{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:26:02Z","timestamp":1791815162108,"version":"4.3.4"},"reference-count":21,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T00:00:00Z","timestamp":1563408000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen & Gen Med"],"published-print":{"date-parts":[[2019,9]]},"abstract":"Abstract<\/jats:title>Background<\/jats:title>Mucopolysaccharidosis type I (MPS<\/jats:styled-content> I) is a rare, recessively inherited lysosomal storage disorder, characterized by progressive multi\u2010systemic disease. It is caused by a reduced or absent alpha\u2010l iduronidase (IDUA<\/jats:styled-content>) enzyme activity secondary to biallelic loss\u2010of\u2010function variants in the IDUA<\/jats:styled-content><\/jats:italic>. Over 200 causative variants in IDUA<\/jats:styled-content><\/jats:italic> have been identified. Nevertheless, there is a fraction of MPS<\/jats:styled-content> I patients with only a single mutated IDUA<\/jats:styled-content><\/jats:italic> allele detectable.<\/jats:p><\/jats:sec>Methods<\/jats:title>As genetic testing of MPS<\/jats:styled-content> I is usually based on sequencing methods, copy number variations (CNV<\/jats:styled-content>s) in IDUA<\/jats:styled-content><\/jats:italic> can be missed and therefore presumably remain underdiagnosed. The aim of this study was the detection of CNV<\/jats:styled-content>s using an IDUA<\/jats:styled-content><\/jats:italic>\u2010specific in house<\/jats:italic> multiplex ligation\u2010dependent probe amplification (MLPA<\/jats:styled-content>) assay.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of five unrelated MPS<\/jats:styled-content> I patient samples were re\u2010analyzed after only a single heterozygous IDUA<\/jats:styled-content><\/jats:italic> mutation c.979G>C (p.A327P), c.1469T>C (p.L490P), c.1598C>G (p.P533R), c.1205G>A (p.W402X), c.973\u20107C>G (p.?) could be identified. We detected a novel splice site variant c.973\u20107C>G (p.?), as well as two novel CNV<\/jats:styled-content>s, a large deletion of IDUA<\/jats:styled-content><\/jats:italic> exon 14 and 3\u2019UTR<\/jats:styled-content> c.(1828\u00a0+\u00a01_1829\u20101)_(*1963_?)del, and a large duplication extending from IDUA<\/jats:styled-content><\/jats:italic> exon 2 to intron 12 c.(157\u00a0+\u00a01_158\u20101)_(1727\u00a0+\u00a01_1728\u20101)dup.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Together with the CNV<\/jats:styled-content>s we previously identified, a total of four pathogenic IDUA<\/jats:styled-content><\/jats:italic> CNV<\/jats:styled-content>s have now been reported.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.615","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T20:39:20Z","timestamp":1563482360000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["\u201cMissing mutations\u201d in MPS<\/scp> I: Identification of two novel copy number variations by an IDUA<\/scp><\/i>\u2010specific in house <\/i>MLPA<\/scp> assay"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5967-6732","authenticated-orcid":false,"given":"Amir","family":"Jahic","sequence":"first","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Diagnostics Jena University Hospital Jena Germany"},{"name":"Institute of Laboratory Medicine Clinical Chemistry and Pathobiochemistry Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"G\u00fcnther","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Diagnostics Jena University Hospital Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Muschol","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Hamburg\u2010Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbro","family":"Foss\u00f8y Stadheim","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d8ivind","family":"Braaten","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanne","family":"Kjensli Hyldebrandt","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Oslo University Hospital Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9\u2010Ann","family":"Kuiper","sequence":"additional","affiliation":[{"name":"Pediatric Metabolic Diseases Amsterdam UMC University of Amsterdam Academic Medical Center (AMC) Amsterdam 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