Clinical, muscle pathology and gene mutation characteristics of nemaline myopathy caused by mutations in NEB gene / 中华神经科杂志

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.