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Molecular analysis was performed for a total of 355 MPS patients with MPSI (<jats:italic>n<\/jats:italic>\u2009=\u200915), MPSII (<jats:italic>n<\/jats:italic>\u2009=\u2009218), MPSIIIA (<jats:italic>n<\/jats:italic>\u2009=\u200986), MPSIIIB (<jats:italic>n<\/jats:italic>\u2009=\u200920), MPSIVA (<jats:italic>n<\/jats:italic>\u2009=\u20096) or MPSVI (<jats:italic>n<\/jats:italic>\u2009=\u200910). This analysis revealed 104 previously unreported mutations: seven in <jats:italic>IDUA<\/jats:italic> (MPSI), 61 in <jats:italic>IDS<\/jats:italic> (MPSII), 19 in <jats:italic>SGSH<\/jats:italic> (MPSIIIA), 11 in <jats:italic>NAGLU<\/jats:italic> (MPSIIIB), two in <jats:italic>GALNS<\/jats:italic> (MPSIVA) and four in <jats:italic>ARSB<\/jats:italic> (MPSVI). The intergenic comparison of the mutation data for these disorders has revealed interesting differences. Whereas <jats:italic>IDUA<\/jats:italic>, <jats:italic>IDS<\/jats:italic>, <jats:italic>NAGLU<\/jats:italic> and <jats:italic>ARSB<\/jats:italic> demonstrate similar levels of mutation heterogeneity (0.6\u20130.675 different mutations per total alleles), <jats:italic>SGSH<\/jats:italic> and <jats:italic>GALNS<\/jats:italic> have lower levels of mutation heterogeneity (0.282 and 0.455, respectively), due to more recurrent mutations. The type of mutation also varies significantly by gene. <jats:italic>SGSH<\/jats:italic>, <jats:italic>GALNS<\/jats:italic> and <jats:italic>ARSB<\/jats:italic> mutations are usually missense (76.5 %, 81.8 % and 85 %), while <jats:italic>IDUA<\/jats:italic> has many more nonsense mutations (56 %) than the other genes (\u226420%). The mutation spectrum is most diverse for <jats:italic>IDS<\/jats:italic>, including intergenic inversions and multi\u2010exon deletions. By testing 102 mothers of MPSII patients, we determined that 22.5 % of IDS mutations are <jats:italic>de novo<\/jats:italic>. We report the allele frequency of common mutations for each gene in our patient cohort and the exonic distribution of coding sequence alterations in the <jats:italic>IDS<\/jats:italic>, <jats:italic>SGSH<\/jats:italic> and <jats:italic>NAGLU<\/jats:italic> genes, which reveals several potential \u201chot\u2010spots\u201d. This further molecular characterization of these MPS disorders is expected to assist in the diagnosis and counseling of future patients.<\/jats:p>","DOI":"10.1007\/s10545-012-9533-7","type":"journal-article","created":{"date-parts":[[2012,9,13]],"date-time":"2012-09-13T14:11:56Z","timestamp":1347545516000},"page":"179-187","source":"Crossref","is-referenced-by-count":66,"title":["Molecular characterization of 355 mucopolysaccharidosis patients reveals 104 novel mutations"],"prefix":"10.1002","volume":"36","author":[{"given":"Laura M.","family":"Pollard","sequence":"first","affiliation":[{"name":"Biochemical Diagnostic Laboratory Greenwood Genetic Center 106 Gregor Mendel Circle Greenwood SC 29646 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie R.","family":"Jones","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic Laboratory Greenwood Genetic Center Greenwood SC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Biochemical Diagnostic Laboratory Greenwood Genetic Center 106 Gregor Mendel Circle Greenwood SC 29646 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,9,14]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1979.tb00832.x"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.09.003"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0009-8981(59)90119-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390100606"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.115410"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.4.615"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2011.06.001"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/35.7.1472"},{"key":"e_1_2_7_11_1","first-page":"77","volume-title":"Techniques in diagnostic human biochemical genetics: a laboratory manual","author":"Dembure PP","year":"1991"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac102090v"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.2.137"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2007.00213.x"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2011.03.024"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(82)90674-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9343-3"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20534"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01799255"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1202071109"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2009.86"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(02)00200-7"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","unstructured":"MeyerA KossowK GalA et al (2008)The mutation p.Ser298Pro in the sulphamidase gene (SGSH) is associated with a slowly progressive clinical phenotype in mucopolysaccharidosis type IIIA (Sanfilippo A syndrome).Hum Mutat. 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