Characterization and genetic diagnosis of centronuclear myopathies in seven Chinese patients

AbstractCentronuclear myopathies (CNMs) are a group of clinically and genetically heterogeneous muscle disorders. Here, we report a cohort of seven CNM patients with their clinical, histological, and morphological features. In addition, using the next-generation sequencing (NGS) technique (5/7 patients), we identified small indels: intronic, exonic, and missense mutations inMTM1,DNM2, andRYR1 genes. Further genetic studies revealed skewed X-chromosome inactivation in two female patients carryingMTM1 mutations. Based on the results of genetic analysis, these seven patients were classified as (1) X-linked recessive myotubular myopathy (patients 1 –3) withMTM1 mutations and mild phenotype, (2) the autosomal dominant CNM (patients 4 –6) withDNM2 mutations, and (3) the autosomal recessive CNM (patient 7) withRYR1 mutations. In all patients, histological findings featured a high proportion of fibers with central nuclei. Radial arrangement of the sarcoplasmic strands was observed inDNM2-CNM andRYR1-CNM patients. Muscle magnetic resonance imaging (MRI) revealed a proximal pattern of involvement presented in bothMTM1-CNM andRYR1-CNM patients. A distal pattern of involvement was present inDNM2-CNM patients. Our findings thereby identified a number of novel features that expand the reported clinicopathological phenotype of CNMs in China.
Source: Neurological Sciences - Category: Neurology Source Type: research