Mutation Screening of TFG in α-Synucleinopathy and Amyotrophic Lateral Sclerosis
Mutation Screening of TFG in α-Synucleinopathy and Amyotrophic Lateral Sclerosis
复制标题
α-突触核蛋白病和肌萎缩侧索硬化症中 TFG 的突变筛查
DOI：
10.1002/mds.29079
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发表时间：
2022-05-31
影响因子：
8.6
通讯作者：
Shang, Huifang
中科院分区：
文献类型：
--
作者：
Li, Chunyu;Lin, Junyu;Shang, Huifang
背景最近，在一个α-突触核病和肌萎缩侧索硬化症(ALS)家系中，TFG中的p.R383H被确定为致病原因。然而，没有在更大的队列中进行进一步的复制。目的探讨转铁蛋白G基因在α-突触核病和ALS中的遗传作用。方法对帕金森病(PD)、肌萎缩侧索硬化症(ALS)、多系统萎缩(MSA)、痉挛性截瘫(N=2709)患者和7536例正常对照的罕见蛋白编码变异进行全外显子测序分析。结果在PD和MSA中分别发现9个和2个罕见变异。1例帕金森病患者携带相同的pR383H型突变。同样，该患者发展为早发性帕金森病，以左侧运动迟缓和僵硬为首发症状。然而，在基因水平上，罕见的TFG变异在患者中并未得到丰富。结论TFG罕见变异体在α-突触核病和ALS中不富含。然而，我们不能否认特定变异体的潜在致病性，例如p.R383H。进一步的探索仍然是必要的。(C)2022年国际帕金森病和运动障碍协会。
Background Recently, p.R383H in TFG was identified as the disease cause in a family with alpha-synucleinopathy and amyotrophic lateral sclerosis (ALS). However, no further replication has been conducted in larger cohorts. Objective The aim was to explore the genetic role of TFG in alpha-synucleinopathy and ALS. Methods We analyzed the rare protein-coding variants in patients with Parkinson's disease (PD), ALS, multiple system atrophy (MSA), spastic paraplegia (N = 2709), and 7536 controls with whole-exome sequencing. Results Nine rare variants were identified in PD and two in MSA. One PD patient carried the same variant p.R383H. Similarly, this patient developed early-onset PD with bradykinesia and rigidity on the left side as the initial symptoms. However, at the gene level, rare variants of TFG were not enriched in patients. Conclusions Rare variants of TFG were not enriched in alpha-synucleinopathy and ALS. However, we could not deny the potential pathogenicity of specific variants such as p.R383H. Further exploration is still necessary. (c) 2022 International Parkinson and Movement Disorder Society.