Expanding the Clinico-Genetic Spectrum of Myofibrillar Myopathy: Experience From a Chinese Neuromuscular Center.

Myofibrillar myopathy is a group of hereditary neuromuscular disorders characterized by dissolution of myofibrils and abnormal intracellular accumulation of Z disc-related proteins. We aimed to characterize the clinical, physiological, pathohistological, and genetic features of Chinese myofibrillar myopathy patients from a single neuromuscular center. A total of 18 patients were enrolled. Demographic and clinical data were collected. Laboratory investigations, electromyography, and cardiac evaluation was performed. Routine and immunohistochemistry stainings against desmin, αB-crystallin, and BAG3 of muscle specimen were carried out. Finally, next-generation sequencing panel array for genes associated with hereditary neuromuscular disorders were performed. Twelve pathogenic variants in , and were identified, of which seven were novel mutations. The novel c.1256C>T substitution is a high frequency mutation. The combined recessively/dominantly transmitted c.19993G>T and c.107545delG mutations in gene cause a limb girdle muscular dystrophy phenotype with the classical myofibrillar myopathy histological changes. We report for the first time that hereditary myopathy with early respiratory failure patient can have peripheral nerve and severe spine involvement. The mutation in Ig-like domain 16 of is associated with the limb girdle type of filaminopathy, and the mutation in Ig-like domain 18 with distal myopathy type. These findings expand the phenotypic and genotypic correlation spectrum of myofibrillar myopathy.