Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report.
Frameshift mutation in SQSTM1 causes proximal myopathy with rimmed vacuoles: A case report.
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DOI：
10.3389/fneur.2023.1043136
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发表时间：
2023
影响因子：
3.4
通讯作者：
中科院分区：
文献类型：
--
作者：
p62/Sequestosome-1（SQSTM 1）是一种应激诱导的支架蛋白，参与多种细胞过程，包括凋亡、炎症、细胞存活和选择性自噬。SQSTM 1突变与一系列多系统蛋白质病相关，包括骨佩吉特病、肌萎缩侧索硬化、额颞叶痴呆和伴有边缘空泡的远端肌病（MRV）。在此，我们报告了一种新的SQSTM 1相关蛋白病表型，一种新的SQSTM 1移码突变导致近端MRV。一名44岁的中国患者表现为进行性肢带无力。她有不对称的近端肢体无力和肌电图的肌病特征。磁共振图像显示脂肪浸润到肌肉中，主要在大腿和内侧腓肠肌中，胫骨前肌除外。肌肉组织病理学显示异常蛋白质沉积，p62/SQSTM 1阳性包涵体和镶边空泡。下一代测序显示了一种新的致病性SQSTM 1移码突变，c.542_549delACAGCCGC（p. H181 Lfs *66）。我们扩展了SQSTM 1的致病基因型，以包括一个新的相关表型：近端MRV。我们建议，SQSTM 1的变化，应在近端MRV的情况下进行筛选。
p62/Sequestosome-1 (SQSTM1) is a stress-inducible scaffold protein involved in multiple cellular processes, including apoptosis, inflammation, cell survival, and selective autophagy. SQSTM1 mutations are associated with a spectrum of multisystem proteinopathy, including Paget disease of the bone, amyotrophic lateral sclerosis, frontotemporal dementia, and distal myopathy with rimmed vacuoles (MRV). Herein, we report a new phenotype of SQSTM1-associated proteinopathy, a novel frameshift mutation in SQSTM1 causing proximal MRV. A 44-year-old Chinese patient presented with progressive limb–girdle weakness. She had asymmetric proximal limb weakness and myopathic features on electromyography. The magnetic resonance images showed fatty infiltration into muscles, predominantly in the thighs and medial gastrocnemius, sparing the tibialis anterior. Muscle histopathology revealed abnormal protein deposition, p62/SQSTM1-positive inclusions, and rimmed vacuoles. Next-generation sequencing showed a novel pathogenic SQSTM1 frameshift mutation, c.542_549delACAGCCGC (p. H181Lfs*66). We expanded the pathogenic genotype of SQSTM1 to include a new, related phenotype: proximal MRV. We suggest that SQSTM1 variations should be screened in cases of proximal MRV.
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