Mutational and clinical spectrum of myofibrillar myopathy in one center from China

Background: Myofibrillar myopathy (MFM) is a heterogeneous group of neuromuscular disorders characterized by degeneration of Z-disk and disintegration of myofibrils. OBJECTIVE: We aimed to analyze the mutational spectrum and phenotypic features of MFM in China. Methods: We used targeted next generation sequencing (NGS) to identify causative mutations in 39 MFM patients with confirmed myopathological diagnosis. Results: The results showed that variants were found in six MFM-associated genes, including DES, FLNC, BAG3, MYOT, TTN and DNAJB6, in 28 (71.7%), 3 (7.7%), 3 (7.7%), 1 (2.6%), 3 (7.7%), and 1 (2.6%), respectively. Of the total 26 variants identified, 19 were reported previously and 7 were novel variants. Missense variant (80.0%) was the most common mutant type of DES. P209L was the hotspot mutation of BAG3 while no obvious hotspot mutation was found of DES. Clinically, distal and proximal weakness were observed in 64.1% and 35.9% patients. Arrythmia and peripheral neuropathy were the most common combined symptoms of desminopathy and BAG3opathy, respectively. Pathologically, rimmed vacuoles (RVs) were present in different genetic type of MFM. Giant axonal nerve fiber was found in BAG3-releated MFM patient. Conlusion: We concluded that MFM showed a highly variable genetic spectrum, with DES as the most frequent causative gene followed by FLNC, BAG3 and TTN. This study expanded the genotypic and phenotypic spectrum of MFM among Chinese cohort.