{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:05:40Z","timestamp":1789967140781,"version":"4.0.1"},"reference-count":13,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,10,8]],"date-time":"2007-10-08T00:00:00Z","timestamp":1191801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background:<\/jats:title><jats:p>In maple syrup urine disease (MSUD), disease\u2010causing mutations can affect the <jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic> or <jats:italic>DBT<\/jats:italic> genes encoding for the E1\u03b1, E1\u03b2 and E2 subunits of the multienzyme branched\u2010chain 2\u2010keto acid dehydrogenase (BCKD) complex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim:<\/jats:title><jats:p>The aim of this study was to screen DNA samples of 15 subjects with distinct well\u2010characterized variant MSUD phenotypes for mutations in the three genes in order to demonstrate a potential correlation between specific nucleotide changes and particular variant phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>The exonic coding sequences of all three genes were studied using genomic DNA and cellular RNA derived from peripheral blood leukocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>In 37% of the cases (total 30 alleles), disease\u2010causing mutations were located in the <jats:italic>BCKDHA<\/jats:italic>, in 46% in the <jats:italic>BCKDHB,<\/jats:italic> and in 13% in the <jats:italic>DBT<\/jats:italic> gene. Novel mutations occurring homozygously were p.Ala328Thr in the <jats:italic>BCKDHA<\/jats:italic> gene and p.Gly249_Lys257del in the <jats:italic>DBT<\/jats:italic> gene. Both are associated with a mild MSUD variant. The same holds true for the novel mutations p.Pro200Ala in <jats:italic>BCKDHB<\/jats:italic> and p.Phe307Ser in <jats:italic>DBT<\/jats:italic> which were identified in heterozygous fashion. Among the known mutant alleles, p.Gly278Ser in the <jats:italic>BCKDHB<\/jats:italic> gene was relatively frequent and also associated with a mild MSUD variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion:<\/jats:title><jats:p>The results of this study indicate that genotyping may be predictive of clinical severity of variant MSUD phenotypes and might be of prognostic value particularly in subjects with variant MSUD identified in newborn screening in whom early treatment fortunately slows the natural course of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-007-0579-x","type":"journal-article","created":{"date-parts":[[2007,10,5]],"date-time":"2007-10-05T05:23:15Z","timestamp":1191561795000},"page":"903-909","source":"Crossref","is-referenced-by-count":35,"title":["Description of the mutations in 15 subjects with variant forms of maple syrup urine disease"],"prefix":"10.1002","volume":"30","author":[{"given":"N.","family":"Flaschker","sequence":"first","affiliation":[{"name":"Department of General Paediatrics University Children's Hospital Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Feyen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Oncology, Hematology and Clinical Immunology University Children's Hospital Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Fend","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics University Children's Hospital Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics University Children's Hospital Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Schadewaldt","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics University Children's Hospital Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Wendel","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics University Children's Hospital Heinrich\u2010Heine\u2010University D\u00fcsseldorf Germany"},{"name":"Department of General Pediatrics University Children's Hospital D\u00fcsseldorf Moorenstrasse 5 D\u00fcsseldorf D\u201040225 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,10,8]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(00)00105-2"},{"key":"e_1_2_1_3_1","first-page":"1971","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Chuang DT","year":"2001"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117804"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/323677"},{"key":"e_1_2_1_6_1","first-page":"414","article-title":"Occurrence of a 2\u2010bp (AT) deletion allele and a nonsense (G\u2010to\u2010T) mutant allele at the E2 (DBT) locus of six patients with maple syrup urine disease: multiple\u2010exon skipping as a secondary effect of the mutations","volume":"52","author":"Fisher CW","year":"1993","journal-title":"Am J Hum 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