{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T02:57:12Z","timestamp":1761101832645},"reference-count":0,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,8,15]],"date-time":"2007-08-15T00:00:00Z","timestamp":1187136000000},"content-version":"vor","delay-in-days":14,"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":[[2007,8]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Cystinuria is an autosomal recessive disorder caused by defective transport of cystine and the dibasic amino acids ornithine, lysine and arginine across cell membranes. Poor solubility of cystine in urine leads to kidney stones and associated symptoms and complications. Mutations of genes <jats:italic>SLC3A1<\/jats:italic> and <jats:italic>SLC7A9<\/jats:italic> encoding for amino acid transport systems are responsible for different types of cystinuria. In this study we describe a new LC\u2010MS\/MS assay for these amino acids in urine. Moreover, we report a novel splice\u2010acceptor site mutation in the <jats:italic>SLC7A9<\/jats:italic> gene that we believe is the cause of the phenotype observed in four siblings from a first\u2010cousin marriage. Into the wells of a 96\u2010well microtitre plate, 10 \u03bcl of urine was mixed with 90 \u03bcl of a solution containing [<jats:sup>2<\/jats:sup>H<jats:sub>4<\/jats:sub>]cystine, [<jats:sup>2<\/jats:sup>H<jats:sub>2<\/jats:sub>]ornithine, [<jats:sup>13<\/jats:sup>C,<jats:sup>2<\/jats:sup>H<jats:sub>4<\/jats:sub>]arginine and [<jats:sup>2<\/jats:sup>H<jats:sub>5<\/jats:sub>]glutamine that was used as an internal standard for lysine. Chromatographic separation was achieved isocratically and detection was in the selected\u2010reaction monitoring mode. The injection\u2010to\u2010injection time was 8 min. Calibration curves were linear up to 1000 \u03bcmol\/L. Intra\u2010day (<jats:italic>n<\/jats:italic>\u2009=\u200910) and inter\u2010day (<jats:italic>n<\/jats:italic>\u2009=\u20096) variations (750 and 10 \u03bcmol\/L) were less than 11.4%. Urine samples from healthy individuals (<jats:italic>n<\/jats:italic>\u2009=\u2009135) were analysed and age\u2010matched reference ranges were generated. The method was applied retrospectively and prospectively to analyse samples (<jats:italic>n<\/jats:italic>\u2009=\u200913) from nine cystinuria patients. The mutation reported here was not found in 100 controls with similar ethnicity to the studied family and is believed to have consequences for the transcribed mature RNA and protein structure and function.<\/jats:p>","DOI":"10.1007\/s10545-007-0670-3","type":"journal-article","created":{"date-parts":[[2007,8,15]],"date-time":"2007-08-15T08:46:11Z","timestamp":1187167571000},"page":"611-611","source":"Crossref","is-referenced-by-count":11,"title":["LC\u2010MS\/MS determination of dibasic amino acids for the diagnosis of cystinuria. Application in a family affected by a novel splice\u2010acceptor site mutation in the <i>SLC7A9<\/i> gene"],"prefix":"10.1002","volume":"30","author":[{"given":"O. Y.","family":"Al\u2010Dirbashi","sequence":"first","affiliation":[{"name":"National Laboratory for Newborn Screening King Faisal Specialist Hospital and Research Centre PO Box 3354 Taksussi Road Riyadh 11211 Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. K.","family":"Abu\u2010Amero","sequence":"additional","affiliation":[{"name":"Department of Genetics King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. F.","family":"Alswaid","sequence":"additional","affiliation":[{"name":"Department of Pediatrics King Abdulaziz Medical City Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"University Children's Hospital Heidelberg University Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Al\u2010Qahtani","sequence":"additional","affiliation":[{"name":"National Laboratory for Newborn Screening King Faisal Specialist Hospital and Research Centre PO Box 3354 Taksussi Road Riyadh 11211 Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. S.","family":"Rashed","sequence":"additional","affiliation":[{"name":"National Laboratory for Newborn Screening King Faisal Specialist Hospital and Research Centre PO Box 3354 Taksussi Road Riyadh 11211 Saudi Arabia"},{"name":"Department of Genetics King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia"},{"name":"Department of Medical Genetics King Faisal Specialist Hospital and Research Centre Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2007,8,15]]},"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-007-0670-3","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-007-0670-3","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T04:34:22Z","timestamp":1694752462000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-007-0670-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,8]]},"references-count":0,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2007,8]]}},"alternative-id":["10.1007\/s10545-007-0670-3"],"URL":"https:\/\/doi.org\/10.1007\/s10545-007-0670-3","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,8]]}}}