眼睑痉挛：132 例患者的基因筛查研究。
Blepharospasm: A genetic screening study in 132 patients.
机构信息
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA.
Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, 20892, USA.
出版信息
Parkinsonism Relat Disord. 2019 Jul;64:315-318. doi: 10.1016/j.parkreldis.2019.04.003. Epub 2019 Apr 2.
INTRODUCTION
Blepharospasm is a common type of focal dystonia that involves involuntary eyelid spasms and eye closure. In familial cases, an autosomal dominant pattern of inheritance is noted with reduced penetrance. Few genes have been associated with the disease including GNAL and CIZ1. A whole exome sequencing study published lately suggested TOR2A and REEP4 as potential candidate genes.
METHODS
Sanger sequencing of GNAL, CIZ1, TOR2A and REEP4 exons including exon-intron boundaries in 132 patients diagnosed primarily with blepharospasm and/or Meige's syndrome.
RESULTS
All variants detected in GNAL, CIZ1 and TOR2A seem to be benign. Sequencing of REEP4 revealed the presence of two nonsynonymous SNVs, one potential splice site variant and one indel all predicted to be damaging by in silico algorithms.
CONCLUSION
Sequencing REEP4 in larger blepharospasm cohorts and functional studies will need to be performed to further elucidate the association between REEP4 and the disease.
简介
眼睑痉挛是一种常见的局灶性肌张力障碍，涉及不自主的眼睑痉挛和闭眼。在家族性病例中，注意到常染色体显性遗传模式，外显率降低。少数基因与该疾病相关，包括 GNAL 和 CIZ1。最近发表的一项全外显子组测序研究表明 TOR2A 和 REEP4 可能是候选基因。
方法
对 132 名主要诊断为眼睑痉挛和/或 Meige 综合征的患者进行 GNAL、CIZ1、TOR2A 和 REEP4 外显子的 Sanger 测序，包括外显子-内含子边界。
结果
在 GNAL、CIZ1 和 TOR2A 中检测到的所有变体似乎都是良性的。REEP4 的测序显示存在两个非同义 SNV、一个潜在剪接位点变异和一个插入缺失，所有这些都被预测为基于计算机的算法具有破坏性。
结论
需要对更大的眼睑痉挛队列进行 REEP4 测序和功能研究，以进一步阐明 REEP4 与该疾病之间的关联。
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