Mutations in heat shock protein B8 were initially identified in inherited neuropathies and were more recently found to cause a predominantly distal myopathy with myofibrillar pathology and rimmed vacuoles. Rare patients also had proximal weakness. Only very few pathogenic variants have been identified in HSPB8. Disruption of the chaperone activity of heat shock protein B8 impairs chaperone-assisted selective autophagy and results in protein aggregation. We report a 23-year-old patient who presented with a 4-year history of predominantly proximal lower limb weakness due to a novel variant in HSPB8. The creatine kinase level was mildly elevated. Electrodiagnostic studies demonstrated a proximal-predominant myopathy without evidence of neuropathy, and muscle histopathology revealed rimmed vacuoles and myofibrillar protein aggregates. Whole exome sequencing identified a de novo frameshift variant in the C-terminal region of HSPB8 (c.577_580dupGTCA, p.Thr194Serfs*23). This case demonstrates that HSPB8-related disorders can present with early onset limb-girdle myopathy without associated neuropathy.

中文翻译：

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HSPB8 C 端区域的一种新的杂合突变导致肢带缘空泡性肌病

热休克蛋白 B8 的突变最初在遗传性神经病中被发现，最近发现主要导致远端肌病，肌原纤维病理和边缘空泡。少数患者也有近端无力。在 HSPB8 中只发现了很少的致病变异。热休克蛋白 B8 分子伴侣活性的破坏会损害分子伴侣辅助的选择性自噬并导致蛋白质聚集。我们报告了一名 23 岁的患者，由于 HSPB8 的一种新变异，他有 4 年的主要近端下肢无力病史。肌酸激酶水平轻度升高。电诊断研究表明近端主要肌病没有神经病变的证据，肌肉组织病理学显示边缘空泡和肌原纤维蛋白聚集体。全外显子组测序在 HSPB8 的 C 端区域发现了一个从头移码变体（c.577_580dupGTCA，p.Thr194Serfs*23）。该病例表明 HSPB8 相关疾病可表现为早发性肢带肌病而无相关神经病变。