{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:25:45Z","timestamp":1776990345035,"version":"3.51.4"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100005716","name":"Babol University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016293","name":"University of Mazandaran","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100016293","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Maple syrup urine disease (MSUD; OMIM #248600) is an autosomal recessive metabolic disorder in the catabolism of branched-chain amino acids (leucine, isoleucine, and valine) and may be lethal if untreated in affected newborns.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Single-nucleotide polymorphism haplotyping and Sanger sequencing of BCKDHA, BCKDHB, and DBT genes were performed in a cohort of 10 MSUD patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified a 16.6 Mb homozygous region harboring the DBT gene in an Iranian girl presenting with MSUD. Sanger sequencing revealed a pathogenic homozygous variant (NM_001918.3: c.1174A\u2005&amp;gt;\u2005C) in the DBT gene. We further found a controversial variant (rs12021720: c.1150 A\u2005&amp;gt;\u2005G) in the DBT gene. This substitution (p.Ser384Gly) is highly debated in literature. Bioinformatics and cosegregation analysis, along with identifying the real pathogenic variants (c.1174 A\u2005&amp;gt;\u2005C), lead to terminate these various interpretations of c.1150 A\u2005&amp;gt;\u2005G variant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study introduced c.1150 A\u2005&amp;gt;\u2005G as a polymorphic variant, which is informative for variant databases and also helpful in molecular diagnosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/labmed\/lmac034","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T12:08:09Z","timestamp":1647691689000},"page":"596-601","source":"Crossref","is-referenced-by-count":3,"title":["Pathogenic Homozygous Mutations in the <i>DBT<\/i> Gene (c.1174A&amp;gt;C) Result in Maple Syrup Urine Disease in a rs12021720 Carrier"],"prefix":"10.1093","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0031-4718","authenticated-orcid":false,"given":"Morteza","family":"Alijanpour","sequence":"first","affiliation":[{"name":"Non-Communicable Pediatric Disease Research Center, Health Research Institute, Babol University of Medical Science , Babol , Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4054-1704","authenticated-orcid":false,"given":"Omid","family":"Jazayeri","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, Faculty of Science, University of Mazandaran , Babolsar , Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shima","family":"Soleimani Amiri","sequence":"additional","affiliation":[{"name":"Razi Pathobiology and Genetic Diagnostic Laboratory, Babol , Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-4010","authenticated-orcid":false,"given":"Erwin","family":"Brosens","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Erasmus MC \u2013 Sophia Children\u2019s Hospital , Rotterdam , Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"2022110311282242700_CIT0001","first-page":"39","article-title":"The genes responsible for maple syrup urine disease, molecular pathomechanisms, and causative mutations in Iranian population","volume":"20","author":"Gorjizadeh","year":"2018","journal-title":"J Babol Univ Med Sci."},{"key":"2022110311282242700_CIT0002","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1172\/JCI119586","article-title":"E2 transacylase-deficient (type II) maple syrup urine disease. Aberrant splicing of E2 mRNA caused by internal intronic deletions and association with thiamine-responsive phenotype","volume":"100","author":"Chuang","year":"1997","journal-title":"J Clin Invest."},{"key":"2022110311282242700_CIT0003","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1007\/s12519-020-00349-1","article-title":"Identification of eight novel mutations in 11 Chinese patients with maple syrup urine disease","volume":"16","author":"Sun","year":"2020","journal-title":"World J Pediatr."},{"key":"2022110311282242700_CIT0004","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.ymgme.2008.02.008","article-title":"Molecular and structural analyses of maple syrup urine disease and identification of a founder mutation in a Portuguese Gypsy community","volume":"94","author":"Quental","year":"2008","journal-title":"Mol Genet Metab."},{"key":"2022110311282242700_CIT0005","article-title":"Incidence of maple syrup urine disease in infants 2007\u20132017, Babol, Mazandaran. Do we have founder effect?","author":"Gorgizadeh"},{"key":"2022110311282242700_CIT0006","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1016\/j.ejpn.2015.07.009","article-title":"Evolution of maple syrup urine disease in patients diagnosed by newborn screening versus late diagnosis","volume":"19","author":"Couce","year":"2015","journal-title":"Eur J Paediatr Neurol."},{"key":"2022110311282242700_CIT0007","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1007\/s10545-007-0579-x","article-title":"Description of the mutations in 15 subjects with variant forms of maple syrup urine disease","volume":"30","author":"Flaschker","year":"2007","journal-title":"J Inherit Metab Dis."},{"key":"2022110311282242700_CIT0008","first-page":"97","article-title":"Molecular genetics of maple syrup urine disease in the Turkish population","volume":"51","author":"Gorzelany","year":"2009","journal-title":"Turk J 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Dis."},{"key":"2022110311282242700_CIT0012","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.mgene.2018.01.010","article-title":"Frequent novel mutations are causative for maple syrup urine disease from Southwest Iran","volume":"16:","author":"Sedaghat","year":"2018","journal-title":"Meta Gene."},{"key":"2022110311282242700_CIT0013","doi-asserted-by":"crossref","first-page":"e00606","DOI":"10.1002\/mgg3.606","article-title":"Genetics and genomic medicine in Iran","volume":"7","author":"Behnam","year":"2019","journal-title":"Mol Genet Genomic Med."},{"key":"2022110311282242700_CIT0014","doi-asserted-by":"crossref","first-page":"D886","DOI":"10.1093\/nar\/gky1016","article-title":"CADD: predicting the deleteriousness of variants throughout the human genome","volume":"47","author":"Rentzsch","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"2022110311282242700_CIT0015","doi-asserted-by":"crossref","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 Brain Dis."},{"key":"2022110311282242700_CIT0016","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1515\/jpem-2017-0305","article-title":"Four novel mutations of the BCKDHA, BCKDHB and DBT genes in Iranian patients with maple syrup urine disease","volume":"31","author":"Zeynalzadeh","year":"2018","journal-title":"J Pediatr Endocrinol Metab."},{"key":"2022110311282242700_CIT0017","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."}],"container-title":["Laboratory 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