P.4.5 Muscle NMR imaging in the rare E650K mutation in the DNM2 gene in a centronuclear myopathy patient

Abstract

Autosomal dominant centronuclear myopathy (CNM) is characterized by slowly progressive muscular weakness and wasting, and high frequency of centrally located nuclei in muscle fibers. The disorder involves mainly limb girdle, trunk and neck muscles but may also affect distal muscles. Ptosis and limitation of eye movements are frequent. Molecular analysis has identified recurrent mutations in exons 8 and 11 and rare heterozygous missense mutations in the dynamin-2 (DNM2) gene, which encodes a protein involved in endocytosis and membrane trafficking, actin assembly, and centrosome cohesion. We recently identified an isolated case of a 34 years old male patient, complaining of gait difficulties since the age of 14 years. Two years ago, the condition evolved to limb muscle weakness due to a predominantly distal severe lower limbs muscle atrophy associated to pes cavus. He also presented mild facial weakness with a discrete ptosis without ophtalmoparesis. By sequencing DNM2 exons, we found the rare heterozygous missense mutation c.1948G > A (p.E650K) in the DNM2 gene. This mutation was only described in one Chilean family. T1-weighted whole-body NMR imaging revealed fatty degenerative changes predominantly affecting the legs (score of 3 in a scale of 4), the face and the thighs. Thigh muscle displayed the particular reticular-punctuated pattern of fatty infiltration seen in CNM patients. The pattern of lesion distribution and the particular muscle texture observed in this patient are highly evocative of the disease. Therefore, NMR findings are showing comparable alterations in DNM2-related CNM patients, independently of the pathogenic mutation. FAPESP-CEPID, CNPQ-INCT, FINEP, CAPES-COFECUB.