A novel mutation in the DNM2 gene impairs dynamin 2 localization in skeletal muscle of a patient with late onset centronuclear myopathy

作者：Kierdaszuk Biruta; Berdynski Mariusz; Karolczak Justyna; Redowicz Maria Jolanta; Zekanowski Cezary; Kaminska Anna M^*

来源：Neuromuscular Disorders, 2013, 23(3): 219-228.

DOI：10.1016/j.nmd.2012.12.007

• Centronuclear myopathy
• Muscle biopsy
• DNM2 gene
• Dynamin, Myosin VI
• Dystrophin

Centronuclear myopathies constitute a group of heterogeneous congenital myopathies characterized by the presence of abnormal, centrally located nuclei within muscle fibers. Centronuclear myopathies can be caused by mutations of several different genes, including DNM2, encoding dynamin 2 (DNM2) a large GTPase involved in membrane trafficking and endocytosis. We report a 52-year old female with slowly progressive muscle weakness, and a family history of the disease. Clinical, morphological, biochemical and genetic analyses of the proband and her family members were performed, including analyses of the proband%26apos;s muscle biopsy. A novel D614N mutation, located in the C-terminal region pleckstrin-homology (PH) domain of DNM2 was identified in the proband and four family members, who exhibited similar symptoms. The mutation was associated with profound changes in the localization of DNM2 in muscle fibers without significant changes in protein expression. Mutated DNM2 and proteins involved in the membrane trafficking or membrane compartments maintenance were dislocalized within the myofiber, and concentrated at centrally located nuclei. This novel causative mutation (D614N) within the DNM2 gene in a large Polish centronuclear myopathy family with a late age of overt clinical manifestation caused profound changes in DNM2 localization and impaired proper organization of myofibers, and skeletal muscle functioning.

• 出版日期2013-3