A series of Chinese patients with desminopathy associated with six novel and one reported mutations in the desmin geneAims: Desminopathy is a hereditary cardiac and skeletal myopathy caused by mutations in the desmin gene. This study summarizes the clinical, myopathological and genetic features of a series of Chinese patients with desminopathy. Methods: Thirty-nine cases from five families with autosomal dominant inheritance and two sporadic cases were investigated. 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. 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 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.

Background and purpose Dermatomyositis (DM) with anti‐nuclear matrix protein‐2 (NXP‐2) antibodies usually shows multifocal ischaemic lesions in muscle. Here, we aimed to investigate the microarteriopathy underlying muscle ischaemia in anti‐NXP‐2‐positive DM. Methods A total of 16 patients diagnosed with anti‐NXP‐2‐positive DM were investigated by muscle biopsy. A total of 13 patients with DM with other myositis‐specific antibodies and 11 normal controls were included for comparison. Immunofluorescence assays were performed to localize endothelial cells, smooth muscle cells and pericytes, and to determine lesions in myofibers and microvessels by vascular endothelial growth factor and myxovirus resistance protein A (MxA). Electron microscopy was carried out to assess ultrastructure alterations. Results Subcutaneous edema, severe muscle weakness and dysphagia together with elevated creatine kinase, D‐dimer and triglyceride levels, and decreased albumin levels were found in anti‐NXP‐2‐positive DM. Muscle ischaemia included regional muscle edema, perifascicular atrophy, microinfarcts and focal punched‐out vacuoles. The density of arterioles was higher in anti‐NXP‐2‐positive DM (P ＜ 0.05). Perimysial arterioles with thickened vascular wall, thrombosis and lipid accumulation were found in the vascular wall of diseased perimysial arterioles. The frequency of diseased arterioles and thrombosis was higher in anti‐NXP‐2‐positive DM (P < 0.05). Sarcoplasmic vascular endothelial growth factor and MxA expression was observed in multifocal ischaemic lesions. MxA was present in endothelial and smooth muscle cells of the diseased arterioles and pericytes. Electron microscopy confirmed damaged capillaries and tubuloreticular structures. Conclusions Our research suggested that perimysial arterioles were most commonly involved in anti‐NXP‐2‐positive DM, which led to muscle ischaemia.

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