A novel DNM2 variant associated with centronuclear myopathy: a case report

Martina Rimoldi ¹ Daniele Velardo ¹ Simona Zanotti ¹ Michela Ripolone ¹ Roberto Del Bo ² Patrizia Ciscato ¹ Laura Maria Napoli ¹ Stefania Corti ² Giacomo Pietro Comi ¹ Dario Ronchi ^2*

• ¹ IRCCS Ca 'Granda Foundation Maggiore Policlinico Hospital, Milan, Lombardy, Italy
• ² University of Milan, Milan, Italy

DNM2 codes for the Dynamin-2 protein, a GTPase involved in clathrin-mediated endocytosis and in other membrane trafficking pathways. The dynamin-2 protein is composed of several functional domains, including a GTPase domain, a middle domain, a pleckstrin homology domain, a GTPase effector domain, and a proline-rich domain.Monoallelic variants in DNM2 are associated with Charcot-Marie-Tooth disease and a rare form of congenital centronuclear myopathy (CNM). Several DNM2 variants have been reported in patients affected with CNM with mild and slowly progressive symptoms.We report the case of a 47-year-old man with DNM2-related myopathy, presenting with progressive muscle weakness since the age of 40 years. Clinical Exome Sequencing revealed the presence of the heterozygous DNM2 variant c.1726G>A, p.(Glu576Lys). This variant, previously unreported, is located in the PH domain of the protein. Muscle biopsy showed several fibers with central nuclei, sometimes multiple. Occasional centronucleated fibers showed a radial distribution of sarcoplasmic strands. This study expands clinical and genetic repertoire of DNM2-related myopathy.