CONGENITAL MYOPATHIES: NEMALINE AND TITINOPATHIES: P.231The clinical, genetic, and pathological findings in a Chinese cohort of patients with hereditary nemaline myopathy

Abstract

We aimed to identify the causative mutations of hereditary nemaline myopathy and to investigate the clinical, and pathological features in various genotypes. Methods: We recruited 48 patients with hereditary nemaline myopathy who had been diagnosed by muscle biopsies in our neuromuscular pathology lab from 2007 to 2017. Their clinical data and myopathological findings were retrospectively collected and analyzed. Next generation sequencing was used to identify the causative gene mutations in 40 patients. The onset age of these 48 patients ranged from 0 to 60 years old and the disease course ranged from 2 months to 38 years. Clinically, 23, 14 and 11 patients were typical congenital type, childhood or juvenile onset type and adult onset type, respectively. Molecular genetic analysis in 40 patients revealed possible pathogenic variants in 32 patients (80.00%), including 8 known mutation and 42 novel variants. NEB gene was the most frequent (23 patients, 57.50%), followed by ACTA1 (4 patients, 10.00%), RYR1 (2 patients, 5.00%), KBTBD13 genes (1 patient, 2.50%), TNNT1 (1 patient, 2.50%), and MYO18B (1 patient, 2.50%). Pathologically, thirteen patients showed coexistence of other myopathological features in addition to the presence of nemaline bodies in the muscle fibers, i.e., minicores in 4, cores in 3, central nuclei in 3 and fiber type disproportion in 3 patients. Nemaline bodies were present subsarcolemmally or in the cytoplasm of muscle fibers in patients with NEB mutation. In patients with ACTA1 mutation, nemaline bodies appeared in cluster or as thin filament in the region of disrupted myofibril. In patients with RYR1 mutation, there were rod-like structures formed by distorted Z-discs in the region of disrupted myofibrils. Hereditary nemaline myopathy showed wide clinical and genetic spectrum. Myopathological changes also revealed some difference depending on different genotypes. NEB is the most frequent causative gene in our patient cohort.