{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:16:40Z","timestamp":1792030600001,"version":"4.4.0"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,7,2]],"date-time":"2019-07-02T00:00:00Z","timestamp":1562025600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013995","name":"Sanofi Genzyme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Mucopolysaccharidosis type I (MPS I) is a rare autosomal recessive disorder resulting from pathogenic variants in the \u03b1\u2010L\u2010iduronidase (\n                    <jats:italic>IDUA<\/jats:italic>\n                    ) gene. Clinical phenotypes range from severe (Hurler syndrome) to attenuated (Hurler\u2010Scheie and Scheie syndromes) and vary in age of onset, severity, and rate of progression. Defining the phenotype at diagnosis is essential for disease management. To date, no systematic analysis of genotype\u2010phenotype correlation in large MPS I cohorts have been performed. Understanding genotype\u2010phenotype is critical now that newborn screening for MPS I is being implemented. Data from 538 patients from the MPS I Registry (380 severe, 158 attenuated) who had 2\n                    <jats:italic>IDUA<\/jats:italic>\n                    alleles identified were examined. In the 1076 alleles identified, 148 pathogenic variants were reported; of those, 75 were unique. Of the 538 genotypes, 147 (27%) were unique; 40% of patients with attenuated and 22% of patients with severe MPS I had unique genotypes. About 67.6% of severe patients had genotypes where both variants identified are predicted to severely disrupt protein\/gene function and 96.1% of attenuated patients had at least one missense or intronic variant. This dataset illustrates a close genotype\/phenotype correlation in MPS I but the presence of unique\n                    <jats:italic>IDUA<\/jats:italic>\n                    missense variants remains a challenge for disease prediction.\n                  <\/jats:p>","DOI":"10.1111\/cge.13583","type":"journal-article","created":{"date-parts":[[2019,6,13]],"date-time":"2019-06-13T10:53:08Z","timestamp":1560423188000},"page":"281-289","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Genotype\u2010phenotype relationships in mucopolysaccharidosis type I (MPS I): Insights from the International MPS I Registry"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0512-7281","authenticated-orcid":false,"given":"Lorne A.","family":"Clarke","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, B.C. Children's Hospital Research Institute University of British Columbia  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[{"name":"Department of Genetics, Federal University of Rio Grande do Sul and Medical Genetics Service Hospital de Cl\u00ednicas de Porto Alegre  Porto Alegre Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Guffon","sequence":"additional","affiliation":[{"name":"Centre de R\u00e9f\u00e9rence des Maladies H\u00e9r\u00e9ditaires du M\u00e9tabolisme H\u00f4pital Femme M\u00e8re Enfant  Bron Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon A.","family":"Jones","sequence":"additional","affiliation":[{"name":"Manchester Centre for Genomic Medicine Manchester University NHS Trust  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillary A.","family":"Keenan","sequence":"additional","affiliation":[{"name":"Sanofi Genzyme  Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria V.","family":"Munoz\u2010Rojas","sequence":"additional","affiliation":[{"name":"Sanofi Genzyme  Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Torayuki","family":"Okuyama","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Viskochil","sequence":"additional","affiliation":[{"name":"University of Utah Salt Lake City  Utah"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chester B.","family":"Whitley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Minnesota  Minneapolis Minnesota"},{"name":"Experimental and Clinical Pharmacology University of Minnesota  Minneapolis Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frits A.","family":"Wijburg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Academic Medical Center  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Muenzer","sequence":"additional","affiliation":[{"name":"University of North Carolina at Chapel Hill  Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,2]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"The Online Metabolic and Molecular Bases of Inherited Disease","author":"Neufeld EF","year":"2014"},{"key":"e_1_2_8_3_1","volume-title":"GeneReviews\u00ae","author":"Clarke LA","year":"1993"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2008-0416"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2007-3847"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-608075"},{"key":"e_1_2_8_7_1","unstructured":"Kunin\u2010BatsonA ShapiroE RudserK et al.Long\u2010term cognitive and functional outcomes in children with mucopolysaccharidosis (MPS)\u2010IH (hurler syndrome) treated with hematopoietic cell transplantation. JIMD Reports2016;29(Chapter 521):1\u20138."},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.11.036"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/apa.14587"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0129-y"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2017.06.048"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13052-018-0552-3"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2018.09.063"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-99"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23301"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21479"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(02)00200-7"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100606"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380060403"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13224"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431-011-1644-x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.01.011"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2014.25"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1357"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1306939110"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0678-1"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2004.12.006"},{"key":"e_1_2_8_28_1","unstructured":"PollardL BraddockS ChristensenK BoylanD HeeseB. Diagnostic follow up of 41 infants with a positive newborn screen for Hurler syndrome (MPSI): identification of four recurrent IDUA sequence changes that significantly reduce enzyme activity. Proceedings of the 2014 APHI newborn screening and genetic testing symposium; October 27\u201030 2014;APHI Annual Meeting Anahein CA.http:\/\/www.aphl.org\/conferences\/proceedings\/Documents\/2014\/NBS\/32Pollard.pdf. Accessed May 2019."}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13583","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13583","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13583","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T10:23:31Z","timestamp":1694255011000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,2]]},"references-count":27,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1111\/cge.13583"],"URL":"https:\/\/doi.org\/10.1111\/cge.13583","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/CGE.13583\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13583\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13583\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13583\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13583\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13583\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/CGE.13583\/v2\/decision1","asserted-by":"object"}]},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,2]]},"assertion":[{"value":"2019-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}