{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T22:48:39Z","timestamp":1771541319493,"version":"3.50.1"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T00:00:00Z","timestamp":1514419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100007959","name":"Chulabhorn Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007959","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Mucopolysaccharidosis type I (MPS I) is a rare autosomal\u2010recessive disorder caused by defects in alpha\u2010L\u2010iduronidase (IDUA), a lysosomal enzyme encoded by the <jats:italic>IDUA<\/jats:italic> gene. Herein, we characterized <jats:italic>IDUA<\/jats:italic> mutations underlying mucopolysaccharidosis type I intermediate form (Hurler\u2013Scheie syndrome) and its molecular pathogenic mechanisms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Clinical data, activity of the IDUA enzyme in leukocytes, and a mutation of the <jats:italic>IDUA<\/jats:italic> gene were analyzed. Pathogenesis associated with an <jats:italic>IDUA<\/jats:italic> mutation was further investigated by evaluating the mutant cDNA sequence, protein expression and activity in COS\u20107 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Five unrelated patients were identified to have clinical diagnosis of intermediate form of MPS I (Hurler\u2013Scheie) and exhibited low\u2010to\u2010absent levels of leukocyte IDUA activity. Genetic analysis revealed homozygous c.*1T&gt;C (p.X654R) mutation in two patients and compound heterozygosity between the c.*1T&gt;C and another allele including c.265G&gt;A (p.R89Q), c.935G&gt;A (p.W312X), or c.1138 C&gt;T (p.Q380X), each in a single patient. Sequencing the 3\u2032RACE product of the c.*1T&gt;C (p.X654R) allele indicated a 38\u2010amino acids elongation of the mutant protein. COS\u20107 cells expressing IDUA with the mutations exhibited extremely low levels or complete absence of enzyme activity compared to wild\u2010type IDUA. Western blot analysis detected no protein in p.W312X and p.Q380X samples, while an elevated molecular mass and a different pattern of protein bands were found in p.X654R specimen compared with the wild type IDUA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Mutational spectrum underlying intermediate MPS I is expanded. Our data suggest that the p.X654R is an intermediate <jats:italic>IDUA<\/jats:italic> mutant allele with residual enzyme activity. It can lead to intermediate or milder form of MPS I depending on another associated allele.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12236","type":"journal-article","created":{"date-parts":[[2017,12,28]],"date-time":"2017-12-28T05:48:52Z","timestamp":1514440132000},"page":"150-157","source":"Crossref","is-referenced-by-count":5,"title":["<i>p.X654R IDUA<\/i> variant among Thai individuals with intermediate mucopolysaccharidosis type I and its residual activity as demonstrated in COS\u20107 cells"],"prefix":"10.1111","volume":"82","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8960-5692","authenticated-orcid":false,"given":"Lukana","family":"Ngiwsara","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry Chulabhorn Research Institute  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Ketudat\u2010Cairns","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry Chulabhorn Research Institute  Bangkok Thailand"},{"name":"School of Chemistry Institute of Science Suranaree University of Technology  Nakhon Ratchasima Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phannee","family":"Sawangareetrakul","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry Chulabhorn Research Institute  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratana","family":"Charoenwattanasatien","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry Chulabhorn Research Institute  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Voraratt","family":"Champattanachai","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry Chulabhorn Research Institute  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chulaluck","family":"Kuptanon","sequence":"additional","affiliation":[{"name":"Queen Sirikit National Institute of Child Health  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suthipong","family":"Pangkanon","sequence":"additional","affiliation":[{"name":"Queen Sirikit National Institute of Child Health  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thipwimol","family":"Tim\u2010Aroon","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duangrurdee","family":"Wattanasirichaigoon","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Department of Pediatrics Faculty of Medicine Ramathibodi Hospital Mahidol University  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2217-4517","authenticated-orcid":false,"given":"Jisnuson","family":"Svasti","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry Chulabhorn Research Institute  Bangkok Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,12,28]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0929-693X(00)80126-8"},{"key":"e_1_2_8_3_1","first-page":"330","article-title":"Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: Multiple allelic mutations of the IDUA gene in a small geographic area","volume":"53","author":"Bach G.","year":"1993","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21479"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1357"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00711309"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.6.861"},{"key":"e_1_2_8_8_1","unstructured":"Clarke L. 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