Novel variants, muscle imaging, and myopathological changes in Chinese patients with VCP-related multisystem proteinopathy

ObjectiveThe 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. MethodsNine 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. ResultsSeven 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. ConclusionOur 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.

Automated summary

The study aimed to investigate the clinical features, genetic characteristics, muscle imaging, and muscle pathological changes in Chinese patients with VCP gene mutations. Variants were identified using next-generation sequencing and confirmed with Sanger sequencing. Muscle MRIs showed the presence of isolated island sign or contra-isolated island sign in four out of five patients. Muscle biopsies revealed neuropathic and myopathic changes in seven patients and muscle dystrophic changes in two patients. Rimmed vacuoles and protein aggregates were observed in all patients. The findings expand the mutational spectrum of the VCP gene and provide valuable clues for genetic diagnosis.