Hobara Takahiro, Ando Masahiro, Higuchi Yujiro, Yuan Jun-Hui, Yoshimura Akiko, Kojima Fumikazu, Noguchi Yutaka, Takei Jun, Hiramatsu Yu, Nozuma Satoshi, Nakamura Tomonori, Adachi Tadashi, Toyooka Keiko, Yamashita Toru, Sakiyama Yusuke, Hashiguchi Akihiro, Matsuura Eiji, Okamoto Yuji, Takashima Hiroshi
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
J Neurol Neurosurg Psychiatry. 2025 Jan 16;96(2):140-149. doi: 10.1136/jnnp-2024-333403.
The causative genes for over 60% of inherited peripheral neuropathy (IPN) remain unidentified. This study endeavours to enhance the genetic diagnostic rate in IPN cases by conducting screenings focused on non-coding repeat expansions.
We gathered data from 2424 unrelated Japanese patients diagnosed with IPN, among whom 1555 cases with unidentified genetic causes, as determined through comprehensive prescreening analyses, were selected for the study. Screening for CGG non-coding repeat expansions in , and genes was conducted using PCR and long-read sequencing technologies.
We identified CGG repeat expansions in from 44 cases, establishing it as the fourth most common aetiology in Japanese IPN. Most cases (29/37) exhibited distal limb weakness, without ptosis, ophthalmoplegia, facial muscle weakness or bulbar palsy. Neurogenic changes were frequently observed in both needle electromyography (97%) and skeletal muscle tissue (100%). In nerve conduction studies, 28 cases primarily showed impairment in motor nerves without concurrent involvement of sensory nerves, consistent with the phenotype of hereditary motor neuropathy. In seven cases, both motor and sensory nerves were affected, resembling the Charcot-Marie-Tooth (CMT) phenotype. Importantly, the mean CGG repeat number detected in the present patients was significantly shorter than that of patients with -oculopharyngodistal myopathy (p<0.0001). Additionally, and repeat expansions were absent in our IPN cases.
We initially elucidate repeat expansions as a prevalent cause of CMT, highlighting the necessity for an adapted screening strategy in clinical practice, particularly when addressing patients with IPN.
超过60%的遗传性周围神经病（IPN）的致病基因仍未明确。本研究旨在通过针对非编码重复序列扩增进行筛查，提高IPN病例的基因诊断率。
我们收集了2424例诊断为IPN的无关日本患者的数据，其中1555例经全面预筛查分析确定为基因病因不明的病例被选入本研究。使用聚合酶链反应（PCR）和长读长测序技术对 、 和 基因中的CGG非编码重复序列扩增进行筛查。
我们在44例患者中鉴定出 基因的CGG重复序列扩增，使其成为日本IPN中第四常见的病因。大多数病例（29/37）表现为远端肢体无力，无眼睑下垂、眼肌麻痹、面部肌肉无力或延髓麻痹。针极肌电图（97%）和骨骼肌组织（100%）中均频繁观察到神经源性改变。在神经传导研究中，28例主要表现为运动神经损伤，感觉神经未同时受累，符合遗传性运动神经病的表型。7例患者的运动和感觉神经均受累，类似夏科 - 马里 - 图斯（CMT）表型。重要的是，本研究中检测到的患者平均CGG重复次数明显短于伴有 - 眼咽远端肌病的患者（p<0.0001）。此外，我们的IPN病例中未发现 和 基因的重复序列扩增。
我们首次阐明 基因重复序列扩增是CMT的常见病因，强调了在临床实践中采用适应性筛查策略的必要性，特别是在处理IPN患者时。
需注意，原文中部分基因名称未给出完整信息，我按原样保留了 、 和 。你可根据实际情况补充完整。
