The majority of patients presented with mild myopathy and prominent cardiomyopathy. Fifteen of 16 deceased cases died of cardiac causes. Of the 25 patients alive, 24 patients developed cardiac abnormalities with disease progression. Muscle specimens from nine patients were investigated in various morphological examinations. Gene sequencing and cell transfections were performed to determine whether the mutant desmin formed intermediate filaments. www.selleckchem.com/products/AG-014699.html Results: Muscle biopsies revealed 5 cases with dystrophy-like patterns and amorphous material
deposits; four other cases showed myopathy-like patterns with cytoplasmic bodies or nemaline bodies. Desmin and multiple proteins aggregated in the affected fibres. Six novel mutations https://www.selleckchem.com/products/Liproxstatin-1.html and one previously reported mutation in the desmin gene were identified in the patients. All the mutant desmin genes except E457V produced multiple desmin-positive clumps or abnormal solid large aggregates in transfected cells. Conclusions: This study enlarges the spectrum of desmin mutations and geographic distribution of desminopathy. Although many novel mutations were identified in Chinese patients, the main clinical and myopathological findings were similar to those in Caucasian patients.
Cardiac conduction abnormalities were prominent and usually appeared later than skeletal myopathy. The myopathology exhibited some heterogeneity among our patients, but the pathological changes were not indicative of the mutation location in the desmin gene. Desmin is a primary element of the intermediate filament network in skeletal, cardiac and smooth muscle cells. Desmin plays a critical role in connecting myofibrils to each other and to the sarcolemma, mitochondria and nuclei from the periphery CYTH4 of the Z line structures . Desmin protein consists of a highly conserved central α-helical rod domain flanked by globular N-terminal head and C-terminal tail domains. The α-helical rod domain of desmin includes four helixes: 1A, 1B, 2A and 2B . Mutations of the
desmin gene, especially in the helix 2B and 1B of the rod domain, are associated with desminopathy [3–5]. Desminopathy is a major subgroup of myofibrillar myopathy, clinically characterized as cardiac and skeletal myopathy [6,7]. Most cases exhibit an autosomal dominant inherited pattern, but autosomal recessive and de novo mutations are also observed [8,9]. Patients usually become symptomatic in the second to the third decade of life. The most typical symptoms manifest as slowly progressive weakness of distal muscles in the lower limbs, later spreading to the upper limbs, neck, trunk and bulbar muscles [3,10]. However, cardiac symptoms may be dominant in some patients [11–13], and are the leading cause of death in most patients [6,14].