{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:44:17Z","timestamp":1765889057165,"version":"3.41.2"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T00:00:00Z","timestamp":1677196800000},"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. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Maple syrup urine disease (MSUD) is a rare autosomal recessive amino acid metabolic disease. This study is to identify the pathogenic genetic factors of six cases of MUSD and evaluates the application value of high-throughput sequencing technology in the early diagnosis of MUSD.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Clinical examination was carried out for patients and used blood tandem mass spectrometry (MS\/MS), urine gas chromatography-mass spectrometry (GC\/MS), and the application of high-throughput sequencing technology for detection. Validate candidate mutations by polymerase chain reaction (PCR)\u2014Sanger sequencing technology. Bioinformatics software analyzed the variants\u2019 pathogenicity. Using Swiss PDB Viewer software to predict the effect of mutation on the structure of BCKDHA and BCKDHB proteins.<\/jats:p><jats:p><jats:bold>Result:<\/jats:bold> A total of six MSUD patients were diagnosed, including four males and two females. Nine variants were found in three genes of six MSUD families by high-throughput sequencing, including four missense mutations: c.659C&amp;gt;T(p.A220V), c.818C&amp;gt;T(p.T273I), c.1134C&amp;gt;G(p.D378E), and c.1006G&amp;gt;A(p.G336S); two non-sense mutations: c.1291C&amp;gt;T(p.R431*) and c.331C&amp;gt;T(p.R111*); three deletion mutations: c.550delT (p.S184Pfs*46), c.718delC (p.P240Lfs*14), and c.795delG (p.N266Tfs*64). Sanger sequencing\u2019s results were consistent with the high-throughput sequencing. The bioinformatics software revealed that the mutations were harmful, and the prediction results of Swiss PDB Viewer suggest that variation affects protein conformation.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> This study identified nine pathogenic variants in the <jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic>, and <jats:italic>DBT<\/jats:italic> genes in six MSUD families, including two novel pathogenic variants in the <jats:italic>BCKDHB<\/jats:italic> gene, which enriched the genetic mutational spectrum of the disease. High-throughput sequencing is essential for the MSUD\u2019s differential diagnosis, early treatment, and prenatal diagnosis.<\/jats:p>","DOI":"10.3389\/fgene.2023.1132364","type":"journal-article","created":{"date-parts":[[2023,2,24]],"date-time":"2023-02-24T05:07:12Z","timestamp":1677215232000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of gene mutations in six Chinese patients with maple syrup urine disease"],"prefix":"10.3389","volume":"14","author":[{"given":"Lulu","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinmei","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taoyun","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shunan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihe","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuting","family":"Sang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinqi","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifei","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Kong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1007\/s11011-019-00435-y","article-title":"Maple syrup urine disease mutation spectrum in a cohort of 40 consanguineous patients and insilico analysis of novel mutations","volume":"34","author":"Abiri","year":"2019","journal-title":"Metab. 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