Department of Neurology, Peking University First Hospital, 100034, Beijing, China.
Department of Neurology, the First Affiliated Hospital of Nanchang University, 330006, Jiangxi, Nanchang, 17 Yongwaizheng Street, China.
Mol Genet Genomic Med. 2023 Jul;11(7):e2176. doi: 10.1002/mgg3.2176. Epub 2023 Mar 31.
The objective of this research was to study the clinical features, genetic characteristics, muscle imaging, and muscle pathological changes of a cohort of Chinese patients with mutations in the valosin-containing protein (VCP) gene.
Nine patients from seven Chinese pedigrees were recruited. Variants were detected by next-generation sequencing and confirmed by Sanger sequencing. Thigh muscle MRIs were performed in five patients. All the patients received muscle biopsies.
Seven variants in VCP were identified, and two were novel. All the patients presented with adult-onset muscle weakness. The appearance of "isolated island sign" or "contra-isolated island sign" was observed in four of the five the patients on muscle MRIs. Muscle biopsies demonstrated the combination of neuropathic and myopathic changes in seven patients and muscle dystrophic changes in two patients. Notably, rimmed vacuoles and cytoplasmic VCP and p62-positive protein aggregates were observed in all the patients.
Our finding of novel variants expanded the mutational spectrum of the VCP gene. This cohort of Chinese patients with VCP mutations mainly present with inclusion body myopathy with predominant limb-girdle distribution. The characteristic pattern of fatty infiltration, especially the "isolated island" and "contra-isolated island" on muscle MRI, along with rimmed vacuoles in muscle biopsy, provides valuable clues for guiding genetic diagnostic workup.
本研究旨在研究携带内含体蛋白（VCP）基因突变的中国患者的临床特征、遗传特征、肌肉影像学和肌肉病理学改变。
招募了来自七个中国家系的九名患者。通过下一代测序检测到变异，并通过 Sanger 测序进行确认。对五名患者进行了大腿肌肉 MRI 检查。所有患者均接受了肌肉活检。
确定了 VCP 中的七个变体，其中两个是新的。所有患者均表现为成年起病的肌肉无力。在五名患者中的四名患者的肌肉 MRI 上观察到“孤立岛征”或“相反孤立岛征”的表现。七名患者的肌肉活检显示神经源性和肌源性改变的组合，两名患者的肌肉活检显示肌肉营养不良改变。值得注意的是，所有患者均观察到边缘空泡和细胞质 VCP 和 p62 阳性蛋白聚集体。
我们发现的新变体扩展了 VCP 基因的突变谱。这组中国 VCP 突变患者主要表现为伴有主要肢体带分布的包涵体肌病。肌肉 MRI 上特征性的脂肪浸润模式，特别是肌肉活检中的“孤立岛”和“相反孤立岛”，以及边缘空泡，为指导遗传诊断工作提供了有价值的线索。
