Case report: Thirty-year progression of an EMPF1 encephalopathy due to defective mitochondrial and peroxisomal fission caused by a novel de novo heterozygous DNM1L variant

Charlène Lhuissier, Bart E. Wagner, Amy Vincent, Gaëtan Garraux, Olivier Hougrand, Rudy Van Coster, Valerie Benoit, Deniz Karadurmus, Guy Lenaers, Naïg Gueguen, Arnaud Chevrollier, Isabelle Maystadt

Résultats de recherche: Contribution à un journal/une revueArticleRevue par des pairs

10 Téléchargements (Pure)


Mutations in DNM1L (DRP1), which encode a key player of mitochondrial and peroxisomal fission, have been reported in patients with the variable phenotypic spectrum, ranging from non-syndromic optic atrophy to lethal infantile encephalopathy. Here, we report a case of an adult female patient presenting with a complex neurological phenotype that associates axonal sensory neuropathy, spasticity, optic atrophy, dysarthria, dysphasia, dystonia, and ataxia, worsening with aging. Whole-exome sequencing revealed a heterozygous de novo variant in the GTPase domain of DNM1L [NM_001278464.1: c.176C>A p.(Thr59Asn)] making her the oldest patient suffering from encephalopathy due to defective mitochondrial and peroxisomal fission-1. In silico analysis suggested a protein destabilization effect of the variant Thr59Asn. Unexpectedly, Western blotting disclosed profound decrease of DNM1L expression, probably related to the degradation of DNM1L complexes. A detailed description of mitochondrial and peroxisomal anomalies in transmission electron and 3D fluorescence microscopy studies confirmed the exceptional phenotype of this patient.

langue originaleAnglais
Numéro d'article937885
journalFrontiers in neurology
Les DOIs
Etat de la publicationPublié - 23 sept. 2022

Contient cette citation