{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T02:17:42Z","timestamp":1791339462568,"version":"4.3.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,4,24]],"date-time":"2009-04-24T00:00:00Z","timestamp":1240531200000},"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":[[2009,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder that is caused by a deficiency of the enzyme \u03b1\u2010<jats:sc>L<\/jats:sc>\u2010iduronidase (IDUA). Of the 21 Czech and Slovak patients who have been diagnosed with MPS I in the last 30 years, 16 have a severe clinical presentation (Hurler syndrome), 2 less severe manifestations (Scheie syndrome), and 3 an intermediate severity (Hurler\/Scheie phenotype). Mutation analysis was performed in 20 MPS I patients and 39 mutant alleles were identified. There was a high prevalence of the null mutations p.W402X (12 alleles) and p.Q70X (7 alleles) in this cohort. Four of the 13 different mutations were novel: p.V620F (3 alleles), p.W626X (1 allele), c.1727\u2009+\u20092T\u2009&gt;\u2009G (1 allele) and c.1918_1927del (2 alleles). The pathogenicity of the novel mutations was verified by transient expression studies in Chinese hamster ovary cells. Seven haplotypes were observed in the patient alleles using 13 intragenic polymorphisms. One of the two haplotypes associated with the mutation p.Q70X was not found in any of the controls. Haplotype analysis showed, that mutations p.Q70X, p.V620F, and p.D315Y probably have more than one ancestor. Missense mutations localized predominantly in the hydrophobic core of the enzyme are associated with the severe phenotype, whereas missense mutations localized to the surface of the enzyme are usually associated with the attenuated phenotypes. Mutations in the 130 C\u2010terminal amino acids lead to clinical manifestations, which indicates a functional importance of the C\u2010terminus of the IDUA protein. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32812","type":"journal-article","created":{"date-parts":[[2009,4,27]],"date-time":"2009-04-27T22:41:22Z","timestamp":1240872082000},"page":"965-974","source":"Crossref","is-referenced-by-count":29,"title":["Mucopolysaccharidosis type I in 21 Czech and Slovak patients: Mutation analysis suggests a functional importance of C\u2010terminus of the IDUA protein"],"prefix":"10.1002","volume":"149A","author":[{"given":"Alzbeta","family":"Vazna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare","family":"Beesley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Berna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa","family":"Stolnaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Myskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Bouckova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Vlaskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Poupetova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Zeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Magner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hlavata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Winchester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Hrebicek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Dvorakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.1999.6310009.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100606"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705718"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.6.861"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.1380060119"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcped.2007.06.018"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(87)90021-2"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btg430"},{"key":"e_1_2_6_10_1","first-page":"77","volume-title":"Techniques in diagnostic human biochemical genetics: A laboratory manual","author":"Dembure P","year":"1991"},{"key":"e_1_2_6_11_1","first-page":"667","article-title":"Laronidase for treating mucopolysaccharidosis type I","volume":"6","author":"El Dib RP","year":"2007","journal-title":"Genet Mol Res"},{"key":"e_1_2_6_12_1","first-page":"251","article-title":"Development, multiplexing, and application of ARMS tests for common mutations in the CFTR gene","volume":"51","author":"Ferrie RM","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)11:4<332::AID-HUMU16>3.0.CO;2-P"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/17.9.3606"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2004.03.012"},{"key":"e_1_2_6_16_1","first-page":"381","article-title":"The mucopolysaccharidoses. 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