{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T07:00:09Z","timestamp":1791874809510,"version":"4.3.4"},"reference-count":44,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,1,29]],"date-time":"2007-01-29T00:00:00Z","timestamp":1170028800000},"content-version":"vor","delay-in-days":28,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2007,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mitochondrial complex I deficiency is the commonest diagnosed respiratory chain defect, being genetically heterogeneous. The male preponderance of previous patient cohorts suggested an X\u2010linked underlying genetic defect. We investigated mutations in the X\u2010chromosomal complex I structural genes, <jats:italic>NDUFA1<\/jats:italic> and <jats:italic>NDUFB11<\/jats:italic>, as a novel cause of mitochondrial encephalomyopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We sequenced 12 nuclear genes and the mitochondrial DNA\u2013encoded complex I genes in 26 patients with respiratory chain complex I defect. Novel mutations were confirmed by polymerase chain reaction restriction length polymorphism. Assembly\/stability studies in fibroblasts were performed using two\u2010dimensional blue native gel electrophoresis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Two novel p.Gly8Arg and p.Arg37Ser hemizygous mutations in <jats:italic>NDUFA1<\/jats:italic> were identified in two unrelated male patients presenting with Leigh's syndrome and with myoclonic epilepsy and developmental delay, respectively. Two\u2010dimensional blue native gel electrophoresis showed decreased levels of intact complex I with no accumulation of lower molecular weight subcomplexes, indicating that assembly, stability, or both are compromised.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Mutations in the X\u2010linked <jats:italic>NDUFA1<\/jats:italic> gene result in complex I defect and encephalomyopathy. Assembly\/stability analysis might give an explanation for the different clinical phenotypes and become useful for future diagnostic purposes. Ann Neurol 2007;61:73\u201383<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.21036","type":"journal-article","created":{"date-parts":[[2007,2,2]],"date-time":"2007-02-02T19:02:35Z","timestamp":1170442955000},"page":"73-83","source":"Crossref","is-referenced-by-count":124,"title":["X\u2010linked <i>NDUFA1<\/i> gene mutations associated with mitochondrial encephalomyopathy"],"prefix":"10.1002","volume":"61","author":[{"given":"Daniel","family":"Fernandez\u2010Moreira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Ugalde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roel","family":"Smeets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard J. 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