Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Department of Physical Therapy, Kagoshima University of School of Health Sciences, Kagoshima, Japan.
J Neurol Neurosurg Psychiatry. 2023 Aug;94(8):622-630. doi: 10.1136/jnnp-2022-330769. Epub 2023 Mar 22.
GGC repeat expansions have been associated with various neurogenerative disorders, including neuronal intranuclear inclusion disease and inherited peripheral neuropathies (IPNs). However, only a few -related disease studies in IPN have been reported, and the clinical and genetic spectra remain unclear. Thus, this study aimed to describe the clinical and genetic manifestations of -related IPNs.
Among 2692 Japanese patients clinically diagnosed with IPN/Charcot-Marie-Tooth disease (CMT), we analysed repeat expansion in 1783 unrelated patients without a genetic diagnosis. Screening and repeat size determination of repeat expansion were performed using repeat-primed PCR and fluorescence amplicon length analysis-PCR.
repeat expansions were identified in 26 cases of IPN/CMT from 22 unrelated families. The mean median motor nerve conduction velocity was 41 m/s (range, 30.8-59.4), and 18 cases (69%) were classified as intermediate CMT. The mean age of onset was 32.7 (range, 7-61) years. In addition to motor sensory neuropathy symptoms, dysautonomia and involuntary movements were common (44% and 29%). Furthermore, the correlation between the age of onset or clinical symptoms and the repeat size remains unclear.
These findings of this study help us understand the clinical heterogeneity of -related disease, such as non-length-dependent motor dominant phenotype and prominent autonomic involvement. This study also emphasise the importance of genetic screening, regardless of the age of onset and type of CMT, particularly in patients of Asian origin, presenting with intermediate conduction velocities and dysautonomia.
GGC 重复扩展与各种神经退行性疾病有关，包括神经元核内包涵体病和遗传性周围神经病 (IPN)。然而，仅有少数与 IPN 相关的疾病研究被报道，且临床和遗传谱仍不清楚。因此，本研究旨在描述与 -相关的 IPN 的临床和遗传表现。
在 2692 名临床诊断为 IPN/Charcot-Marie-Tooth 病 (CMT) 的日本患者中，我们分析了 1783 名无遗传诊断的无关患者中的 重复扩展。使用重复引物 PCR 和荧光扩增子长度分析-PCR 进行 重复扩展的筛查和重复大小确定。
在 22 个不相关的家族中，从 26 例 IPN/CMT 中鉴定出了 重复扩展。运动神经传导速度的平均中位值为 41 m/s（范围，30.8-59.4），18 例（69%）被归类为中间型 CMT。发病年龄的平均值为 32.7 岁（范围，7-61 岁）。除了运动感觉神经病症状外，自主神经功能障碍和不自主运动也很常见（44%和 29%）。此外，发病年龄或临床症状与重复大小之间的相关性尚不清楚。
本研究的这些发现有助于我们了解与 -相关疾病的临床异质性，例如非长度依赖性运动为主的表型和明显的自主神经受累。本研究还强调了遗传筛查的重要性，无论发病年龄和 CMT 类型如何，特别是在具有中间传导速度和自主神经功能障碍的亚洲起源的患者中。
