%0 Journal Article
%T FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases
%A Agn¨¨s Delahodde
%A Agn¨¨s R£¿tig
%A Anthony Drecourt
%A Antoine Paul
%A Christelle Domange
%A Christelle Vasnier
%A Christine Bole-Feysot
%A Crystel Bonnet
%A C¨¦cile Masson
%A Delphine Dupin Deguine
%A Didier Bouccara
%A Fanny Mochel
%A Floriane Petit
%A Georges Challe
%A Ines Ben Aissa
%A Isabelle Mosnier
%A Josseline Kaplan
%A Laurence Jonard
%A Laurence Mahieu
%A Myriam Oufadem
%A Olivier Sterkers
%A Oriane Mercati
%A Patrick Nitschke
%A Saber Masmoudi
%A Souad Gherbi
%A Stanislas Lyonnet
%A Sylvie Gerber
%J Archive of "American Journal of Human Genetics".
%D 2017
%R 10.1016/j.ajhg.2017.09.007
%X Hearing loss and visual impairment in childhood have mostly genetic origins, some of them being related to sensorial neuronal defects. Here, we report on eight subjects from four independent families affected by auditory neuropathy and optic atrophy. Whole-exome sequencing revealed biallelic mutations in FDXR in affected subjects of each family. FDXR encodes the mitochondrial ferredoxin reductase, the sole human ferredoxin reductase implicated in the biosynthesis of iron-sulfur clusters (ISCs) and in heme formation. ISC proteins are involved in enzymatic catalysis, gene expression, and DNA replication and repair. We observed deregulated iron homeostasis in FDXR mutant fibroblasts and indirect evidence of mitochondrial iron overload. Functional complementation in a yeast strain in which ARH1, the human FDXR ortholog, was deleted established the pathogenicity of these mutations. These data highlight the wide clinical heterogeneity of mitochondrial disorders related to ISC synthesis
%K Auditory neuropathy
%K optic atrophy
%K iron-sulfur cluster
%K FDXR
%K ARH1
%K Fe-S cluster synthesis
%K mitochondria
%K iron overload
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5630197/