PDF(Pubmed)
Abstract：
We investigate the etiology of amyotrophic lateral sclerosis (ALS) in a 35-year-old woman presenting with progressive weakness in her left upper limb. Prior to sequencing, a comprehensive neurological work-up was performed, including neurological examination, electrophysiology, biomarker assessment, and brain and spinal cord MRI. Six months before evaluation, the patient experienced weakness and atrophy in her left hand, accompanied by brisk reflexes and Hoffman sign in the same arm. Electroneuromyography revealed lower motor neuron involvement in three body regions. Neurofilament light chains were elevated in her cerebrospinal fluid. Brain imaging showed asymmetrical T2 hyperintensity of the corticospinal tracts and T2 linear hypointensity of the precentral gyri. Trio genome sequencing identified a likely pathogenic de novo variant in the KIF1A gene (NM_001244008.2): c.574A>G, p.(Ile192Val). Pathogenic variants in KIF1A have been associated with a wide range of neurological manifestations called KIF1A-associated neurological diseases (KAND). This report describes a likely pathogenic de novo variant in KIF1A associated with ALS, expanding the phenotypic spectrum of KAND and our understanding of the pathophysiology of ALS.
摘要：
我们调查了一名35岁女性的肌萎缩侧索硬化症（ALS）的病因，该女性的左上肢进行性无力。在测序之前，进行了全面的神经系统检查，包括神经检查,电生理学,生物标志物评估，脑和脊髓MRI.评估前六个月，患者的左手出现了虚弱和萎缩，伴随着敏捷的反应和霍夫曼的信号在同一只手臂上。神经肌电图显示较低的运动神经元参与了三个身体区域。她的脑脊液中神经丝轻链升高。脑成像显示皮质脊髓束的不对称T2高强度和中央回的T2线性低张力。三体基因组测序确定了KIF1A基因中可能的致病性从头变异（NM_001244008.2）：c.574A>G，p.(Ile192Val)。KIF1A的致病变体与称为KIF1A相关神经系统疾病（KAND）的广泛神经系统表现有关。本报告描述了与ALS相关的KIF1A中可能的致病性从头变异，扩大KAND的表型谱和我们对ALS病理生理学的理解。
