BACKGROUND Variations in TOR1A were thought to be associated with early-onset isolated dystonia. The variant S287Y (NM_000113.2: c.860C > A, p. Ser287Tyr, rs766483672) was found in our late-onset isolated dystonia patient. This missense variant is adjacent to R288Q (c.863G > A, p. Arg288Gln), which was reported to be associated with isolated dystonia. The potentially pathogenic role of S287Y is not conclusively known. METHODS Cytological and molecular biological analyses were performed in vitro to determine whether this variant damages the structure and function of the cell. RESULTS Compared with the SH-SY5Y cells overexpressing wild-type TOR1A, the cells overexpressing the protein with S287Y have an enlarged peri-nuclear space. The same changes in nuclear morphology were also found in the cells overexpressing the pathogenic variants ΔE (NM_000113.2:c.904_906delGAG, p. Glu302del), F205I (NM_000113.2:c.613 T > A, p. Phe205Ile), and R288Q (NM_000113.2:c.863G > A, p. Arg288Gln). Mutated proteins with S287Y presented a higher tendency to form dimers under reducing conditions. The same tendencies were observed in other mutated proteins but not in wild-type torsinA. CONCLUSIONS TorsinA with S287Y damages the structure of the cell nucleus and may be a novel pathogenic mutation that causes isolated dystonia.

中文翻译：

---

新突变p的细胞分析。TOR1A中的Ser287Tyr在迟发性孤立性肌张力障碍中。

背景技术TOR1A的变异被认为与早期发作的孤立性肌张力障碍有关。在我们的迟发性分离性肌张力障碍患者中发现了变体S287Y（NM_000113.2：c.860C> A，p。Ser287Tyr，rs766483672）。该错义变体与R288Q（c.863G> A，第Arg288Gln页）相邻，据报道与孤立的肌张力障碍有关。S287Y的潜在致病作用尚无定论。方法在体外进行细胞学和分子生物学分析，以确定该变体是否破坏细胞的结构和功能。结果与过表达野生型TOR1A的SH-SY5Y细胞相比，过表达带有S287Y蛋白的细胞具有更大的核周空间。在过表达致病变体ΔE（NM_000113.2：c.904_906delGAG，p.Glu302del），F205I（NM_000113.2：c.613 T> A，p.Phe205Ile）的细胞中也发现了相同的核形态变化。 R288Q（NM_000113.2：c.863G> A，p.Arg288Gln）。具有S287Y的突变蛋白在还原条件下具有更高的形成二聚体的趋势。在其他突变蛋白中也观察到了相同的趋势，但在野生型TorsA中却没有。结论带有S287Y的TorsinA会破坏细胞核的结构，可能是导致孤立性肌张力障碍的新型致病突变。在其他突变蛋白中也观察到了相同的趋势，但在野生型TorsA中却没有。结论带有S287Y的TorsinA会破坏细胞核的结构，可能是导致孤立性肌张力障碍的新型致病突变。在其他突变蛋白中也观察到了相同的趋势，但在野生型TorsA中却没有。结论带有S287Y的TorsinA会破坏细胞核的结构，可能是导致孤立性肌张力障碍的新型致病突变。