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We created the first public locus-specific database (LSDB) dedicated to <jats:italic>ACO2<\/jats:italic> within the \u201cGlobal Variome shared LOVD\u201d using exclusively the Human Phenotype Ontology (HPO), a standard vocabulary for describing phenotypic abnormalities. All the variants and clinical cases listed in the literature were incorporated into the database, from which we produced a dataset. We followed a rational and comprehensive approach based on the HPO thesaurus, demonstrating that <jats:italic>ACO2<\/jats:italic> patients should not be classified separately between isolated and syndromic cases. Our data highlight that certain syndromic patients do not have optic neuropathy and provide support for the classification of the recurrent pathogenic variants c.220C&gt;G and c.336C&gt;G as likely pathogenic. Overall, our data records demonstrate that the clinical spectrum of <jats:italic>ACO2<\/jats:italic> should be considered as a continuum of symptoms and refines the classification of some common variants.<\/jats:p>","DOI":"10.1038\/s41597-021-00984-x","type":"journal-article","created":{"date-parts":[[2021,8,5]],"date-time":"2021-08-05T10:02:50Z","timestamp":1628157770000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["ACO2 clinicobiological dataset with extensive phenotype ontology annotation"],"prefix":"10.1038","volume":"8","author":[{"given":"Khadidja","family":"Guehlouz","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Foulonneau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Amati-Bonneau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Majida","family":"Charif","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estelle","family":"Colin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9line","family":"Bris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Val\u00e9rie","family":"Desquiret-Dumas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Milea","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Gohier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Procaccio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Bonneau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6304-1710","authenticated-orcid":false,"given":"Johan T.","family":"den Dunnen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2736-3349","authenticated-orcid":false,"given":"Guy","family":"Lenaers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0802-4608","authenticated-orcid":false,"given":"Pascal","family":"Reynier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8265-7249","authenticated-orcid":false,"given":"Marc","family":"Ferr\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,5]]},"reference":[{"key":"984_CR1","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1515\/bchm2.1937.247.3.104","volume":"247","author":"C Martins","year":"1937","unstructured":"Martins, C. \u00dcber den Abbau der Citronens\u00e4ure. 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