{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:22:07Z","timestamp":1747149727290,"version":"3.40.5"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["JIMD Reports"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Maple syrup urine disease (MSUD) is a rare autosomal recessive inherited disorder of branched\u2010chain amino acid metabolism caused by mutations in <jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic>, and <jats:italic>DBT<\/jats:italic> that encode the E1\u03b1, E1\u03b2, and E2 subunits of the branched\u2010chain \u03b1\u2010ketoacid dehydrogenase (BCKD) complex. Various MSUD\u2010causing variants have been described; however, no structural rearrangements in <jats:italic>BCKDHA<\/jats:italic> have been reported to cause the classic MSUD phenotype. Here, we describe the classic patient with MSUD with compound heterozygous pathogenic variants in <jats:italic>BCKDHA<\/jats:italic>: a missense variant (NM_000709.3:c.757G\u2009&gt;\u2009A, NP_000700.1:p.Ala253Thr) and a paracentric inversion disrupting Intron 1 of <jats:italic>BCKDHA<\/jats:italic>, which was identified by whole\u2010genome sequencing and validated by fluorescence in situ hybridization. Using the sequence information of the breakpoint junction, we gained mechanistic insight into the development of this structural rearrangement. Furthermore, the establishment of junction\u2010specific polymerase chain reaction could facilitate identification of the variant in case carrier or future prenatal\/preimplantation tests are necessary.<\/jats:p>","DOI":"10.1002\/jmd2.12333","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T00:10:10Z","timestamp":1663719010000},"page":"575-580","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Maple syrup urine disease due to a paracentric inversion of chr 19 that disrupts <scp><i>BCKDHA<\/i><\/scp>: A case report"],"prefix":"10.1002","volume":"63","author":[{"given":"Katsuyuki","family":"Yokoi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake Japan"},{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science, Fujita Health University  Toyoake 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University  Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Tsutsumi","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science, Fujita Health University  Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidehito","family":"Inagaki","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetics Institute for Comprehensive Medical Science, Fujita Health University  Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsushi","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Fujita Health University School of Medicine  Toyoake 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