{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T02:16:37Z","timestamp":1792030597873,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Develop Med Child Neuro"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Mucopolysaccharidosis type <jats:styled-content style=\"fixed-case\">II<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">MPS II<\/jats:styled-content>) is caused by variants in the iduronate\u20102\u2010sulphatase gene (<jats:italic><jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content><\/jats:italic>). Patients can be either neuronopathic with intellectual disability, or non\u2010neuronopathic. Few studies have reported on the <jats:italic><jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content><\/jats:italic> genotype\u2013phenotype relationship and on the molecular effects involved. We addressed this in a cohort study of Dutch patients with <jats:styled-content style=\"fixed-case\">MPS II<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Intellectual performance was assessed for school performance, behaviour, and intelligence. Urinary glycosaminoglycans were quantified by mass spectrometry. <jats:italic><jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content><\/jats:italic> variants were analysed in expression studies for enzymatic activity and processing by immunoblotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six patients had a non\u2010neuronopathic phenotype and 11 a neuronopathic phenotype, three of whom had epilepsy. Total deletion of <jats:italic><jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content><\/jats:italic> invariably resulted in the neuronopathic phenotype. Phenotypes of seven known <jats:italic><jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content><\/jats:italic> variants were consistent with the literature. Expression studies of nine variants were novel and showed impaired <jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content> enzymatic activity, aberrant intracellular processing, and elevated urinary excretion of heparan sulphate and dermatan sulphate irrespective of the <jats:styled-content style=\"fixed-case\">MPS II<\/jats:styled-content> phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>We speculate that very low or cell\u2010type\u2010specific <jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content> residual activity is sufficient to prevent the neuronal phenotype of <jats:styled-content style=\"fixed-case\">MPS II<\/jats:styled-content>. Whereas the molecular effects of <jats:italic><jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content><\/jats:italic> variants do not distinguish between <jats:styled-content style=\"fixed-case\">MPS II<\/jats:styled-content> phenotypes, the <jats:italic><jats:styled-content style=\"fixed-case\">IDS<\/jats:styled-content><\/jats:italic> genotype is a strong predictor.<\/jats:p><\/jats:sec>","DOI":"10.1111\/dmcn.13467","type":"journal-article","created":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T17:18:40Z","timestamp":1495732720000},"page":"1063-1070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Genotype\u2013phenotype relationship in mucopolysaccharidosis <scp>II<\/scp>: predictive power of <i>IDS<\/i> variants for the neuronopathic phenotype"],"prefix":"10.1111","volume":"59","author":[{"given":"Audrey A M","family":"Vollebregt","sequence":"first","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases Erasmus Medical Center Rotterdam The Netherlands"},{"name":"Department of Pediatrics Division of Metabolic Diseases and Genetics Erasmus Medical Center \u2013 Sophia Children's Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Hoogeveen\u2010Westerveld","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases Erasmus Medical Center Rotterdam The Netherlands"},{"name":"Molecular Stem Cell Biology Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian A","family":"Kroos","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases Erasmus Medical Center Rotterdam The Netherlands"},{"name":"Molecular Stem Cell Biology Department of Clinical Genetics Erasmus Medical Center Rotterdam The 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Rotterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ans T","family":"van der Ploeg","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases Erasmus Medical Center Rotterdam The Netherlands"},{"name":"Department of Pediatrics Division of Metabolic Diseases and Genetics Erasmus Medical Center \u2013 Sophia Children's Hospital Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7042-2482","authenticated-orcid":false,"given":"W W M Pim","family":"Pijnappel","sequence":"additional","affiliation":[{"name":"Center for Lysosomal and Metabolic Diseases Erasmus Medical Center Rotterdam The Netherlands"},{"name":"Department of Pediatrics Division of Metabolic Diseases and Genetics Erasmus Medical Center \u2013 Sophia Children's Hospital Rotterdam The Netherlands"},{"name":"Molecular Stem Cell Biology Department of Clinical Genetics Erasmus Medical Center 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