Clinico-pathological features and mutational spectrum of 16 nemaline myopathy patients from a Chinese neuromuscular center

Abstract

Nemaline myopathy (NM) is a congenital myopathy of great heterogeneity, characterized by the presence of rods in the cytoplasm of muscle fibers. The samples of 16 nemaline myopathy patients diagnosed by characteristically pathological features went through whole exon sequencing. Clinico-pathological and genetic features of the cases were systematically analyzed. According to the classification of nemaline myopathy by ENMC, 8 cases are typical congenital subtype, 6 cases are childhood/juvenile onset subtype and 2 case are adult onset subtype. In histological findings, characteristic purple-colored rods are discovered under modified gömöri trichrome staining (MGT). Electron microscopy revealed the presence of high electron-dense nemaline bodies around the submucosa and the nucleus nine patients (9/16 56.3%) were detected pathogenic causative mutations, among whom mutations in the NEB gene were the most frequent (6 patients, 66.7%). KBTBD13 gene mutation was discovered in two patients and ACTA1 gene mutation was discovered in 1 patient. Nemaline myopathy is a congenital myopathy with highly clinico-pathological and genetic heterogeneity. NEB gene mutation is the most common mutation, in which splicing change c.21522 +3A > G is hotspot mutation in Chinese NM patients.

Keywords: Clinical features; Gene mutation; Nemaline myopathy; Pathology.

Fig. 1

Histochemical, Ultrastructural findings in the muscle biopsy samples from nemaline myopathy patients (Case 3). HE staining indicates that collection of rods of eosinophilic rods assemble under the sarcolemma of many muscle fiber membranes. (X400, a); MGT staining suggests that typical purple-colored rods are observed in the subsarcolemmal region of muscle fibers. (X400, b); NADH-TR staining shows areas deviod of oxidative enzyme activity in which rods exist. (X400, c); Electron microscopy show rod-like structure with high electron density among myofibrils. (X8000, d); The rod-like structure with high electron density among segments of myofibrils, and the surrounding myofibrillar structure is ruptured. (X15000, e Enlarged figure of d); Electron microscopy show that there are many rod-like structures with different electron densities near the nucleus (X10000, f)