{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T15:18:29Z","timestamp":1764688709330},"reference-count":15,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2008,12,16]],"date-time":"2008-12-16T00:00:00Z","timestamp":1229385600000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/22685\/2005"],"award-info":[{"award-number":["SFRH\/BD\/22685\/2005"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2008,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Maple syrup urine disease (MSUD) is a rare disorder of branched\u2010chain amino acid (BCAA) metabolism caused by the defective function of branched\u2010chain \u03b1\u2010ketoacid dehydrogenase complex (BCKD). Many MSUD\u2010causing mutations have already been described in genes that encode the complex (<jats:italic>BCKDHA<\/jats:italic>, <jats:italic>BCKDHB<\/jats:italic> and <jats:italic>DBT<\/jats:italic>), but up to now only four large deletions are known, all located in the <jats:italic>DBT<\/jats:italic> gene. In a previous study we identified a Portuguese MSUD patient with a homozygous deletion of exons 2, 3 and 4 at the <jats:italic>BCKDHA<\/jats:italic> gene; however, the corresponding breakpoints and, consequently, the exact deletion extension were not identified. Here, using long\u2010range PCR and sequencing methodologies we were able to refine the characterization of this gross rearrangement. A genomic DNA loss of about 13.8 kb was detected, starting at intron 1 and ending at intron 4, thus encompassing exons 2, 3 and 4. Molecular characterization showed that the deletion junction contained a short sequence whose motif was CGGG. Since this motif is present in introns 1 and 4 of normal genomic DNA, we have hypothesized that non\u2010homologous recombination was the mechanism underlying the identified large deletion, within which the CGGG could be derived either from intron 1 or from intron 4.<\/jats:p>","DOI":"10.1007\/s10545-008-1046-z","type":"journal-article","created":{"date-parts":[[2008,12,15]],"date-time":"2008-12-15T15:57:44Z","timestamp":1229356664000},"page":"457-460","source":"Crossref","is-referenced-by-count":7,"title":["Maple syrup urine disease due to a new large deletion at <i>BCKDHA<\/i> caused by non\u2010homologous recombination"],"prefix":"10.1002","volume":"31","author":[{"given":"S.","family":"Quental","sequence":"first","affiliation":[{"name":"IPATIMUP \u2013 Institute of Pathology and Molecular Immunology of University of Porto Rua Dr Roberto Frias s\/n Porto 4200\u2010465 Portugal"},{"name":"Faculty of Sciences of University of Porto Porto Portugal"}]},{"given":"E.","family":"Martins","sequence":"additional","affiliation":[{"name":"Children's Hospital Maria Pia Porto Portugal"}]},{"given":"L.","family":"Vilarinho","sequence":"additional","affiliation":[{"name":"Genetics Medical Center INSA Porto Portugal"}]},{"given":"A.","family":"Amorim","sequence":"additional","affiliation":[{"name":"IPATIMUP \u2013 Institute of Pathology and Molecular Immunology of University of Porto Rua Dr Roberto Frias s\/n Porto 4200\u2010465 Portugal"},{"name":"Faculty of Sciences of University of Porto Porto Portugal"}]},{"given":"M.","family":"Jo\u00e3o Prata","sequence":"additional","affiliation":[{"name":"IPATIMUP \u2013 Institute of Pathology and Molecular Immunology of University of Porto Rua Dr Roberto Frias s\/n Porto 4200\u2010465 Portugal"},{"name":"Faculty of Sciences of University of Porto Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2008,12,16]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10254"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9335"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201069"},{"key":"e_1_2_5_5_1","first-page":"1971","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Chuang DT","year":"2001"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119586"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0925-4439(92)90043-M"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.06.007"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04076.x"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.10.4881"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.02.008"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-152827-0.50011-6"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9428"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2003.10.006"},{"key":"e_1_2_5_15_1","unstructured":"SmitAFA HubleyR GreenP(1996\u20132004)RepeatMasker Open\u20103.0. <http:\/\/www.repeatmasker.org>."},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005527731397"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-1046-z","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-008-1046-z","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-008-1046-z","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T04:22:26Z","timestamp":1694751746000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-008-1046-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12]]},"references-count":15,"journal-issue":{"issue":"S2","published-print":{"date-parts":[[2008,12]]}},"alternative-id":["10.1007\/s10545-008-1046-z"],"URL":"https:\/\/doi.org\/10.1007\/s10545-008-1046-z","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12]]}}}