福建医科大学Kang Yang等研究人员合作发现，LOC642361/NUTM2B-AS1的CGG重复扩增通常表现为眼咽远端型肌病。该项研究成果于2023年12月29日在线发表在《遗传学报》上。

研究人员利用重复引物PCR和长序列测序技术，从3个无血缘关系的家族中鉴定出了12名LOC642361/NUTM2B-AS1基因CGG重复扩增的患者，他们通常表现为眼咽远端型肌病。CGG重复扩增的范围为161-669个重复单位。大多数患者表现为上睑下垂、眼球运动受限、吞咽困难、构音障碍和弥漫性四肢肌无力。只有一名患者在脑磁共振成像中显示小脑深核周围的小脑白质出现T2加权高密度。三名患者的肌肉活检显示出肌病模式和边缘空泡。

对肌肉活检组织的分析表明，LOC642361/NUTM2B-AS1的CGG重复扩展可能会对聚嗜能力产生有害影响，这表明RNA毒性和线粒体功能障碍可能是发病机制之一。因此，这项研究扩展了 LOC642361/NUTM2B-AS1 的 CGG 重复扩增的表型谱，并表明这种基因变异通常表现为眼咽喉肌病，伴有慢性肌病变，肌纤维中有边缘空泡和丝状核内包涵体。

最近发现，LOC642361/NUTM2B-AS1的CGG重复扩增是眼咽远端型肌病伴脑白质病的病因之一。然而，由于仅报道了来自一个家族的三名患者，他们的临床病理特征是否是LOC642361/NUTM2B-AS1中CGG重复扩增的典型特征仍是未知数。

附：英文原文

Title: CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

Author: anonymous

Issue&Volume: 2023/12/29

Abstract: CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with leukoencephalopathy. However, since only three patients from a single family were reported, it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/NUTM2B-AS1. Here, using repeat-primed PCR and long-read sequencing, we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1, typically presenting with oculopharyngodistal myopathy. The CGG repeat expansions range from 161–669 repeat units. Most of the patients present with ptosis, restricted eye movements, dysphagia, dysarthria, and diffuse limb muscle weakness. Only one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance imaging. Muscle biopsies from three patients show a myopathic pattern and rimmed vacuoles. Analyses of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity, suggesting that RNA toxicity and mitochondrial dysfunction may contribute to pathogenesis. Our study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

DOI: 10.1016/j.jgg.2023.12.009

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852723002667