Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis
Late-onset spastic paraplegia type 10 (SPG10) family presenting with bulbar symptoms and fasciculations mimicking amyotrophic lateral sclerosis
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DOI：
10.1016/j.jns.2016.03.001
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发表时间：
2016-05-15
影响因子：
4.4
通讯作者：
Kaji, Ryuji
中科院分区：
文献类型：
--
作者：
Kaji, Seiji;Kawarai, Toshitaka;Kaji, Ryuji
编码运动蛋白HC5A的KIF5A-SPG10基因的致病突变可与常染色体显性遗传性痉挛性截瘫(ADHSP)相关。它约占ADHSP复杂形式的10%。周围神经病变、上肢远端肌萎缩和认知功能减退是最常见的附加临床特征。我们检查了一位66岁的日本妇女，表现为步态障碍和痉挛构音障碍，有6年的阳性家族史。她显示了上下运动神经元受累和束状改变的证据，因此类似于肌萎缩侧索硬化症(ALS)。遗传分析显示，在2名有症状的成员中，KIF5A(c.484C>；T，p.Arg162Trp)存在杂合变异。在4名无症状成员中也发现了这种突变，其中包括2名年龄超过78岁的老年成员。两名有症状的成员的肌电图显示运动神经元受累程度较低，远端肌肉的颤动电位较低。这份报告描述了第一个已知的具有KIF5A突变的亚洲家庭，并扩大了与KIF5A-SPG10突变相关的临床和电生理谱。考虑到我们的病例表现为假性延髓麻痹、痉挛和外露改变，KIF5A-SPG10可被认为是散发性ALS的鉴别诊断。(C)2016爱思唯尔B.V.保留所有权利。
Pathogenic mutations in the KIF5A-SPG10 gene, encoding the kinesin HC5A, can be associated with autosomal dominant hereditary spastic paraplegia (ADHSP). It accounts for about 10% of the complicated forms of ADHSP. Peripheral neuropathy, distal upper limb amyotrophy, and cognitive decline are the most common additional clinical features. We examined a 66-year-old Japanese woman manifesting gait disturbance and spastic dysarthria for 6 years with positive family history. She showed evidence of upper and lower motor neuron involvement and fasciculations, thus mimicking amyotrophic lateral sclerosis (ALS). Genetic analysis revealed a heterozygous variant in KIF5A (c.484C>T, p.Arg162Trp) in 2 symptomatic members. The mutation was also identified in 4 asymptomatic members, including 2 elderly members aged over 78 years. Electromyography in the 2 symptomatic members revealed evidence of lower motor neuron involvement and fasciculation potentials in distal muscles. This report describes the first known Asian family with a KIF5A mutation and broadens the clinical and electrophysiological spectrum associated with KIF5A-SPG10 mutations. Given that our cases showed pseudobulbar palsy, fasciculation and altered penetrance, KIF5A-SPG10 might well be considered as a differential diagnosis of sporadic ALS. (C) 2016 Elsevier B.V. All rights reserved.