{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T14:27:24Z","timestamp":1771856844569,"version":"3.50.1"},"reference-count":14,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bartim\u00e9us Fonds, The Netherlands","award":["1219277"],"award-info":[{"award-number":["1219277"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Inherited optic neuropathies (IONs) are rare genetic diseases characterized by progressive visual loss due the atrophy of optic nerves. The standard diagnostic workup involving next-generation sequencing panels has a diagnostic yield of about forty percent. In the other 60% of the patients with a clinical diagnosis of ION, the underlying genetic variants remain unknown. In this case study, we describe a potentially new disease-associated gene, NSUN3, for IONs. The proband was a young woman with consanguineous parents. She presented with bilateral optic atrophy and nystagmus at the age of seven years. Genetic testing revealed the homozygous variant c.349_352dup p.(Ala118Glufs*45) in NSUN3, with a segregation in the family compatible with autosomal recessive inheritance. Additional functional analysis showed decreased NSUN3 mRNA levels, slightly diminished mitochondrial complex IV levels, and decreased cell respiration rates in patient fibroblasts compared to healthy controls. In conclusion, pathogenic variants in NSUN3 can cause optic neuropathy. Trio whole-exome sequencing should be considered as a diagnostic strategy in ION cases where standard diagnostic analysis does not reveal disease-causing variants.<\/jats:p>","DOI":"10.3390\/genes15050530","type":"journal-article","created":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T03:56:31Z","timestamp":1713930991000},"page":"530","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Mutations in NSUN3, a Mitochondrial Methyl Transferase Gene, Cause Inherited Optic Neuropathy"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0161-5851","authenticated-orcid":false,"given":"Cansu","family":"de Muijnck","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Department of Ophthalmology, Amsterdam University Medical Centers, Location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-0067","authenticated-orcid":false,"given":"Jacoline B. ten","family":"Brink","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Section Ophthalmogenetics, Amsterdam University Medical Centers, Location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugoline G.","family":"de Haan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Amsterdam University Medical Centers, Location VU, 1081 HV Amsterdam, The Netherlands"},{"name":"Amsterdam Reproduction and Development Research Institute, Amsterdam University Medical Centers, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5227-3527","authenticated-orcid":false,"given":"Richard J.","family":"Rodenburg","sequence":"additional","affiliation":[{"name":"Radboud Center for Mitochondrial Medicine, Departments of Pediatrics and Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1721-0728","authenticated-orcid":false,"given":"Nicole I.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Department of Child Neurology, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, Location VU, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur A.","family":"Bergen","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Section Ophthalmogenetics, Amsterdam University Medical Centers, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Emma Centre for Precision Medicine, Amsterdam University Medical Centers, Location AMC, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camiel J. F.","family":"Boon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Amsterdam University Medical Centers, Location AMC, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Ophthalmology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9286-8397","authenticated-orcid":false,"given":"Maria M.","family":"van Genderen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands"},{"name":"Bartim\u00e9us Diagnostic Center for Complex Visual Disorders, 3703 AJ Zeist, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/ng.3354","article-title":"Mutations in SLC25A46, encoding a UGO1-like protein, cause an optic atrophy spectrum disorder","volume":"47","author":"Abrams","year":"2015","journal-title":"Nat. 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