{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:46:17Z","timestamp":1785509177620,"version":"3.56.0"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>\n<jats:italic>LYRM7<\/jats:italic>\u2010associated mitochondrial complex III deficiency has classically been described in the literature as a childhood\u2010onset episodic leukoencephalopathy with neuroimaging findings of cavitating periventricular and subcortical white matter loss. We describe the heterogeneous clinical and neuroimaging profile of six individuals from south India with the specific homozygous pathogenic variant in the <jats:italic>LYRM7<\/jats:italic> gene (c.2T&gt;C, (p.Met1?)). This is a retrospective case series featuring six cases (four pediatric, one adult, and one adolescent\u2010onset) with the pathogenic start loss <jats:italic>LYRM7<\/jats:italic> variant. The spectrum of neurologic manifestations and brain imaging findings documented over multiple clinic visits was analyzed and described. Vision loss and lactic acidosis were seen in all but one individual. A novel phenotype with adult\u2010onset isolated bilateral simultaneous optic neuropathy was noted. Characteristic cavitating leukoencephalopathy in supratentorial white matter was seen in the brain MRI of three out of six individuals. A comprehensive description of our cases along with the previously published cases is provided in the table highlighting the clinical and imaging variability and the disease course. The phenotype of adult\u2010onset isolated acute optic neuropathy can be a manifestation of <jats:italic>LYRM7<\/jats:italic>\u2010related mitochondrial disorder. <jats:italic>LYRM7<\/jats:italic>\u2010associated Mitochondrial Complex III deficiency should be considered in the differential diagnosis of para\u2010 and post\u2010infectious demyelinating\/inflammatory disorders, especially if there is a background of variable developmental delay, recurrence of the episodes, family history, cystic changes in cerebral white matter on imaging, or poor response to immunomodulation. The case series also exemplifies the intra\u2010and inter\u2010familial variability seen with this rare disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.64105","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T08:22:48Z","timestamp":1746174168000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Novel Presentation and Variable Phenotypic Spectrum of Homozygous Start\u2010Loss Variant in <i>LYRM7<\/i>\u2010Associated Mitochondrial Complex III Deficiency"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9000-442X","authenticated-orcid":false,"given":"Noel Deep","family":"Luke","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya","family":"Vijayakrishnan Nair","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajith","family":"Sivadasan","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"Neurology and Clinical Genomics Mayo Clinic  Jacksonville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya Mary","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangeetha","family":"Yoganathan","sequence":"additional","affiliation":[{"name":"Department of Neurological Sciences Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6376-8071","authenticated-orcid":false,"given":"Rekha","family":"Aaron","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anitha","family":"Jasper","sequence":"additional","affiliation":[{"name":"Department of Radio Diagnosis Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavithra","family":"Mannam","sequence":"additional","affiliation":[{"name":"Department of Radio Diagnosis Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6785-915X","authenticated-orcid":false,"given":"Roshan","family":"Daniel","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics KIMS Health Hospital  Trivandrum Kerala India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-370X","authenticated-orcid":false,"given":"Sumita","family":"Danda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Christian Medical College  Vellore Tamil Nadu India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"StatPearls","author":"Ahmad M.","year":"2023"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.11.6196"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63143"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000954"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102615"},{"key":"e_1_2_9_7_1","volume-title":"GeneReviews","author":"Chinnery P. F.","year":"1993"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00441-12"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jimd.12751"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv392"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2015.00134"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22441"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.04.017"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.03.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00933-7"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.12.010"},{"key":"e_1_2_9_17_1","unstructured":"NCBI.2024.\u201cGenes forHomo sapiens(human).\u201dhttps:\/\/www.ncbi.nlm.nih.gov\/datasets\/gene\/id\/90624\/products\/."},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000446586"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2020.101674"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073820904294"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11940\u2010009\u20100046\u20100"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-024-02529-6"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A7097"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.10.005"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-020-00510-6"},{"key":"e_1_2_9_27_1","unstructured":"UniProt. n.d.\u201cUqcrfs1 \u2010 Cytochrome b\u2010c1 Complex Subunit Rieske Mitochondrial \u2013 Mus Musculus (Mouse) | UniProtKB | UniProt.\u201dhttps:\/\/www.uniprot.org\/uniprotkb\/Q9CR68\/entry."},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2019.01.002"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:18:59Z","timestamp":1754903939000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.64105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":27,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/ajmg.a.64105"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.64105","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]},"assertion":[{"value":"2024-10-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e64105"}}