{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:54:58Z","timestamp":1753890898790,"version":"3.41.2"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a complex genetic architecture, showing monogenic, oligogenic, and polygenic inheritance. In this study, we describe the case of a 71\u00a0years-old man diagnosed with ALS with atypical clinical features consisting in progressive ocular ptosis and sensorineural deafness. Genetic analyses revealed two heterozygous variants, in the <jats:italic>SOD1<\/jats:italic> (OMIM*147450) and the <jats:italic>TBK1<\/jats:italic> (OMIM*604834) genes respectively, and furthermore mitochondrial DNA (mtDNA) sequencing identified the homoplasmic m.14484T&amp;gt;C variant usually associated with Leber\u2019s Hereditary Optic Neuropathy (LHON). We discuss how all these variants may synergically impinge on mitochondrial function, possibly contributing to the pathogenic mechanisms which might ultimately lead to the neurodegenerative process, shaping the clinical ALS phenotype enriched by adjunctive clinical features.<\/jats:p>","DOI":"10.3389\/fgene.2023.1322067","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T04:36:25Z","timestamp":1702442185000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The genetic puzzle of a SOD1-patient with ocular ptosis and a motor neuron disease: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Veria","family":"Vacchiano","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Palombo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danara","family":"Ormanbekova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Fiorini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessia","family":"Fiorentino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Caporali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Mastrangelo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Lucia","family":"Valentino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Capellari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rocco","family":"Liguori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerio","family":"Carelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/S1474-4422(14)70219-4","article-title":"Analysis of amyotrophic lateral sclerosis as a multistep process: a population-based modelling study","volume":"13","author":"Al-Chalabi","year":"2014","journal-title":"Lancet Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1007\/s00415-022-11355-w","article-title":"Co-occurrence of amyotrophic lateral sclerosis and Leber's hereditary optic neuropathy: is mitochondrial dysfunction a modifier?","volume":"270","author":"Amore","year":"2023","journal-title":"J. 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