Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy
Intranuclear inclusions in skin biopsies are not limited to neuronal intranuclear inclusion disease but can also be seen in oculopharyngodistal myopathy
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DOI：
10.1111/nan.12787
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发表时间：
2021-12-28
影响因子：
5
通讯作者：
Nishino, Ichizo
中科院分区：
文献类型：
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作者：
Ogasawara, Masashi;Eura, Nobuyuki;Nishino, Ichizo
目的眼咽远端肌病是由NOTCH2NLC(OPDM_NOTCH2NLC)、GIPC1(OPDM_GIPC1)或LRP12(OPDM_LRP12)中CGG重复序列的扩增引起的。神经元性核内包涵体病(NIID)在临床上不同于OPDM，但也是由NOTCH2NLC中CGG重复序列的扩张引起的，这可能是皮肤活检中核内包涵体的一个指标。我们调查了OPDM和具有相似病理的肌肉疾病患者的皮肤活检中核内包涵体的存在，以评估它们在皮肤活检中是否有类似的诊断结果。方法分析OPDM、NIID、OPMD、IBM和GNE肌病患者的汗腺细胞、脂肪细胞和成纤维细胞中p62阳性包涵体的频率。结果在OPDMNOTCH2NLC和1例NIID患者的3种细胞类型中均可观察到p62阳性包涵体，在6例OPDMGIPC1患者中至少有一种细胞类型可见p62阳性包涵体，在3例OPDMLRP12患者中有1例在3种细胞类型中均可观察到p62阳性包涵体。这些发现在OPMD、IBM或GNE肌病患者中没有观察到。结论皮肤活检组织中的核内包涵体不是NIID所特有的，而是存在于所有三种经基因证实的OPDM中，提示OPDM的潜在机制可能与NIID相似，而与致病基因无关。
Aims Oculopharyngodistal myopathy (OPDM) is caused by the expansion of CGG repeats in NOTCH2NLC (OPDM_NOTCH2NLC) GIPC1 (OPDM_GIPC1), or LRP12 (OPDM_LRP12). Neuronal intranuclear inclusion disease (NIID) is clinically distinct from OPDM but is also caused by the expansion of CGG repeats in NOTCH2NLC, which may be an indicator of intranuclear inclusion in skin biopsy. We investigated the presence of intranuclear inclusions in skin biopsies from patients with OPDM and muscle diseases with a similar pathology to evaluate whether they will have similar diagnostic findings on skin biopsy. Methods We analysed the frequency of p62-positive intranuclear inclusions in sweat gland cells, adipocytes and fibroblasts in skin biopsy samples from patients with OPDM (OPDM_NOTCH2NLC [n = 2], OPDM_GIPC1 [n = 6] and OPDM_LRP12 [n = 3]), NIID (n = 1), OPMD (n = 1), IBM (n = 4) and GNE myopathy (n = 2). Results The p62-postive intranuclear inclusions were observed in all three cell types in both patients with OPDM_NOTCH2NLC and a patient with NIID, in at least one cell type in all six patients with OPDM_GIPC1, and all in three cell types in one of the three patients with OPDM_LRP12. These findings were not observed in patients with OPMD, IBM or GNE myopathy. Conclusion Intranuclear inclusions in skin biopsy samples are not specific to NIID and are found in all three types of genetically confirmed OPDM, suggesting that the underlying mechanism of OPDM may be similar to NIID, regardless of causative genes.