{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T01:08:27Z","timestamp":1781917707992,"version":"3.54.5"},"reference-count":24,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T00:00:00Z","timestamp":1398643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mitochondrial respiratory chain disorder (<jats:styled-content style=\"fixed-case\">MRCD<\/jats:styled-content>) is an intractable disease of infants with variable clinical symptoms. Our goal was to identify the causative mutations in <jats:styled-content style=\"fixed-case\">MRCD<\/jats:styled-content> patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The subjects were 90 children diagnosed with <jats:styled-content style=\"fixed-case\">MRCD<\/jats:styled-content> by enzyme assay. We analyzed whole mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> (mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>) sequences. A cybrid study was performed in two patients. Whole exome sequencing was performed for one of these two patients whose mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> variant was confirmed as non\u2010pathogenic.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Whole mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequences identified 29 mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> variants in 29 patients (13 were previously reported, the other 13 variants and three deletions were novel). The remaining 61 patients had no pathogenic mutations in their mtDNA. Of the 13 patients harboring unreported mtDNA variants, we excluded seven variants by manual curation. Of the remaining six variants, we selected two Leigh syndrome patients whose mitochondrial enzyme activity was decreased in their fibroblasts and performed a cybrid study. We confirmed that m.14439G&gt;A (<jats:italic>MT\u2010ND6<\/jats:italic>) was pathogenic, while m.1356A&gt;G (<jats:italic>mitochondrial 12S rRNA<\/jats:italic>) was shown to be a non\u2010pathogenic polymorphism. Exome sequencing and a complementation study of the latter patient identified a novel c.55C&gt;T hemizygous missense mutation in the nuclear\u2010encoded gene <jats:italic>NDUFA1<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our results demonstrate that it is important to perform whole mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> sequencing rather than only typing reported mutations. Cybrid assays are also useful to diagnose the pathogenicity of mt<jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> variants, and whole exome sequencing is a powerful tool to diagnose nuclear gene mutations as molecular diagnosis can provide a lead to appropriate genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.59","type":"journal-article","created":{"date-parts":[[2014,4,28]],"date-time":"2014-04-28T09:04:40Z","timestamp":1398675880000},"page":"361-369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["New <i>MT\u2010ND6<\/i> and <i>NDUFA1<\/i> mutations in mitochondrial respiratory chain disorders"],"prefix":"10.1002","volume":"1","author":[{"given":"Natsumi","family":"Uehara","sequence":"first","affiliation":[{"name":"Division of Functional Genomics &amp; Systems Medicine Research Center for Genomic Medicine Saitama Medical University Hidaka Japan"},{"name":"Department of Otolaryngology\u2010Head and Neck Surgery Kobe University Graduate School of Medicine Kobe Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Jichi Medical University Shimotsuke Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimi","family":"Tokuzawa","sequence":"additional","affiliation":[{"name":"Division of Functional Genomics &amp; 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