Clinical, pathological, and molecular genetic analysis of 7 Chinese patients with hereditary myopathy with early respiratory failure

Hereditary myopathy with early respiratory failure (HMERF) is a subtype of myofibrillar myopathy. Mutations located on exon 344 of the titin-A band, the 119th fibronectin-3 domain (FN3 119), are responsible for HMERF. In this article, we retrospectively analyzed the clinical features, findings of muscle imaging, muscle pathology, immunohistochemistry, and ultrastructural characteristics of seven patients diagnosed with HMERF at a single center in China. Muscle MRI showed the involvement of semitendinosus in four patients. The common pathological features were variability in fiber diameter, increased internal nuclei, endomysial fibrosis, and cytoplasmic bodies. On immunohistochemical examination, the cytoplasmic bodies stained positive for calpain-3, p53, and programmed death-ligand 1. Electron microscopy showed cytoplasmic bodies, distorted sarcomere architecture, glycogen pool, and subsarcolemmal accumulation of mitochondria and lysosomes. We retrospectively reviewed four reported HMERF patients in China. Among the 11 patients, the median age at onset was 34 years (range 14–54). Allelic frequency of mutation c.95195C > T was 36.36%. This study characterizes the phenotype and genotype spectrum of HMERF in China.