Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy

Domenica Immacolata Battaglia, Daniela Martinelli, Adele D'Amico, Daniele Maria Ghezzi, Enrico Silvio Bertini, Daniela Verrigni, Michela Di Nottia, Anna Ardissone, Enrico Baruffini, Alessia Nasca, Andrea Legati, Emanuele Bellacchio, Gigliola Fagiolari, Lucia Fusco, Giulia Trani, Gianmarco Versienti, Silvia Marchet, Alessandra Torraco, Teresa Rizza, Margherita VerardoDaria Diodato, Isabella Moroni, Costanza Lamperti, Stefania Petrini, Maurizio Moggio, Paola Goffrini, Daniele Ghezzi, Rosalba Carrozzo

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


Mitochondria are highly dynamic organelles, undergoing continuous fission and fusion. The DNM1L (dynamin-1 like) gene encodes for the DRP1 protein, an evolutionary conserved member of the dynamin family, responsible for fission of mitochondria, and having a role in the division of peroxisomes, as well. DRP1 impairment is implicated in several neurological disorders and associated with either de novo dominant or compound heterozygous mutations. In five patients presenting with severe epileptic encephalopathy, we identified five de novo dominant DNM1L variants, the pathogenicity of which was validated in a yeast model. Fluorescence microscopy revealed abnormally elongated mitochondria and aberrant peroxisomes in mutant fibroblasts, indicating impaired fission of these organelles. Moreover, a very peculiar finding in our cohort of patients was the presence, in muscle biopsy, of core like areas with oxidative enzyme alterations, suggesting an abnormal distribution of mitochondria in the muscle tissue.
Original languageEnglish
Pages (from-to)601-618
Number of pages18
JournalHuman Mutation
Publication statusPublished - 2019


  • Biomarkers
  • Brain
  • DNA Mutational Analysis
  • DNM1L
  • Dynamins
  • Fibroblasts
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Magnetic Resonance Imaging
  • Mitochondrial Encephalomyopathies
  • Models, Biological
  • Muscles
  • Mutation
  • Protein Conformation
  • Structure-Activity Relationship
  • epileptic encephalopathy
  • mitochondrial disorders
  • mitochondrial dynamics
  • mitochondrial fission
  • muscle biopsy


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