{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T00:42:03Z","timestamp":1793752923222,"version":"4.6.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2007,9,17]],"date-time":"2007-09-17T00:00:00Z","timestamp":1189987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Mucopolysaccharidosis IVA is an autosomal recessive disease caused by the deficiency of <jats:italic>N<\/jats:italic>\u2010acetylgalactosamine\u20106\u2010sulfate sulfatase (GALNS). Mutation screening of the <jats:italic>GALNS<\/jats:italic> gene was performed for seven MPS IVA patients with attenuated phenotypes from three unrelated families. Four of 5 missense mutations identified in this study (p.F167V, p.R253W, p.R380S, p.P484S) and two reported (p.F97V, p.N204K), associated with attenuated phenotypes, were characterized using <jats:italic>in vitro<\/jats:italic> stable expression experiments, enzyme kinetic study, protein processing and structural analysis. The stably expressed mutant enzymes defining the attenuated phenotype exhibited a considerable residual activity (1.2\u201336.7% of the wild\u2010type GALNS activity) except for p.R380S. Enzyme kinetic studies showed that p.F97V, p.F167V and p.N204K have lower affinity to the substrate compared with other mutants. The p.F97V enzyme was the most thermolabile at 55\u00b0C. Immunoblot analyses indicated a rapid degradation and\/or an insufficiency in processing in the mutant proteins. Tertiary structure analysis revealed that although there was a tendency for \u2018attenuated\u2019 mutant residues to be located on the surface of GALNS, they have a different effect on the protein including modification of the hydrophobic core and salt\u2010bridge formation and different potential energy. This study demonstrates that \u2018attenuated\u2019 mutant enzymes are heterogeneous in molecular phenotypes, including biochemical properties and tertiary structure.<\/jats:p>","DOI":"10.1007\/s10545-007-0702-z","type":"journal-article","created":{"date-parts":[[2007,9,17]],"date-time":"2007-09-17T10:12:39Z","timestamp":1190023959000},"page":"758-767","source":"Crossref","is-referenced-by-count":34,"title":["Effect of \u2018attenuated\u2019 mutations in mucopolysaccharidosis IVA on molecular phenotypes of <i>N<\/i>\u2010acetylgalactosamine\u20106\u2010sulfate sulfatase"],"prefix":"10.1002","volume":"30","author":[{"given":"A. M.","family":"Monta\u00f1o","sequence":"first","affiliation":[{"name":"Department of Pediatrics Saint Louis University, Pediatric Research Institute 3662 Park Ave. St. Louis MO 63110\u20102586 USA"},{"name":"Department of Pediatrics Gifu University Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Sukegawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Carrozzo","sequence":"additional","affiliation":[{"name":"Servizio di Genetica Medica Istituto Scientifico Ospedale \u2018San Raffaele\u2019 Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Di Natale","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Biotechnologies University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Christensen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, The Juliane Marie Center Copenhagen University Hospital Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. O.","family":"Orii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Orii","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Kondo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gifu University Gifu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Tomatsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Saint Louis University, Pediatric Research Institute 3662 Park Ave. St. Louis MO 63110\u20102586 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,9,17]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"96","article-title":"The morquio A syndrome (mucopolysaccharidosis IVA) gene maps to 16q24.3","volume":"52","author":"Baker E","year":"1993","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1986.tb01262.x"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(97)00185-8"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1997)10:3<223::AID-HUMU8>3.0.CO;2-J"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960628)63:4<558::AID-AJMG9>3.0.CO;2-K"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(03)01069-3"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115919"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1996)8:2<187::AID-HUMU14>3.0.CO;2-Z"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02766953"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.185.4154.862"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050594"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)52451-6"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi9714924"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a123697"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1266"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-003-0959-8"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0529-7"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1994.1132"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1988.tb03422.x"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1988.tb03423.x"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1988.tb03421.x"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(91)90434-D"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.3.341"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02179150"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.9.1283"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0440-7"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)91244-7"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.4.741"},{"key":"e_1_2_1_30_1","first-page":"556","article-title":"Mucopolysaccharidosis IVA: identification of a common missense mutation I113F in the N\u2010acetylgalactosamine\u20106\u2010sulfate sulfatase gene","volume":"57","author":"Tomatsu S","year":"1995","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_31_1","first-page":"950","article-title":"Mucopolysaccharidosis IVA: four new exonic mutations in patients with N\u2010acetylgalactosamine\u20106\u2010sulfate sulfatase deficiency","volume":"58","author":"Tomatsu S","year":"1996","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1997)10:5<368::AID-HUMU6>3.0.CO;2-B"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-004-0178-8"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.9265"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.018010"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20257"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.05.012"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-1004(1998)11:3<202::AID-HUMU4>3.0.CO;2-J"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-007-0702-z","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T05:01:06Z","timestamp":1694754066000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-007-0702-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,9,17]]},"references-count":37,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2007,10]]}},"alternative-id":["10.1007\/s10545-007-0702-z"],"URL":"https:\/\/doi.org\/10.1007\/s10545-007-0702-z","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,9,17]]}}}