Progressive myoclonic ataxia as an initial symptom of typical type I sialidosis with NEU1 mutation.

IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2024-11-01 Epub Date: 2024-10-31 DOI:10.1002/acn3.52212
Jingjing Lin, Yun-Lu Li, Bo-Li Chen, Hui-Zhen Su, Yi-Heng Zeng, Rui-Huang Zeng, Yu-Duo Zhang, Ru-Kai Chen, Nai-Qing Cai, Yi-Kun Chen, Ru-Ying Yuan, Jun-Yi Jiang, Xiang-Ping Yao, Ning Wang, Wan-Jin Chen, Kang Yang
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Abstract

Objective: Expand genetic screening for atypical Type I sialidosis (ST-1) could address its underdiagnosed in both progressive myoclonic ataxia (PMA) and ataxia patients. To evaluate the potential founder effect of mutation in the population.

Methods: We enrolled 231 patients with PMA or ataxia from the First Affiliated Hospital of Fujian Medical University. Through Whole Exome Sequencing and Sanger sequencing, we identified the causative gene in patients. Haplotype analysis was employed to explore a potential founder effect of the NEU1 c.544A>G mutation.

Results: A total of 31 patients from 23 unrelated families were genetically diagnosed with ST-1. A significant 80.6% of these patients were homozygous for the c.544A>G mutation. We discovered six different NEU1 variants, including two novel mutations: c.951_968del and c.517T>G. The mean age of onset was 18.0 ± 7.1 years. The clinical spectrum of ST-1 featured ataxia and myoclonus as the most common initial symptoms. Over 40% suffered from controlled generalized tonic-clonic seizures. Mobility and independence varied greatly across the cohort. Cherry-red spots were rare, occurring in just 9.5% (2/21) of patients. Brain MRIs were typically unremarkable, except for two patients with unusual findings. EEGs showed diffuse paroxysmal activity in 17 patients. The c.544A>G mutation in NEU1 is a founder variant in Fujian, with a unique haplotype prevalent in East Asians.

Interpretation: ST-1 should be suspected in patients with PMA or ataxia in Southeast China, even without macular cherry-red spots and seizures, and the premier test could be a variant screening of the founder variant NEU1 c.544A>G.

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进行性肌阵挛性共济失调是典型的 I 型神经鞘磷脂病(NEU1 基因突变)的最初症状。
目的:扩大非典型Ⅰ型硅铝酸盐症(ST-1)的基因筛查可解决进行性肌阵挛性共济失调(PMA)和共济失调患者诊断不足的问题。评估突变在人群中的潜在奠基效应:方法:我们从福建医科大学附属第一医院招募了231名进行性肌阵挛性共济失调(PMA)或共济失调患者。通过全外显子组测序和 Sanger 测序,我们确定了患者的致病基因。采用单倍型分析探讨了NEU1 c.544A>G突变的潜在奠基效应:结果:共有来自 23 个无血缘关系家庭的 31 名患者被基因诊断为 ST-1。其中80.6%的患者为c.544A>G突变的同源基因。我们发现了六种不同的 NEU1 变异,包括两种新型突变:c.951_968del 和 c.517T>G。ST-1的临床表现以共济失调和肌阵挛为最常见的首发症状。40%以上的患者会出现控制性全身强直-阵挛发作。患者的活动能力和独立性差异很大。樱桃红色斑很少见,仅占患者总数的9.5%(2/21)。除两名患者有异常发现外,脑部核磁共振成像通常无异常。17 名患者的脑电图显示有弥漫性阵发性活动。NEU1的c.544A>G突变是福建的创始变异,其独特的单倍型在东亚人中很普遍:在中国东南地区,即使没有黄斑樱桃红色斑点和癫痫发作,PMA 或共济失调患者也应怀疑 ST-1,而首要的检测方法可能是对 NEU1 c.544A>G 的创始变异进行变异筛查。
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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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