{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T06:53:53Z","timestamp":1774853633178,"version":"3.50.1"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"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. Neurol."],"abstract":"<jats:p>\n                    Leigh syndrome (LS) is the most common pediatric mitochondrial disorder, typically presenting in infancy with developmental regression, neurological dysfunction, and characteristic brain MRI lesions. It is linked to over 110 genes affecting cellular energy production, making it highly genetically heterogeneous, with complex I deficiency being the most frequent cause. Biallelic mutations in\n                    <jats:italic>NDUFAF6<\/jats:italic>\n                    \u2014a key assembly factor of complex I\u2014cause autosomal recessive Leigh syndrome, specifically NDUFAF6-related Leigh syndrome, also designated as mitochondrial complex I deficiency, nuclear type 17 (MC1DN17; OMIM 618239). Herein, we describe two patients with biallelic loss-of-function variants in\n                    <jats:italic>NDUFAF6<\/jats:italic>\n                    . Patient 1 was homozygous for an in-frame duplication (c.362_364dupTGG; p. Val121dup), whereas patient 2 carried this duplication in trans with a novel frameshift variant (c.169_190dup; p. Leu64fs*2). Both patients manifested motor deterioration, dystonia, dysphagia, and elevated blood lactate levels during infancy, along with symmetrical basal ganglia necrosis on brain MRI. A retrospective analysis of all 24 MC1DN17 cases confirmed infantile\/childhood onset, psychomotor regression, dystonia, bilateral striatal necrosis with additional features, and hyperlactataemia as universal characteristics. Mortality was low (1\/24; 4%), with motor function maintained for longer than in some other LS-associated genetic subtypes. No clear genotype\u2013phenotype correlation was identified, and disease progression remains difficult to predict. There are currently no disease-modifying treatments available; only supportive care can be provided. Our study expands the\n                    <jats:italic>NDUFAF6<\/jats:italic>\n                    mutational spectrum and consolidates its distinct clinical profile, highlighting the need for long-term data to define natural history and guide therapy.\n                  <\/jats:p>","DOI":"10.3389\/fneur.2026.1778719","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:27:00Z","timestamp":1774848420000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and genetic analysis of Chinese patients with Leigh syndrome caused by biallelic loss-of-function variants of the NDUFAF6 gene"],"prefix":"10.3389","volume":"17","author":[{"given":"Qi","family":"Yang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xunzhao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zailong","family":"Qin","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuanjing","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shujie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiliang","family":"Lu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shang","family":"Yi","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingsi","family":"Luo","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Birth Defects Research and Prevention, Guangxi Key Laboratory of Reproductive Health and Birth Defects Prevention, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Department of Genetic and Metabolic Central Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]},{"name":"Guangxi Clinical Research Center for Pediatric Diseases, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1002\/ana.75","article-title":"The incidence of mitochondrial encephalomyopathies in childhood: clinical features and morphological, biochemical, and DNA abnormalities","volume":"49","author":"Darin","year":"2001","journal-title":"Ann Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1002\/ana.410390311","article-title":"Leigh syndrome: clinical features and biochemical and DNA abnormalities","volume":"39","author":"Rahman","year":"1996","journal-title":"Ann 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