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Background: 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. Methods: 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. Results: Twelve pathogenic variants in DES, BAG3, FLNC, FHL1, and TTN were identified, of which seven were novel mutations. The novel DES c.1256C>T substitution is a high frequency mutation. The combined recessively/dominantly transmitted c.19993G>T and c.107545delG mutations in TTN gene cause a limb girdle muscular dystrophy phenotype with the classical myofibrillar myopathy histological changes. Conclusions: 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 FLNC 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.
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[This corrects the article DOI: 10.3389/fneur.2020.01014.].
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Bag3opathy is a rare myofibrillar myopathy (MFM) caused by a mutation in the Bcl-2 associated-athanogene-3 gene. Less than twenty patients have been described, almost all with severe cardiac involvement. We present a 26-year-old man with a c.626C>T (p.Pro209Leu) mutation in the Bcl-2 associated-athanogene-3 gene (BAG3). Our patient presented with problems running before he turned 10 and rapidly progressing, proximal muscle weakness and rigidity of the neck and back. Muscle biopsy showed Z-disc streaming, vacuoles, which is typical findings of Bag3opathy, as well as accumulation of filamentous materials. He rapidly developed respiratory insufficiency necessitating assisted ventilation, and became wheelchair bound by age 13. The progression of his muscle disease is characteristic of Bag3opathy, but unlike other reported cases, he had no evidence of cardiac involvement at age 25 years, despite serial Holter monitoring, ECG and echocardiographs. This case illustrates that counseling of patients with BAG3 myopathy should not predict an inevitable occurrence of cardiomyopathy.