DNM2 mutations in Chinese Han patients with centronuclear myopathy.

Centronuclear myopathy (CNM) is a congenital myopathy characterized by an abnormally high number of muscle fibers with centrally located nuclei. Autosomal-dominant centronuclear myopathy-1 (CNM1) results from mutations in the dynamin 2 gene (DNM2) and accounts for approximately 50 % of all CNM cases. Up to now, around 35 mutations of DNM2 gene have been identified in CNM; however, the underlying molecular mechanism of DNM2 mutation in the pathology of CNM remains elusive, and the standard clinical characteristics and the genotype-phenotype correlation of DNM2 gene mutation with CNM have not yet been defined. Here, we report the clinical characteristics, molecular diagnosis strategy, and DNM2 gene mutations of four Chinese Han patients with CNM. Congenital myopathy-targeted next-generation sequencing (NGS) was applied to sequence the regions of the genome that contain all the coding regions of all known CNM genes and other congenital myopathy genes. We found potential DNM2 mutations in all four of the patients. Further targeted Sanger DNA sequencing of DNM2 found the 1106G>A (p.R369Q) mutation in patients 1 and 2, the c.1393C>T (p.R465W) mutation in patient 3, and the c.1565G>A (p.R522H) mutation in patient 4, all of which were reported previously to be causative mutations of DNM2-related CNM. Our results suggest that the combination of targeted NGS and Sanger sequencing is an effective, rapid, and reliable strategy for the molecular diagnosis of CNM and other genetically heterogeneous disorders.