{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T01:47:41Z","timestamp":1791856061246,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T00:00:00Z","timestamp":1620259200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disorder caused by the deficient activity of the branched\u2010chain \u03b1\u2010keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by four genes: <jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic>, <jats:italic>DBT<\/jats:italic>, and <jats:italic>DLD<\/jats:italic>. MSUD is predominantly caused by mutations in the <jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic>, and <jats:italic>DBT<\/jats:italic> genes which encode the E1\u03b1, E1\u03b2, and E2 subunits of the BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD in a cohort of Chilean MSUD patients by identifying point mutations in the <jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic>, and <jats:italic>DBT<\/jats:italic> genes and to describe their impact on the phenotypic heterogeneity of these patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This manuscript describes a cross\u2010sectional study of 18 MSUD patients carried out using PCR and DNA sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four novel pathogenic mutations were identified: one in <jats:italic>BCKDHA<\/jats:italic> (p.Thr338Ile), two in <jats:italic>BCKDHB<\/jats:italic> (p.Gly336Ser e p.Pro240Thr), and one in <jats:italic>DBT<\/jats:italic> (p.Gly406Asp). Four additional pathogenic mutations found in this study have been described previously. There were no correlations between the genotype and phenotype of the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>If MSUD is diagnosed earlier, with a newborn screening approach, it might be possible to establish genotype\u2010phenotype relationships more efficiently.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1616","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T04:07:36Z","timestamp":1620360456000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Molecular basis of various forms of maple syrup urine disease in Chilean patients"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2608-9897","authenticated-orcid":false,"given":"Diana Ruffato Resende","family":"Campanholi","sequence":"first","affiliation":[{"name":"Pediatrics Department, Ribeir\u00e3o Preto Medical School University of S\u00e3o Paulo 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