由CST3致病性变异引起的成人发病白质脑病的两个日本家庭

IF 3.2 3区医学 Q1 CLINICAL NEUROLOGY

Journal of the Neurological Sciences Pub Date : 2025-09-26 DOI:10.1016/j.jns.2025.123708

Kenta Orimo , Takashi Matsukawa , Kazutaka Shiomi , Ryoji Goto , Akihiko Mitsutake , Yumiko Kuromi , Nozomu Matsuda , Kazuaki Kanai , Ryo Kurokawa , Hiroyuki Ishiura , Jun Mitsui , Junko Nomoto , Masaki Tanaka , Yosuke Omae , Yosuke Kawai , Katsushi Tokunaga , Shoji Tsuji , Tatsushi Toda

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引用次数: 0

摘要

CST3 （NM_000099.4）编码胱抑素C，该基因的C端截断变异最近被报道可引起成人发病的脑白质病，其特征是头痛、短暂的神经系统症状和明显的影像学表现。我们报告了来自两个日本家族的四名患者，其中一人携带一种新的变异（c.358-2_395del）。来自一个家庭的三名患者在20岁左右出现慢性头痛，而来自另一个家庭的患者直到50多岁才出现症状。对c.358-2_395del患者的mRNA分析显示，剪接改变导致帧内缺失（p.Lys120_Gln133del），这是第一个不导致截断蛋白的CST3变异。这些发现拓宽了我们对cst3相关白质脑病临床和遗传谱的认识。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Two Japanese families with adult-onset leukoencephalopathy caused by pathogenic variants in CST3

CST3 (NM_000099.4) encodes cystatin C, whose C-terminal truncating variants in this gene have recently been reported to cause adult-onset leukoencephalopathy, characterized by headaches, transient neurological symptoms, and distinct imaging findings. We present four patients from two Japanese families, including one with a novel variant (c.358-2_395del). Three patients from one family developed chronic headaches around the age of 20, whereas the patient from the other family remained asymptomatic until his fifties. mRNA analysis of the patient with c.358-2_395del revealed a splicing alteration leading to an in-frame deletion (p.Lys120_Gln133del), representing the first CST3 variant that does not result in a truncated protein. These findings broaden our understanding of the clinical and genetic spectra of CST3-related leukoencephalopathy (114 words).

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来源期刊

Journal of the Neurological Sciences 医学-临床神经学

CiteScore

7.60

自引率

2.30%

发文量

313

审稿时长

22 days

期刊介绍： The Journal of the Neurological Sciences provides a medium for the prompt publication of original articles in neurology and neuroscience from around the world. JNS places special emphasis on articles that: 1) provide guidance to clinicians around the world (Best Practices, Global Neurology); 2) report cutting-edge science related to neurology (Basic and Translational Sciences); 3) educate readers about relevant and practical clinical outcomes in neurology (Outcomes Research); and 4) summarize or editorialize the current state of the literature (Reviews, Commentaries, and Editorials). JNS accepts most types of manuscripts for consideration including original research papers, short communications, reviews, book reviews, letters to the Editor, opinions and editorials. Topics considered will be from neurology-related fields that are of interest to practicing physicians around the world. Examples include neuromuscular diseases, demyelination, atrophies, dementia, neoplasms, infections, epilepsies, disturbances of consciousness, stroke and cerebral circulation, growth and development, plasticity and intermediary metabolism.