{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:52:26Z","timestamp":1791010346855,"version":"4.1.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"vor","delay-in-days":274,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Biallelic pathogenic\n                    <jats:italic>FDXR<\/jats:italic>\n                    variations were identified in 2017 as being responsible for sensorial neuropathies. The first reported patients suffered from auditory and optic sensorineural impairments (ANOA, MIM #617717). Since then, many publications have described various phenotypes including peripheral and central nervous systems impairments (MMDS9B, MIM #620887). This is consistent with the role of the encoded protein ferredoxin reductase (FDXR) as one of the actors of iron\u2010sulfur proteins synthesis in mitochondria. Ophthalmologic and neurologic symptoms have often been reported, but little is known about the associated inner ear disabilities, although hearing loss was described in the early clinical reports. Firstly, we would like to characterize inner ear abnormalities, sharing our observations of five new patients\u2032 hearing and the outcome after rehabilitation. Thereafter, considering the increasing numbers of publications about\n                    <jats:italic>FDXR<\/jats:italic>\n                    , it appeared useful to provide an overview of literature, analyzing how molecular data may correlate with clinical symptoms. We analyzed the clinical and molecular findings in patients reported from 2017 until March 2025. Data included 89 cases from 79 unrelated families. Protein changes were mostly located in the FAD binding domain, whereas those in NADPH binding domains seem to be less prevalent but more related to severe cases with earlier onset symptoms. These data, combined with current knowledge about FDXR catalytic function and its interaction with FDX and\/or cytochrome P450 proteins, could help to understand potential phenotype\u2010genotype correlations.\n                  <\/jats:p>","DOI":"10.1155\/humu\/5928629","type":"journal-article","created":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T05:53:32Z","timestamp":1791006812000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotype\u2013Phenotype Relationships in Patients Carrying Biallelic\n                    <i>FDXR<\/i>\n                    Pathogenic Variants\u2014New Cases and Systematic Review"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8034-9346","authenticated-orcid":false,"given":"Antoine","family":"Paul","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Bicetre Hospital APHP  Le Kremlin-Bic\u00eatre 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Nevoux","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Bicetre Hospital APHP  Le Kremlin-Bic\u00eatre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-4827","authenticated-orcid":false,"given":"Isabelle","family":"Mosnier","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Auditory Implants Pitie-Salpetriere Hospital AP-HP Sorbonne University  Paris France  sorbonne-universites.fr"},{"name":"Audiology Research Center Pitie-Salpetriere Hospital APHP Paris Cite University Pasteur Institute Inserm CNRS Fondation pour l\u2032audition IHU reConnect  Paris France  cnrs.fr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Rouillon","sequence":"additional","affiliation":[{"name":"Department of Pediatric Otolaryngology Necker-Enfants Malades Hospital APHP  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4635-0658","authenticated-orcid":false,"given":"Yann","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Auditory Implants Pitie-Salpetriere Hospital AP-HP Sorbonne University  Paris France  sorbonne-universites.fr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Benali","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Bicetre Hospital APHP CRMR OPHTARA Paris-Saclay University  Paris France  universite-paris-saclay.fr"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Papon","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Bicetre Hospital APHP  Le Kremlin-Bic\u00eatre 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