但都表现出明显的昼夜波动和四肢抽搐运动以及左旋多巴/左旋多巴-卡比多巴反应。这些特征通常与 DYT/PARK- GCH1和DYT- SGCE 相关，但这些双胞胎在GCH1或SGCE基因中没有突变。全外显子组测序最终揭示了TOR1A基因中的单个 GAG 缺失。

结论

唯一突变是TOR1A中 GAG 缺失的单卵双胞胎表现出与 DYT/PARK- GCH1相关的特征和让人想起肌阵挛的抽搐运动。这一发现可能会扩大与 DYT- TOR1A相关的表型谱，并表明左旋多巴具有治疗具有 DYT/PARK- GCH1相关特征的 DYT- TOR1A的潜力。