New variant of necklace fibres display peculiar lysosomal structures and mitophagy

Here, we describe a new variant of necklace fibres with specific myopathological features that have not been described thus far. They were observed in two patients, from two independent families with identical DNM2 (dynamin 2) mutation (c.1106 G > A (p.Arg369Gln)), displaying mildly heterogeneous clinical phenotypes. The variant is characterized by lysosomal inclusions, arranged in a necklace pattern, containing homogenous material, devoid of myonuclei. The so-called necklace region has a certain characteristic distance to the sarcolemma. Electron microscopy, including three dimensional reconstructions of serial section images highlights their ultrastructural properties and relation to neighbouring organelles. This new pattern is compared to the previously reported patterns in muscle biopsies containing necklace fibres associated with MTM1- and DNM2-mutations.