ABSTRACT
Objective:To investigate the characteristics of clinical, muscle pathology and gene mutation in patients with nemaline myopathy caused by NEB gene mutation.Methods:The clinical and pathological data of patients with nemaline myopathy caused by NEB gene were collected from Neuromuscular Center of Jiaozuo People′s Hospital from January 1997 to January 2020. The next generation sequencing was preformed to detect NEB gene in all patients, and characteristics of gene mutation were analyzed.Results:Among the 11 patients, there were 8 males and 3 females, and 6 of them came from 2 families. The age of seeing a doctor ranged from 11 to 52 years, the age of onset was from 6 to 23 years, and the course of disease ranged from 5 to 35 years. Neurological examination showed that among the 11 patients, 8 patients had high palatal arch and long face. The muscle tone of both upperlimbs was normal, the tendon reflex was depressed, the proximal muscle strength was grade Ⅲ-Ⅴ, and the distal muscle strength was grade Ⅴ. The muscle tone of both lower extremities was reduced and the tendon reflex was absent. The proximal muscle strength was grade Ⅱ-Ⅳ and the distal muscle strength was grade Ⅲ-Ⅴ. No dysphagia or respiratory muscle involvement was found. Muscle biopsies were performed in 7 of the 11 patients, the pathological changes were muscle fibers of different sizes, circular atrophic muscle fibers and compensatory hypertrophic fibers, and occasionally denatured and necrotic muscle fibers were found. Different degrees of rod aggregation could be seen in all the 7 patients. Electron microscopic examination of 5 patients showed that there was rod aggregation between myofibrils, and most of them were located near the Z band, but no intranuclear rod was found. NEB gene was found in all 11 patients, and a total of 9 different mutation sites were detected, including 8 in exon region and 1 in intron region. Among them, c.21522+3A>G was found in 10 cases, c.1623delT was found in 3 cases and c.17611C>T was found in 3 cases. There was 1 case of c.4417C>T, c.2549delA, c.21065dupA, c.3520G>A, c.20943G>A, c.192G>A respectively.Conclusions:The clinical phenotype of nemaline myopathy caused by NEB gene has great heterogeneity. Muscle pathology shows that rod aggregation is an important basis for the diagnosis of this disease. Mutation c.21522+3A>G in intron is the most common mutation in this group of NEB gene. And the novel mutation sites of NEB gene are respectively c.17611C>T, c.2549delA, c.3520G>A, c.21065dupA, c.20943G>A and c.192G>A.
ABSTRACT
Objective To investigate the effect of methylprednisolone on T helper 17 cell (Th17 cells) related cytokines (interleukin (IL)-23,17A,21,22,6,and tansforming growth factor (TGF)-β) in serum and cerebrospinal fluid from patients with relapsing remitting multiple sclerosis and their effects on the pathogenesis.Methods We recruited relapsing remitting multiple sclerosis group (38 patients)and noninflammatory neurological disease group (20 controls),and detected the levels of IL-23,IL-17A,IL-21,IL-22,TGF-β and IL-6 in serum and cerebrospinal fluid (CSF) with ELISA kit in both controls and patients before and after treatment by methylprednisolone.Results After treatment in relapsing remitting multiple sclerosis patients,IL-17A,IL-23,IL-21,and IL-22 levels in cerebrospinal fluid and serum were significantly decreased,however,they were still higher than that in the non-inflammatory neurological disease patients.TGF-β levels was significantly increased (serum:(17.2 ± 5.9) pg/ml vs (34.1 ± 6.5) pg/ml,t =14.351,P =0.000 ; CSF:(26.4 ± 4.7) pg/ml vs (73.2 ± 19.7) pg/ml,t =16.352,P =0.000).The levels of TGF-β in serum and CSF in patients before treatment were lower than those of in non-inflammatory neurological disease patients (serum:(30.2 ± 8.9) pg/ml,t =6.769,P =0.012 ; CSF:(3 1.4 ± 7.5) pg/ml,t =9.368,P =0.017).However,the levels of TGF-β in CSF in patients after treatment were significantly higher than those in non-inflammatory neurological disease patients (t =9.138,P =0.000).Correlation analysis showed that IL-23 and IL-17A were positive correlation in the serum of relapsing remitting multiple sclerosis patients before treatment.Moreover,positive correlations among IL-23,IL-17A and IL-21 were detected in the CSF of relapsing remitting multiple sclerosis patients before treatment.Conclusions Decreased levels of IL-23,IL-17A,IL-21 and IL-22,and elevated levels of TGF-β were detected in serum and CSF of patients with relapsing remitting multiple sclerosis after methylprednisolone treatment.IL-23,IL-17A,IL-21,IL-22 and TGF-β might involve in the pathogenesis of relapsing remitting multiple sclerosis.