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The objective of this study was to compare heterozygotes and non\u2010heterozygotes for MPS II, in order to test the hypothesis that heterozygotes may present subtle manifestations of the disease. In this observational and transversal study we collected data on 40 Brazilian women with a positive familial history for MPS II that included clinical and physical exam, karyotype, pattern of X\u2010inactivation, iduronate\u20102\u2010sulfatase (IDS) activity in leukocytes and plasma, urinary glycosaminoglycans levels, computerized tomography scans (CT) of abdomen and spine, and brain magnetic resonance imaging. The Results showed the following: According to DNA analysis, 22 women were classified as heterozygote and 18 as non\u2010heterozygotes. We did not find any abnormality on physical examination, karyotype, or spine CT. Also the pattern of X\u2010inactivation was not different between the groups. Applying the Bonferroni's correction, both groups were found to differ only in relation to IDS activity in plasma and in leukocyte, which were lower in heterozygotes. In our investigation we did not find any evidence of subtle clinical manifestations of MPS II in heterozygotes. Our findings suggest there is no relation between the absence of clinical signs in these women and the occurrence of a favorable skewing pattern of X\u2010inactivation. \u00a9 2010 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.33770","type":"journal-article","created":{"date-parts":[[2010,12,28]],"date-time":"2010-12-28T21:31:48Z","timestamp":1293571908000},"page":"50-57","source":"Crossref","is-referenced-by-count":12,"title":["Are MPS II heterozygotes actually asymptomatic? A study based on clinical and biochemical data, X\u2010inactivation analysis and imaging evaluations"],"prefix":"10.1002","volume":"155","author":[{"given":"Louise Lapagesse","family":"de Camargo Pinto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sharbel Weidner","family":"Maluf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Leistner\u2010Segal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camila","family":"Zimmer da Silva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Brusius\u2010Facchin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maira Graef","family":"Burin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Brustolin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Llerena","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Moraes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonardo","family":"Vedolin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice","family":"Schuch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Giugliani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida Vanessa Doederlein","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2010,12,28]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"1220","article-title":"Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen\u2010receptor gene correlates with X chromosome inactivation","volume":"51","author":"Allen RC","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.105.1.e10"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19990611)84:5<420::AID-AJMG6>3.0.CO;2-Z"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000005658.14563.77"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0112-z"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1989.00520420093029"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/j.1399-0004.1986.tb01896.x","article-title":"Full expression of Hunter's disease in a female with an X\u2010chromosome deletion leading to non\u2010random inactivation","volume":"20","author":"Broadhead DM","year":"1986","journal-title":"Clin Genet"},{"key":"e_1_2_7_9_1","first-page":"289","article-title":"Hunter disease (mucopolysaccharidosis type II) associated with unbalanced inactivation of X chromosomes in a karyotypically normal girl","volume":"49","author":"Clarke JT","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.10.e29"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.036327"},{"key":"e_1_2_7_12_1","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1093\/clinchem\/38.6.803","article-title":"Measuring urinay glycosaminoglicans in the presence of protein: An improved screening procedure for mucopolyssacharidoses based on dimethylmethylene blue","volume":"38","author":"de Jong JG","year":"1992","journal-title":"Clin Chem"},{"key":"e_1_2_7_13_1","first-page":"3773","volume-title":"\u03b1 galactosidase A deficiency: Fabry disease","author":"Desnick RJ","year":"2001"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30123"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.89.1.e2"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5654.418"},{"key":"e_1_2_7_17_1","first-page":"63","volume-title":"Fabry disease perspectives from 5 years of FOS, 1e","author":"Germain DP","year":"2006"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10897-008-9179-7"},{"key":"e_1_2_7_19_1","unstructured":"GiuglianiR.MPS Brazil Network (2009) Personal communication."},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)10028-4"},{"key":"e_1_2_7_21_1","unstructured":"http:\/\/rsb.info.nih.gov\/ij.Imaging and processing analysis in JAVA. 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