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Clinical‐genetic features and peculiar muscle histopathology in infantile DNM1L ‐related mitochondrial epileptic encephalopathy
Author(s) -
Verrigni Daniela,
Di Nottia Michela,
Ardissone Anna,
Baruffini Enrico,
Nasca Alessia,
Legati Andrea,
Bellacchio Emanuele,
Fagiolari Gigliola,
Martinelli Diego,
Fusco Lucia,
Battaglia Domenica,
Trani Giulia,
Versienti Gianmarco,
Marchet Silvia,
Torraco Alessandra,
Rizza Teresa,
Verardo Margherita,
D'Amico Adele,
Diodato Daria,
Moroni Isabella,
Lamperti Costanza,
Petrini Stefania,
Moggio Maurizio,
Goffrini Paola,
Ghezzi Daniele,
Carrozzo Rosalba,
Bertini Enrico
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23729
Subject(s) - biology , dnm1l , mitochondrial fission , mitochondrion , dynamin , peroxisome , organelle , microbiology and biotechnology , genetics , gene , endocytosis , cell
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.