Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
Mov Disord. 2022 Aug;37(8):1756-1761. doi: 10.1002/mds.29079. Epub 2022 May 31.
Recently, p.R383H in TFG was identified as the disease cause in a family with α-synucleinopathy and amyotrophic lateral sclerosis (ALS). However, no further replication has been conducted in larger cohorts.
The aim was to explore the genetic role of TFG in α-synucleinopathy and ALS.
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.
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.
Rare variants of TFG were not enriched in α-synucleinopathy and ALS. However, we could not deny the potential pathogenicity of specific variants such as p.R383H. Further exploration is still necessary. © 2022 International Parkinson and Movement Disorder Society.
最近，TFG 中的 p.R383H 被确定为一个具有α-突触核蛋白病和肌萎缩侧索硬化症（ALS）的家族的疾病原因。然而，在更大的队列中尚未进行进一步的复制。
本研究旨在探讨 TFG 在 α-突触核蛋白病和 ALS 中的遗传作用。
我们对帕金森病（PD）、ALS、多系统萎缩（MSA）、痉挛性截瘫（N=2709）患者和 7536 名对照者的全外显子组测序进行了罕见蛋白编码变异分析。
在 PD 和 MSA 中发现了 9 个罕见变异，在 MSA 中发现了 2 个。一名 PD 患者携带相同的变异 p.R383H。同样，这名患者以左侧运动迟缓伴僵硬为首发症状，表现为早发性 PD。然而，在基因水平上，TFG 的罕见变异并未在患者中富集。
TFG 的罕见变异在 α-突触核蛋白病和 ALS 中没有富集。然而，我们不能否认特定变异（如 p.R383H）的潜在致病性。仍需进一步探索。 © 2022 国际帕金森病和运动障碍学会。
