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We investigated X\u2010chromosomal inactivation patterns (XCI) as a potential determinant of symptom severity in FD women.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>We included 95 women with mutations in <jats:italic>GLA<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u200918 with variants of unknown pathogenicity) and 50 related men, and collected mouth epithelial cells, venous blood, and skin fibroblasts for XCI analysis using the methylation status of the androgen receptor gene. The mutated X\u2010chromosome was identified by comparison of samples from relatives. Patients underwent genotype categorization and deep clinical phenotyping of symptom severity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>43\/95 (45%) women carried mutations categorized as classic. The XCI pattern was skewed (i.e., \u226575:25% distribution) in 6\/87 (7%) mouth epithelial cell samples, 31\/88 (35%) blood samples, and 9\/27 (33%) skin fibroblast samples. Clinical phenotype, \u03b1\u2010galactosidase A (GAL) activity, and lyso\u2010Gb3 levels did not show intergroup differences when stratified for X\u2010chromosomal skewing and activity status of the mutated X\u2010chromosome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>X\u2010inactivation patterns alone do not reliably reflect the clinical phenotype of women with FD when investigated in biomaterial not directly affected by FD. However, while XCI patterns may vary between tissues, blood frequently shows skewing of XCI patterns.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2029","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T09:12:00Z","timestamp":1660641120000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["X\u2010chromosomal inactivation patterns in women with Fabry\u00a0disease"],"prefix":"10.1002","volume":"10","author":[{"given":"Laura","family":"Wagenh\u00e4user","sequence":"first","affiliation":[{"name":"Department of Neurology University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Rickert","sequence":"additional","affiliation":[{"name":"Department of Neurology University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[{"name":"Department of Neurology University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Fabry Centre for Interdisciplinary Therapy W\u00fcrzburg (FAZIT) University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Fabry Centre for Interdisciplinary Therapy W\u00fcrzburg (FAZIT) University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Department of Internal Medicine, Division of Nephrology University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2560-4068","authenticated-orcid":false,"given":"Peter","family":"Nordbeck","sequence":"additional","affiliation":[{"name":"Fabry Centre for Interdisciplinary Therapy W\u00fcrzburg (FAZIT) University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Department of Internal Medicine, Division of Cardiology University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Rost","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6973-6428","authenticated-orcid":false,"given":"Nurcan","family":"\u00dc\u00e7eyler","sequence":"additional","affiliation":[{"name":"Department of Neurology University of W\u00fcrzburg  W\u00fcrzburg Germany"},{"name":"Fabry Centre for Interdisciplinary Therapy W\u00fcrzburg (FAZIT) University of W\u00fcrzburg  W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,16]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"1229","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 R. 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