Hanaoka Yoshiyuki, Akiyama Tomoyuki, Yoshinaga Harumi, Miyamoto Ryousuke, Kawarai Toshitaka, Kaji Ryuji, Kobayashi Katsuhiro
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan.
Department of Child Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital, Okayama, Japan.
Brain Dev. 2021 Aug;43(7):783-788. doi: 10.1016/j.braindev.2021.03.005. Epub 2021 Apr 5.
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.
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.
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.
DYT-TOR1A 由 TOR1A 基因中的 GAG 缺失引起。虽然它通常表现为早发性肌张力障碍，但其表型极为多样，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，而其他病例在 TOR1A 和另一个 DYT 基因（THAP1 或 SGCE）中都有突变。我们对基因型与表型之间相关性的理解正变得越来越复杂。
在此，我们报告一对在童年时期出现肌张力障碍的同卵双胞胎。这两个孩子在发病年龄和主要障碍方面表现不同，但都表现出明显的昼夜波动、肢体抽搐运动以及左旋多巴/左旋多巴 - 卡比多巴反应性。这些特征通常与 DYT/PARK - GCH1 和 DYT - SGCE 相关，但这对双胞胎在 GCH1 或 SGCE 基因中没有突变。全外显子测序最终揭示 TOR1A 基因中有一个单一的 GAG 缺失。
仅在 TOR1A 基因中有 GAG 缺失的同卵双胞胎表现出与 DYT/PARK - GCH1 相关的特征以及类似肌阵挛的抽搐运动。这一发现可能会扩大与 DYT - TOR1A 相关的表型谱，并表明左旋多巴有可能用于治疗具有 DYT/PARK - GCH1 相关特征的 DYT - TOR1A。
