{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:20:58Z","timestamp":1790896858022,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2004,12,22]],"date-time":"2004-12-22T00:00:00Z","timestamp":1103673600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2005,1,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Four Dutch male patients, two brothers from unrelated families were referred for investigation of psychomotor and severe language\/speech delay. All four patients showed growth deficiency over the years. Facial features and poor body habitus were quite similar in the patients and in their mothers. Brain MRI showed nonspecific periventricular white matter lesions. In all the patients neuropsychological tests revealed moderate mental retardation, attention deficit and hyperactivity with impulsivity, a semantic\u2010pragmatic language disorder, and oral dyspraxia. This specific cognitive profile is different from other children with mental retardation syndromes and seems to be unique. Excretion of creatine to creatinine ratio in urine of the four boys was increased compared to controls and their creatine uptake in fibroblasts was deficient. In the two brothers from the first pedigree, DNA sequence analysis revealed a novel mutation in the splice donor site in intron 10 (IVS10\u2009+\u20095G&gt;C, c.1495\u2009+\u20095G&gt;C) of the <jats:italic>SLC6A8<\/jats:italic> gene leading to skipping of exon 10. In the other sib pair a novel missense mutation (c. 1361C&gt;T;  p.Pro544Leu) was found. These are the first families reported, in which the clinical suspicion of a creatine transporter disorder was raised on clinical grounds, before a brain <jats:sup>1<\/jats:sup>H\u2010MRS suggested the diagnosis. Screening of apparently X\u2010linked mental retarded patients with this somatic and behavioral phenotype by the biochemical assay of creatine to creatinine ratio in the urine or DNA sequence analysis of <jats:italic>SLC6A8<\/jats:italic> is worthwhile even when <jats:sup>1<\/jats:sup>H\u2010MRS is not available. \u00a9 2004 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.30473","type":"journal-article","created":{"date-parts":[[2004,12,22]],"date-time":"2004-12-22T22:16:59Z","timestamp":1103753819000},"page":"288-295","source":"Crossref","is-referenced-by-count":51,"title":["Two novel mutations in <i>SLC6A8<\/i> cause creatine transporter defect and distinctive X\u2010linked mental retardation in two unrelated Dutch families"],"prefix":"10.1002","volume":"132A","author":[{"given":"G.M.S.","family":"Mancini","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.E.","family":"Catsman\u2010Berrevoets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.F.M.","family":"de Coo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.K.","family":"Aarsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.H.J.","family":"Kamphoven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.G.","family":"Huijmans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Duran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.S.","family":"van der Knaap","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Jakobs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.S.","family":"Salomons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,12,22]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.05.001"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.60.2.268"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10246"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-328X(00)00269-2"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.79"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004728-200301000-00009"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2002-36743"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1086\/340092"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1086\/323765"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.10018"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.WCB.0000033966.83623.7D"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1086\/422102"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/320595"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024405821638"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/318810"},{"key":"e_1_2_7_17_1","first-page":"914","article-title":"Guanidinoacetate methyltransferase deficiency: The first inborn error of creatine metabolism in man","volume":"58","author":"Stockler S","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1024453704800"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0731-7085(98)00280-5"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199912)46:6<925::AID-ANA18>3.0.CO;2-J"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200004)47:4<540::AID-ANA23>3.0.CO;2-K"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.30473","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.30473","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.30473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T19:40:28Z","timestamp":1697658028000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.30473"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,12,22]]},"references-count":20,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2005,1,30]]}},"alternative-id":["10.1002\/ajmg.a.30473"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.30473","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,12,22]]}}}