{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T19:03:47Z","timestamp":1771268627684,"version":"3.50.1"},"reference-count":90,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT","award":["PTDC\/DTP-PIC\/2220\/2014"],"award-info":[{"award-number":["PTDC\/DTP-PIC\/2220\/2014"]}]},{"name":"FCT","award":["NORTE-01-0246-FEDER-000014"],"award-info":[{"award-number":["NORTE-01-0246-FEDER-000014"]}]},{"name":"NORTE2020","award":["PTDC\/DTP-PIC\/2220\/2014"],"award-info":[{"award-number":["PTDC\/DTP-PIC\/2220\/2014"]}]},{"name":"NORTE2020","award":["NORTE-01-0246-FEDER-000014"],"award-info":[{"award-number":["NORTE-01-0246-FEDER-000014"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Mitochondrial diseases are the most common inherited inborn error of metabolism resulting in deficient ATP generation, due to failure in homeostasis and proper bioenergetics. The most frequent mitochondrial disease manifestation in children is Leigh syndrome (LS), encompassing clinical, neuroradiological, biochemical, and molecular features. It typically affects infants but occurs anytime in life. Considering recent updates, LS clinical presentation has been stretched, and is now named LS spectrum (LSS), including classical LS and Leigh-like presentations. Apart from clinical diagnosis challenges, the molecular characterization also progressed from Sanger techniques to NGS (next-generation sequencing), encompassing analysis of nuclear (nDNA) and mitochondrial DNA (mtDNA). This upgrade resumed steps and favored diagnosis. Hereby, our paper presents molecular and clinical data on a Portuguese cohort of 40 positive cases of LSS. A total of 28 patients presented mutation in mtDNA and 12 in nDNA, with novel mutations identified in a heterogeneous group of genes. The present results contribute to the better knowledge of the molecular basis of LS and expand the clinical spectrum associated with this syndrome.<\/jats:p>","DOI":"10.3390\/genes14081536","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T01:56:16Z","timestamp":1690509376000},"page":"1536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Leigh Syndrome Spectrum: A Portuguese Population Cohort in an Evolutionary Genetic Era"],"prefix":"10.3390","volume":"14","author":[{"given":"Manuela Schubert","family":"Baldo","sequence":"first","affiliation":[{"name":"Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal"}]},{"given":"C\u00e9lia","family":"Nogueira","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal"},{"name":"Neonatal Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal"}]},{"given":"Cristina","family":"Pereira","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal"},{"name":"Neonatal Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8985-1156","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Janeiro","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Disease Reference Center, Lisbon North University Hospital Center (CHULN), EPE, 1649-028 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5462-5757","authenticated-orcid":false,"given":"Sara","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Inherited Metabolic Disease Reference Center, Pediatric Hospital, Hospital and University Center of Coimbra, 3004-561 Coimbra, Portugal"}]},{"given":"Charles M.","family":"Louren\u00e7o","sequence":"additional","affiliation":[{"name":"Neurogenetics Department, Faculdade de Medicina de S\u00e3o Jose do Rio Preto, S\u00e3o Jose do Rio Preto 15090-000, Brazil"}]},{"given":"Anabela","family":"Bandeira","sequence":"additional","affiliation":[{"name":"Oporto Hospital Centre, University of Porto, 4099-001 Porto, Portugal"}]},{"given":"Esmeralda","family":"Martins","sequence":"additional","affiliation":[{"name":"Oporto Hospital Centre, University of Porto, 4099-001 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine, Instituto de Ci\u00eancias Biom\u00e9dicas Abel Salazar, Porto University, 4050-313 Porto, Portugal"}]},{"given":"Marina","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Neurology Porto Hospital and University Centre, EPE, 4050-011 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1864-1503","authenticated-orcid":false,"given":"Esmeralda","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Reference Center for Inherited Metabolic Disorders, University Hospital Centre S. Jo\u00e3o, 4200-319 Porto, Portugal"}]},{"given":"Helena","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital Centre, EPE, 4434-502 Vila Nova de Gaia, Portugal"}]},{"given":"Ana Cristina","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hospital D. Estef\u00e2nia, 1169-045 Lisbon, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6186-779X","authenticated-orcid":false,"given":"Laura","family":"Vilarinho","sequence":"additional","affiliation":[{"name":"Research and Development Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal"},{"name":"Neonatal Screening, Metabolism and Genetics Unit, Human Genetics Department, National Institute of Health Doutor Ricardo Jorge, 4000-055 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1002\/ana.24551","article-title":"Leigh Syndrome: One Disorder, More than 75 Monogenic Causes: Leigh Syndrome","volume":"79","author":"Lake","year":"2016","journal-title":"Ann. 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