{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:04:25Z","timestamp":1756339465369,"version":"3.44.0"},"reference-count":14,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Case Rep"],"accepted":{"date-parts":[[2025,7,4]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:p>Mutations in the NDUFV1 gene, encoding a subunit of mitochondrial complex I, are typically associated with severe neurological disorders such as Leigh syndrome. We report a pre-teen girl with progressive bilateral optic atrophy and steady visual deterioration, without neurological findings or systemic involvement. Neuroimaging was unremarkable for white matter lesions or structural brain lesions. Whole-exome sequencing demonstrated a homozygous missense mutation (c.1156C&gt;T, p. Arg386Cys) in NDUFV1, implying a nuclear-encoded complex I defect. Laboratory analysis revealed increased lactate levels, consistent with mitochondrial dysfunction. Despite treatment with coenzyme Q, riboflavin and idebenone, no significant visual improvement occurred. This case represents a novel phenotype of NDUFV1-associated disease isolated optic atrophy without systemic involvement expanding the clinical spectrum of NDUFV1 mutations. Recognising this unique mitochondrial optic neuropathy may aid early diagnosis and targeted management.<\/jats:p>","DOI":"10.1136\/bcr-2025-266155","type":"journal-article","created":{"date-parts":[[2025,7,18]],"date-time":"2025-07-18T10:00:24Z","timestamp":1752832824000},"page":"e266155","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["NDUFV1 mutation presenting as isolated progressive optic neuropathy: a unique manifestation of mitochondrial complex I deficiency"],"prefix":"10.1136","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5945-8493","authenticated-orcid":false,"given":"Parul","family":"Mittal","sequence":"first","affiliation":[{"name":"Ophthalmology, All India Institute of Medical Science, Bhopal, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6991-4746","authenticated-orcid":false,"given":"Samendra","family":"Karkhur","sequence":"additional","affiliation":[{"name":"Ophthalmology, All India Institute of Medical Science, Bhopal, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vidhya","family":"Verma","sequence":"additional","affiliation":[{"name":"Ophthalmology, All India Institute of Medical Science, Bhopal, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priti","family":"Singh","sequence":"additional","affiliation":[{"name":"Ophthalmology, All India Institute of Medical Science, Bhopal, Madhya Pradesh, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,7,18]]},"reference":[{"key":"2025082707202534000_18.7.e266155.1","unstructured":"Invernizzi F , D\u2019Amato I , Jensen PB , et al . NDUFV1 mutations in complex I deficiency: Case reports and review of symptoms. J Inherit Metab Dis 2025. Available: https:\/\/pubmed.ncbi.nlm.nih.gov\/34807224\/"},{"key":"2025082707202534000_18.7.e266155.2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1007\/s13258-022-01260-x","article-title":"Compound heterozygous mutations of NDUFV1 identified in a child with mitochondrial complex I deficiency","volume":"44","author":"Tang","year":"2022","journal-title":"Genes Genomics"},{"key":"2025082707202534000_18.7.e266155.3","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv344"},{"key":"2025082707202534000_18.7.e266155.4","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4103\/JPN.JPN_138_17","article-title":"Late-Onset Leigh Syndrome due to NDUFV1 Mutation in a 10-Year-Old Boy Initially Presenting with Ataxia","volume":"13","author":"Incecik","year":"2018","journal-title":"J Pediatr Neurosci"},{"key":"2025082707202534000_18.7.e266155.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2015.01.003"},{"key":"2025082707202534000_18.7.e266155.6","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-018-0209-0"},{"key":"2025082707202534000_18.7.e266155.7","doi-asserted-by":"publisher","DOI":"10.1086\/320603"},{"key":"2025082707202534000_18.7.e266155.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2006.08.007"},{"key":"2025082707202534000_18.7.e266155.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01743.x"},{"key":"2025082707202534000_18.7.e266155.10","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2021.657317","article-title":"Leber\u2019s Hereditary Optic Neuropathy: A Report on Novel mtDNA Pathogenic Variants","volume":"12","author":"Peverelli","year":"2021","journal-title":"Front Neurol"},{"key":"2025082707202534000_18.7.e266155.11","unstructured":"Mochel F , Hainque E , Gras D , et al . Riboflavin in Neurological Diseases: A Narrative Review. Clin Drug Investig 2025. Available: https:\/\/www.springermedicine.com\/link?doi=10.1007\/s40261-021-01038-1"},{"key":"2025082707202534000_18.7.e266155.12","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-pathol-020117-043644","article-title":"Nutritional Interventions for Mitochondrial OXPHOS Deficiencies: Mechanisms and Model Systems","volume":"13","author":"Kuszak","year":"2018","journal-title":"Annu Rev Pathol Mech Dis"},{"key":"2025082707202534000_18.7.e266155.13","unstructured":"Koene S , Smeitink JAM , Beyrath J , et al . Treatment of mitochondrial disorders: antioxidants and beyond. 2025. 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