TOR2A Variants in Blepharospasm.
TOR2A Variants in Blepharospasm.
复制标题
眼睑痉挛的 TOR2A 变体。
DOI：
10.5334/tohm.825
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
LeDoux MS
中科院分区：
文献类型：
--
作者：
Saeirad S;LeDoux MS
遗传因素与眼睑痉挛(BSP)的发病机制有关，BSP是一种以过度眨眼和非自愿眼皮闭合为特征的肌张力障碍。先前的研究在一个多世代家系内的三名BSP患者和三名携带者中发现了一种共分离的有害TOR2A变异体(GRCH38/HG38，NC_000009.12：G.127733410G>；A，NM_001085347.3：C.568C>；T，p.Arg190Cys)。据报道，其他TOR2A变异在肌张力障碍患者中也存在。Sanger测序用于筛选307名患有单纯性BSP或BSP合并肌张力障碍的受试者，这些受试者影响额外的解剖节段(BSP+)。我们还利用计算工具统一评估了以前报道的TOR2A变种的危害性和潜在的致病性。在我们的307名受试者中，在TOR2A的编码或连续剪接部位区域没有高度有害的TOR2A变异。在BSP/BSP+表型的患者中，TOR2A基因高度有害的变异是罕见的。对300多名BSP患者进行了TOR2A，一种TOR1A(DYT1)同源基因的变异筛查。在我们的队列中没有发现高度有害的变异。TOR2A在BSP和其他形式的肌张力障碍中的作用仍不确定。
Genetic factors have been implicated in the pathogenesis of blepharospasm (BSP), a dystonia characterized by excessive blinking and involuntary eyelid closure. Previous research identified a co-segregating deleterious TOR2A variant (GRCh38/hg38, NC_000009.12: g.127733410G>A, NM_001085347.3:c.568C>T, p. Arg190Cys) in three subjects with BSP and three carriers within a multi-generation pedigree. Other TOR2A variants have been reported in patients with dystonia. Sanger sequencing was used to screen a cohort of 307 subjects with isolated BSP or BSP-plus dystonia affecting additional anatomical segments (BSP+). We also utilized computational tools to uniformly assess the deleteriousness and potential pathogenicity of previously reported TOR2A variants. There were no highly deleterious TOR2A variants in the coding or contiguous splice site regions of TOR2A within our cohort of 307 subjects. Highly deleterious variants in TOR2A are rare in patients with BSP/BSP+ phenotypes. Over 300 patients with BSP were screened for variants in TOR2A, a TOR1A (DYT1) homologue. No highly deleterious variants were identified in our cohort. The role of TOR2A in BSP and other forms of dystonia remains indeterminant.
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影响因子：
4.1
作者：
LeDoux MS
通讯作者：
LeDoux MS
影响因子：
3.5
作者：
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通讯作者：
Breakefield, XO
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30.8
作者：
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通讯作者：
Shendure, Jay
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2
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通讯作者：
LeDoux, Mark S.
影响因子：
11
作者：
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通讯作者：
Berardelli, A