{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T14:21:06Z","timestamp":1760710866930,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BD\/136398\/2018","UIDB\/00215\/2020 and UIDP\/00215\/2020","LA\/P\/0064\/2020","UIDP\/50017\/2020+UIDB\/50017\/2020"],"award-info":[{"award-number":["SFRH\/BD\/136398\/2018","UIDB\/00215\/2020 and UIDP\/00215\/2020","LA\/P\/0064\/2020","UIDP\/50017\/2020+UIDB\/50017\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Departamento de Ensino, Forma\u00e7\u00e3o e Investiga\u00e7\u00e3o","award":["2015-DEFI\/145\/12"],"award-info":[{"award-number":["2015-DEFI\/145\/12"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>X-chromosome inactivation (XCI) is a developmental process to compensate the imbalance in the dosage of X-chromosomal genes in females. A skewing of the XCI pattern may suggest a carrier status for an X-linked disease or explain the presence of a severe phenotype. In these cases, it is important to determine the XCI pattern, conventionally using the gold standard Human Androgen-Receptor Assay (HUMARA), based on the analysis of the methylation status at a polymorphic CAG region in the first exon of the human androgen receptor gene (AR). The aim of this study was to evaluate whether the methylation status of the fragile mental retardation protein translational regulator gene (FMR1) can provide an XCI pattern similar to that obtained by HUMARA. A set of 48 female carriers of FMR1 gene normal-sized alleles was examined using two assays: HUMARA and a FMR1 methylation PCR (mPCR). Ranges were defined to establish the XCI pattern using the methylation pattern of the FMR1 gene by mPCR. Overall, a 77% concordance of the XCI patterns was obtained between the two assays, which led us to propose a set of key points and a stepwise analysis towards obtaining an accurate result for the XCI pattern and to minimize the underlying pitfalls.<\/jats:p>","DOI":"10.3390\/genes13030419","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T10:00:40Z","timestamp":1645783240000},"page":"419","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Use of the FMR1 Gene Methylation Status to Assess the X-Chromosome Inactivation Pattern: A Stepwise Analysis"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-962X","authenticated-orcid":false,"given":"B\u00e1rbara","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Molecular Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3917-2323","authenticated-orcid":false,"given":"Ana","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]},{"given":"Vanessa","family":"Sousa","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3274-2474","authenticated-orcid":false,"given":"Nuno","family":"Maia","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3561-1288","authenticated-orcid":false,"given":"Isabel","family":"Marques","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]},{"given":"Em\u00eddio","family":"Vale-Fernandes","sequence":"additional","affiliation":[{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"},{"name":"Centre for Medically Assisted Procreation\/Public Gamete Bank, Centro Materno-Infantil do Norte Dr. Albino Aroso (CMIN), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4050-651 Porto, Portugal"}]},{"given":"Ros\u00e1rio","family":"Santos","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7089-2508","authenticated-orcid":false,"given":"Ant\u00f3nio J. A.","family":"Nogueira","sequence":"additional","affiliation":[{"name":"CESAM\u2014Center for Environmental and Marine Studies, Department of Biology, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Paula","family":"Jorge","sequence":"additional","affiliation":[{"name":"Molecular Genetics Unit, Centro de Gen\u00e9tica M\u00e9dica Dr. Jacinto Magalh\u00e3es (CGM), Centro Hospitalar Universit\u00e1rio do Porto (CHUPorto), 4099-028 Porto, Portugal"},{"name":"UMIB\u2014Unit for Multidisciplinary Research in Biomedicine, ICBAS\u2014School of Medicine and Biomedical Sciences, University of Porto, 4050-313 Porto, Portugal"},{"name":"ITR\u2014Laboratory for Integrative and Translational Research in Population Health, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1038\/s41436-020-0779-4","article-title":"X-linked diseases: Susceptible females","volume":"22","author":"Migeon","year":"2020","journal-title":"Genet. 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