{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:32:24Z","timestamp":1762003944836},"reference-count":26,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2006,10,25]],"date-time":"2006-10-25T00:00:00Z","timestamp":1161734400000},"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":[[2006,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Mucopolysaccharidosis type II (MPS II) is an X\u2010linked recessive lysosomal storage disease caused by a defect in the iduronate\u20102\u2010sulfatase gene (<jats:italic>IDS<\/jats:italic>). Alternative splicing of the <jats:italic>IDS<\/jats:italic> gene can occur and the underlying regulatory mechanism may be rather complex. Nevertheless, little information is available on the role of variations at the <jats:italic>IDS<\/jats:italic> locus in the splicing process. Here we report that splice mutations at the <jats:italic>IDS<\/jats:italic> locus are an important source of MPS II pathogenicity, accounting for almost 56% of Portuguese cases. Among 16 unrelated Portuguese MPS II patients, 15 different mutations were identified: six intronic splice mutations (c.104\u22122AG, c.241\u22122A&gt;G, c.241\u22121G&gt;A, c.418+1G&gt;A, c.880\u22128AG and c.1181\u22121G&gt;C); two exonic splice mutations (c.1006G&gt;lC and c.1122C&gt;T); five missense mutations (D269V, D69V, D148N, R88C and P86L); one nonsense mutation (Q465Ter); one total <jats:italic>IDS<\/jats:italic> gene deletion; and one rearrangement involving a <jats:italic>IDS<\/jats:italic> gene inversion. Furthermore, nine of the 15 detected mutations affected the usual splicing pattern at the locus. Some of them are responsible for dramatic changes in the splicing mechanism. For example, the substitution mutation, c.418+1G&gt;A, revealed the presence of an exonic sequence inside intron 3. Our study provides evidence that the <jats:italic>IDS<\/jats:italic> locus is prone to splicing mutations and that such susceptibility is particularly high in exon 3 and neighbouring regions. Consequently, mutation screening of the <jats:italic>IDS<\/jats:italic> gene cannot be restricted to gDNA examination. Unless cDNA analysis is also conducted, misclassifications as silent or missense mutations can be produced and even uncharacteristic splice\u2010site mutations can be misinterpreted as classic splicing defects that may generate severe, unconventional splicing alterations.<\/jats:p>","DOI":"10.1007\/s10545-006-0403-z","type":"journal-article","created":{"date-parts":[[2006,10,24]],"date-time":"2006-10-24T16:34:12Z","timestamp":1161707652000},"page":"743-754","source":"Crossref","is-referenced-by-count":37,"title":["Molecular characterization of Portuguese patients with mucopolysaccharidosis type II shows evidence that the <i>IDS<\/i> gene is prone to splicing mutations"],"prefix":"10.1002","volume":"29","author":[{"given":"S.","family":"Alves","sequence":"first","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]},{"given":"M.","family":"Mangas","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]},{"given":"M. J.","family":"Prata","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto Porto Portugal"}]},{"given":"G.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]},{"given":"L.","family":"Lopes","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]},{"given":"H.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]},{"given":"J.","family":"Pinto\u2010Basto","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]},{"given":"M. Reis","family":"Lima","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]},{"given":"L.","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Jacinto Magalh\u00e3es Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2006,10,25]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20087"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200213"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1997.0951"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg775"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkg616"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10295"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1048803"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1998.tb02746.x"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb03116.x"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1005432600871"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(199912)14:6<471::AID-HUMU5>3.0.CO;2-5"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9128"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.4.627"},{"key":"e_1_2_1_15_1","first-page":"21","article-title":"Molecular basis of iduronate\u20102\u2010sulphatase gene mutations in patients with mucopolysaccharidosis type II (Hunter syndrome)","volume":"36","author":"Li P","year":"1999","journal-title":"J Med Genet"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20165"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00202-1"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1645"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/16.3.1215"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0004.2001.600412.x"},{"key":"e_1_2_1_21_1","first-page":"2465","volume-title":"The Metabolic and Molecular Bases of Inherited Disease","author":"Neufeld EF","year":"2001"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201044"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh341"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20076"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.3.479"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1406"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/1066527041410418"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-006-0403-z","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-006-0403-z","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-006-0403-z","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T06:19:13Z","timestamp":1694758753000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-006-0403-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,25]]},"references-count":26,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2006,12]]}},"alternative-id":["10.1007\/s10545-006-0403-z"],"URL":"https:\/\/doi.org\/10.1007\/s10545-006-0403-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":[[2006,10,25]]}}}