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 clinical, muscle biopsy and gene mutation characteristics of nemaline myopathy caused by the NEB gene variants.Methods:A retrospective analysis of the clinical manifestations, auxiliary examinations, muscle biopsies and genetic analysis of 3 nemaline myopathy patients carrying NEB gene mutations diagnosed in the Neuromuscular Pathology Laboratory of Qilu Hospital of Shandong University during 2019-2021 was done. And the related literature was reviewed.Results:All of the 3 patients were congenital onset. The onset symptoms of the 3 patients were weakness of bilateral lower limbs. Physical examinations showed high palatine arches and long narrow faces. Electromyography showed myogenic impairment. Muscle biopsies of the 3 patients revealed myodystrophic changes and nemaline bodies. The ATPase staining of patient 1 showed the predominance and grouping of type 1 muscle fibers. Genetic tests revealed patient 1 carried c.21522+3A>G and c.3471dupC (p.N1158Qfs *5) mutations in the NEB gene, patient 2 carried c.21522+3A>G and c.18991_18992delAG (p.Q6332Afs *8) compound heterozygous mutations and patient 3 carried c.21522+3A>G and c.3448A>T (p.K1150 *) compound heterozygous mutations. All the 3 patients carried the c.21522+3A>G mutation in the NEB gene, which had only been reported in Chinese population. The c.3471dupC (p.N1158Qfs *5), c.18991_18992delAG (p.Q6332Afs *8) and c.3448A>T (p.K1150 *) mutations have not been reported yet. According to American College of Medical Genetics and Genomics guideline, c.21522+3A>G, c.3471dupC (p.N1158Qfs *5), c.3448A>T (p.K1150 *) and c.18991_18992delAG (p.Q6332Afs *8) mutations were all rated pathogenic. Conclusions:The onset age and clinical symptoms of nemaline myopathy are heterogeneous. Muscle biopsy and genetic analysis are important for diagnosis of nemaline myopathy. The c.21522+3A>G mutation in the NEB gene may be more common in Chinese population.