Evaluation of the Core Formation Process in Congenital Neuromuscular Disease With Uniform Type 1 Fiber and Central Core Disease
Evaluation of the Core Formation Process in Congenital Neuromuscular Disease With Uniform Type 1 Fiber and Central Core Disease
复制标题
均匀 1 型纤维先天性神经肌肉疾病和中央核心疾病的核心形成过程评估
DOI：
10.1093/jnen/nlaa104
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发表时间：
2020
影响因子：
3.2
通讯作者：
Nishino Ichizo
中科院分区：
文献类型：
--
作者：
Ogasawara Masashi;Ogawa Megumu;Nonaka Ikuya;Hayashi Shinichiro;Noguchi Satoru;Nishino Ichizo
典型的中心性核心病(CCD)的病理特征是核心型的存在，并伴随着1型纤维的一致性。1型纤维均一型先天性神经肌肉病(CNMDU1)的病理特征是1型纤维均一，但无肌纤维结构异常改变。有趣的是，典型的CCD和40%的CNMDU1病例是由相同的RYR1突变引起的，因此CNMDU1被认为是CCD的早期先兆。为了更好地了解CNMDU1的本质，我们使用RYR1、Triadin和TOM20的免疫组织化学方法重新评估了16例CNMDU1患者的肌肉活检组织，并将其与36例典型的CCD患者的肌肉活检组织进行了比较。在CCD中，核心区存在RYR1和Triadin，而核心区不存在TOM20。有趣的是，在5例具有RYR1突变的CNMDU1病例中，RYR1和Triadin类似地存在于核心区，而TOM20在肌膜下区域缺失。此外，核心位置与疾病持续时间或进展之间存在相关性--处于更晚期的老年患者拥有更集中的核心。我们的结果表明，由RYR1突变引起的CNMDU1是一种事实上的核心肌病。
Typical central core disease (CCD) is characterized pathologically by the presence of a core and is accompanied by type 1 fiber uniformity. Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is characterized pathologically by the presence of type 1 fiber uniformity but without the abnormal structural changes in muscle fibers. Interestingly, typical CCD and 40% of CNMDU1 cases are caused by the same mutations inRYR1, and thus CNMDU1 has been considered an early precursor to CCD. To better understand the nature of CNMDU1, we re-evaluated muscle biopsies from 16 patients with CNMDU1 using immunohistochemistry to RYR1, triadin and TOM20, and compared this to muscle biopsies from 36 typical CCD patients. In CCD, RYR1, and triadin were present in the core regions, while TOM20 was absent in the core regions. Interestingly, in 5 CNMDU1 cases with theRYR1mutation, RYR1, and triadin were similarly present in core-like areas, while TOM20 was absent in the subsarcolemmal region. Furthermore, there was a correlation between the core position and the disease duration or progression—the older patients in more advanced stages had more centralized cores. Our results indicate that CNMDU1 due toRYR1mutation is a de facto core myopathy.