目的：本文介绍了由于KIF5Ap.Arg1007Lys引起的肌萎缩侧索硬化症（ALS）的第一份报告，改变剪接的变体。方法：一例病例为54岁男性，出现进行性步态困难和不平衡，随后出现轻度帕金森病，痉挛,神经病,共济失调,和以皮层下额叶受累为主的认知障碍。脑MRI显示双侧顶叶明显萎缩。肌电图显示慢性弥漫性神经源性改变。由于他父亲的类似症状的阳性病史和其他10名家庭成员的ALS诊断，进行了广泛的基因检测。结果：GRN基因筛查，C9orf72,TARDBP,SOD1,FUS,MAPT突变,遗传性共济失调小组，平淡无奇。全外显子组测序显示c.3020G>A（p。Arg1007Lys）KIF5A基因中的突变，后来在两名受影响的亲属中得到证实。讨论：与之前关于KIF5A相关ALS的报告类似，我们的索引案例，病程温和，生存期延长。然而,由于即使在同一家庭成员中，进展速度和生存时间也有所不同，其他因素可能在起作用。此外,我们的索引案例和他的父亲显示了重叠的ALS特征，痉挛性截瘫,Charcot-Marie-Tooth病2型和额颞叶痴呆.因此,我们建议在鉴别诊断中考虑KIF5A突变，特别是在痉挛的重叠特征存在的情况下，神经病,小脑共济失调,和痴呆症。
This paper presents the first report of amyotrophic lateral sclerosis (ALS) kindred due to the KIF5A p.Arg1007Lys, a splice-altering variant.
An index
case was a 54-year-old male who developed progressive gait difficulty and imbalance followed by mild parkinsonism, spasticity, neuropathy, ataxia, and cognitive impairment with predominant subcortical frontal involvement. Brain MRI showed marked bilateral parietal lobes atrophy. Electromyography demonstrated chronic diffuse neurogenic changes. Due to the positive history of similar symptoms in his father and the diagnosis of ALS in 10 other family members, extensive genetic testing was pursued.
Genetic screening for GRN, C9orf72, TARDBP, SOD1, FUS, MAPT mutations, and hereditary ataxia panel, was unremarkable. Whole-exome sequencing revealed c.3020G > A (p.Arg1007Lys) mutation in the KIF5A gene, later confirmed in two affected relatives.
Similar to previous
reports on KIF5A-related ALS, our index
case, had a mild disease course with prolonged survival. However, as the rate of progression and survival time differed even among the same family members, other factors were probably at play. Additionally, our index
case and his father displayed features overlapping ALS, spastic paraplegia, Charcot-Marie-Tooth disease type 2, and frontotemporal dementia. Therefore, we suggest considering KIF5A mutations in the differential diagnosis, particularly in the presence of overlapping features of spasticity, neuropathy, cerebellar ataxia, and dementia.
