AUTHOR=Luo Yue-Bei , Peng Yuyao , Lu Yuling , Li Qiuxiang , Duan Huiqian , Bi Fangfang , Yang Huan
TITLE=Expanding the Clinico-Genetic Spectrum of Myofibrillar Myopathy: Experience From a Chinese Neuromuscular Center
JOURNAL=Frontiers in Neurology
VOLUME=11
YEAR=2020
URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.01014
DOI=10.3389/fneur.2020.01014
ISSN=1664-2295
ABSTRACT=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.