GGC repeat expansions in NOTCH2NLC causing a phenotype of distal motor neuropathy and myopathy.
GGC repeat expansions in NOTCH2NLC causing a phenotype of distal motor neuropathy and myopathy.
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NOTCH2NLC 中的 GGC 重复扩增导致远端运动神经病和肌病的表型
DOI：
10.1002/acn3.51371
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发表时间：
2021-06
影响因子：
5.3
通讯作者：
Wang Z
中科院分区：
文献类型：
--
作者：
Yu J;Luan XH;Yu M;Zhang W;Lv H;Cao L;Meng L;Zhu M;Zhou B;Wu XR;Li P;Gang Q;Liu J;Shi X;Liang W;Jia Z;Yao S;Yuan Y;Deng J;Hong D;Wang Z
在N0TCH 2NLC的5'非翻译区中GGC重复的扩增已经与中枢神经系统的各种神经发生性病症以及最近的眼咽远端肌病相关。本研究旨在报告在电生理和病理学上具有神经性和肌病特征的远端无力患者，这些患者在NOTCH 2NLC中存在GGC重复扩增。实施全外显子组测序（WES）和长读段测序以鉴定候选基因。此外，我们还回顾了现有的临床资料以及与周围神经和肌肉活检相关的病理变化。我们在三名不相关的患者中鉴定并验证了NOTCH 2NLC的GGC重复扩增，这些患者在初始WES阴性结果后表现出主要影响下肢远端肌肉的进行性无力。我们在肌纤维和雪旺细胞的细胞核中发现了含有多种蛋白沉积物的核内包涵体。这些患者的临床特征与远端运动神经病和镶边空泡性肌病的诊断相一致。这些表型丰富了与NOTCH2NLC相关的重复扩增障碍（NRED）相关的特征类别，并提供了进一步的证据，证明NRED的神经系统症状不仅包括脑，脊髓和周围神经损伤，还包括肌病，并且可能存在重叠症状。
The expansion of GGC repeat in the 5' untranslated region of the NOTCH2NLC has been associated with various neurogenerative disorders of the central nervous system and, more recently, oculopharyngodistal myopathy. This study aimed to report patients with distal weakness with both neuropathic and myopathic features on electrophysiology and pathology who present GGC repeat expansions in the NOTCH2NLC. Whole‐exome sequencing (WES) and long‐read sequencing were implemented to identify the candidate genes. In addition, the available clinical data and the pathological changes associated with peripheral nerve and muscle biopsies were reviewed and studied. We identified and validated GGC repeat expansions of NOTCH2NLC in three unrelated patients who presented with progressive weakness predominantly affecting distal lower limb muscles, following negative results in an initial WES. We found intranuclear inclusions with multiple proteins deposits in the nuclei of both myofibers and Schwann cells. The clinical features of these patients are compatible with the diagnosis of distal motor neuropathy and rimmed vacuolar myopathy. These phenotypes enrich the class of features associated with NOTCH2NLC‐related repeat expansion disorders (NRED), and provide further evidence that the neurological symptoms of NRED include not only brain, spinal cord, and peripheral nerves damage, but also myopathy, and that overlapping symptoms might exist.
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影响因子：
48
作者：
Sedlazeck FJ;Rescheneder P;Smolka M;Fang H;Nattestad M;von Haeseler A;Schatz MC
通讯作者：
Schatz MC
重新定义神经元核内包涵体病的临床病理学谱。
影响因子：
5.3
作者：
Chen H;Lu L;Wang B;Cui G;Wang X;Wang Y;Raza HK;Min Y;Li K;Cui Y;Miao Z;Wan B;Sun M;Xu X
通讯作者：
Xu X
影响因子：
9.9
作者：
Sone, J.;Tanaka, F.;Sobue, G.
通讯作者：
Sobue, G.
影响因子：
1.1
作者：
Wang, Yan;Wang, Bo;Hong, Daojun
通讯作者：
Hong, Daojun
人类特异性 NOTCH2NLC 基因中 GGC 重复序列的扩展与特发性震颤相关。
影响因子：
14.5
作者：
Sun, Qi-Ying;Xu, Qian;Tang, Bei-Sha
通讯作者：
Tang, Bei-Sha