CGG Repeat Expansion in NOTCH2NLC Causing Overlapping Oculopharyngodistal Myopathy and Neuronal Intranuclear Inclusion Disease With Diffusion Weighted Imaging Abnormality in the Cerebellum.

IF 2.9 3区 医学 Q2 CLINICAL NEUROLOGY Journal of Clinical Neurology Pub Date : 2024-11-01 DOI:10.3988/jcn.2023.0486
Jing Ma, Huiqiu Zhang, Bing Meng, Jiangbo Qin, Hongye Liu, Xiaomin Pang, Rongjuan Zhao, Juan Wang, Xueli Chang, Junhong Guo, Wei Zhang
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Abstract

Background and purpose: CGG repeat expansion in the 5' untranslated region (5'UTR) of the Notch 2 N-terminal-like C gene (NOTCH2NLC) has been associated with neuronal intranuclear inclusion disease (NIID) and oculopharyngodistal myopathy type 3 (OPDM3). Few OPDM3 patients have been reported. This report describes two OPDM3 patients with novel imaging findings who presented the typical features of NIID, and reviews all OPDM3 cases available in the literature.

Methods: The available clinical, imaging, and pathological information was reviewed and investigated. CGG repeat expansion in the 5'UTR of NOTCH2NLC was tested using the repeat-primed polymerase chain reaction (PCR), followed by the fluorescence amplicon-length PCR to determine the number of CGG repeats.

Results: Our two OPDM3 patients and most patients reported in the literature developed the typical clinical characteristics of NIID, including leukoencephalopathy, peripheral neuropathy, cognitive deterioration, pigmentary retinopathy, ataxia, tremor, acute encephalitis-like episodes, pigmentary retinopathy, miosis, and sensorineural hearing loss. In addition to typical imaging findings of NIID, our two patients exhibited diffusion weighted imaging (DWI) hyperintensities in the middle cerebellar peduncles, which have not been described previously. Muscle biopsies revealed rimmed vacuoles and p62-positive intranuclear inclusions in the myofibers in both patients. The skin biopsy performed in one patient detected typical eosinophilic intranuclear inclusions. Genetic analysis identified CGG repeat expansion in NOTCH2NLC as the causative mutation in the two patients.

Conclusions: Our two patients with OPDM3 had clinical characteristics of NIID and exhibited DWI abnormality in the cerebellum. Our results indicate that OPDM3 is within the spectrum of NIID and that DWI hyperintensities in the cerebellum are helpful for diagnosing NIID or OPDM3.

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NOTCH2NLC的CGG重复扩增导致重叠性眼耳鼻喉肌病和小脑弥散加权成像异常的神经元核内包涵体病
背景和目的:Notch 2 N-terminal-like C基因(NOTCH2NLC)5'非翻译区(5'UTR)的CGG重复扩增与神经元核内包涵体病(NIID)和眼耳鼻喉肌病3型(OPDM3)有关。有关 OPDM3 患者的报道很少。本报告描述了两名有新影像学发现的 OPDM3 患者,他们具有 NIID 的典型特征,并回顾了文献中的所有 OPDM3 病例:方法:对现有的临床、影像学和病理学资料进行了回顾和研究。采用重复引物聚合酶链反应(PCR)检测了NOTCH2NLC 5'UTR中的CGG重复扩增,然后用荧光扩增子长度PCR确定CGG重复的数量:我们的两名 OPDM3 患者和文献中报道的大多数患者都具有 NIID 的典型临床特征,包括白质脑病、周围神经病变、认知功能退化、色素性视网膜病变、共济失调、震颤、急性脑炎样发作、色素性视网膜病变、瞳孔缩小和感音神经性听力损失。除了典型的 NIID 影像学检查结果外,我们的两名患者还表现出小脑中干的弥散加权成像(DWI)高密度,这在以前从未有过描述。肌肉活检显示,两名患者的肌纤维中均存在边缘空泡和 p62 阳性核内包涵体。一名患者的皮肤活检发现了典型的嗜酸性核内包涵体。遗传学分析发现,NOTCH2NLC的CGG重复扩增是这两名患者的致病突变:我们的两名 OPDM3 患者具有 NIID 的临床特征,并表现出小脑 DWI 异常。我们的研究结果表明,OPDM3属于NIID的范畴,小脑的DWI高密度有助于诊断NIID或OPDM3。
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来源期刊
Journal of Clinical Neurology
Journal of Clinical Neurology 医学-临床神经学
CiteScore
4.50
自引率
6.50%
发文量
0
审稿时长
>12 weeks
期刊介绍: The JCN aims to publish the cutting-edge research from around the world. The JCN covers clinical and translational research for physicians and researchers in the field of neurology. Encompassing the entire neurological diseases, our main focus is on the common disorders including stroke, epilepsy, Parkinson''s disease, dementia, multiple sclerosis, headache, and peripheral neuropathy. Any authors affiliated with an accredited biomedical institution may submit manuscripts of original articles, review articles, and letters to the editor. The JCN will allow clinical neurologists to enrich their knowledge of patient management, education, and clinical or experimental research, and hence their professionalism.
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