FDXR Mutations Cause Sensorial Neuropathies and Expand the Spectrum of Mitochondrial Fe-S-Synthesis Diseases.

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.

Psychosocial determinants associated with quality of life in people with usher syndrome. A scoping review.

Background: In Usher syndrome, deafness is congenital and blindness is acquired. Therefore, the progressive loss of one of the two senses forces individuals with this syndrome to reorganize their everyday tasks and relationships, creating new strategies to communicate, access information, and move within a given space. This reorganization can interfere with the subjects' capacity to build a good quality of life.Methods: We conducted a scoping review of both peer-reviewed and gray literature, to identify existing evidence of the role of psychosocial determinants on the quality of life of people with Usher syndrome.Results: Twenty-one references met the inclusion criteria. Findings suggest that people with Usher syndrome seem to adjust their life habits to their condition, maintaining hope for the future, and believe in their capacities to accomplish their goals in spite of the various difficulties they encounter. However, this scoping review highlights a lack of research on adaptive strategies, as well as a lack of knowledge concerning the integration of the syndrome in one's identity, the relations to caregivers, and the specificities of the psychotherapeutic support. More information on these topics would enable better-adjusted social, psychotherapeutic, and medical responses.Implications for rehabilitationUsher syndrome, a rare genetic disease, leads to deafblindness, a cluster of related multiple sensory disabilities. People with Usher encounter several obstacles in their daily life. It is also difficult to adapt to the progressive loss of hearing and sight.This paper proposes a scoping review: we identify the main adaptation strategies used by people with Usher Syndrome in order to become autonomous in spite of these obstacles. In becoming more autonomous, they come to a better quality of life.We summarize the most frequent adaptation strategies (at school, work, leisure, interpersonal relationships, etc.) to help programs aimed at rehabilitation for people with Usher syndrome, and to find unexplored research perspectives (e.g., psychotherapies).