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

Daniela Verrigni, Michela Di Nottia, Anna Ardissone, Enrico Baruffini, Alessia Nasca, Andrea Legati, Emanuele Bellacchio, Gigliola Fagiolari, Diego Martinelli, Lucia Fusco, Domenica Battaglia, Giulia Trani, Gianmarco Versienti, Silvia Marchet, Alessandra Torraco, Teresa Rizza, Margherita Verardo, Adele D'Amico, Daria Diodato, Isabella Moroni & 7 others Costanza Lamperti, Stefania Petrini, Maurizio Moggio, Paola Goffrini, Daniele Ghezzi, Rosalba Carrozzo, Enrico Bertini

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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
Volume40
Issue number5
DOIs
Publication statusPublished - May 1 2019

Fingerprint

Dynamin I
Mitochondria
Muscles
Peroxisomes
Organelles
Dynamins
Brain Diseases
Nervous System Diseases
Fluorescence Microscopy
Virulence
Fibroblasts
Yeasts
Biopsy
Mutation
Mitochondrial encephalopathy
Enzymes
Genes
Proteins

Keywords

  • DNM1L
  • epileptic encephalopathy
  • mitochondrial disorders
  • mitochondrial dynamics
  • mitochondrial fission
  • muscle biopsy

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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title = "Clinical-genetic features and peculiar muscle histopathology in infantile DNM1L-related mitochondrial epileptic encephalopathy",
abstract = "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.",
keywords = "DNM1L, epileptic encephalopathy, mitochondrial disorders, mitochondrial dynamics, mitochondrial fission, muscle biopsy",
author = "Daniela Verrigni and {Di Nottia}, Michela and Anna Ardissone and Enrico Baruffini and Alessia Nasca and Andrea Legati and Emanuele Bellacchio and Gigliola Fagiolari and Diego Martinelli and Lucia Fusco and Domenica Battaglia and Giulia Trani and Gianmarco Versienti and Silvia Marchet and Alessandra Torraco and Teresa Rizza and Margherita Verardo and Adele D'Amico and Daria Diodato and Isabella Moroni and Costanza Lamperti and Stefania Petrini and Maurizio Moggio and Paola Goffrini and Daniele Ghezzi and Rosalba Carrozzo and Enrico Bertini",
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AU - Verrigni, Daniela

AU - Di Nottia, Michela

AU - Ardissone, Anna

AU - Baruffini, Enrico

AU - Nasca, Alessia

AU - Legati, Andrea

AU - Bellacchio, Emanuele

AU - Fagiolari, Gigliola

AU - Martinelli, Diego

AU - Fusco, Lucia

AU - Battaglia, Domenica

AU - Trani, Giulia

AU - Versienti, Gianmarco

AU - Marchet, Silvia

AU - Torraco, Alessandra

AU - Rizza, Teresa

AU - Verardo, Margherita

AU - D'Amico, Adele

AU - Diodato, Daria

AU - Moroni, Isabella

AU - Lamperti, Costanza

AU - Petrini, Stefania

AU - Moggio, Maurizio

AU - Goffrini, Paola

AU - Ghezzi, Daniele

AU - Carrozzo, Rosalba

AU - Bertini, Enrico

PY - 2019/5/1

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