{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T20:49:54Z","timestamp":1760906994729},"reference-count":23,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T00:00:00Z","timestamp":1390435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:sec><jats:label \/><jats:p>Here we report on two unrelated male patients with syndromic intellectual disability (ID) due to duplication at Xq13.3\u2013q21.1, a region of about 6\u2009Mb and 25 genes. Among these, the most outstanding is <jats:italic>ATRX<\/jats:italic>, the causative gene of X\u2010linked alpha\u2010thalassemia\/mental retardation. <jats:italic>ATRX<\/jats:italic> belongs to the growing list of genes implied in chromatin remodeling causing ID. Many these genes, such as <jats:italic>MECP2<\/jats:italic>, are dose\u2010sensitive so that not only deletions and point mutations, but also duplications cause ID. Both patients have severe ID, absent expressive speech, early hypotonia, behavior problems (hyperactivity, repetitive self\u2010stimulatory behavior), postnatal growth deficiency, microcephaly, micrognathia, cryptorchidism, low\u2010set, posteriorly angulated ears, and downslanting palpebral fissures. These findings are also usually present among patients with loss\u2010of\u2010function mutations of the <jats:italic>ATRX<\/jats:italic> gene. Completely skewed X inactivation was observed in the only informative carrier mother, a constant finding among female carriers of inactivating point mutations of this gene. Participation of other duplicated genes cannot be excluded; nevertheless we propose that the increased dosage of <jats:italic>ATRX<\/jats:italic> is the major pathogenic mechanism of this X\u2010linked disorder, a syndrome reminiscent of <jats:italic>MECP2<\/jats:italic> duplication. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.36371","type":"journal-article","created":{"date-parts":[[2014,1,23]],"date-time":"2014-01-23T23:38:29Z","timestamp":1390520309000},"page":"918-923","source":"Crossref","is-referenced-by-count":11,"title":["Duplication at Xq13.3\u2013q21.1 with syndromic intellectual disability, a probable role for the <i>ATRX<\/i> gene"],"prefix":"10.1002","volume":"164","author":[{"given":"Francisco","family":"Mart\u00ednez","sequence":"first","affiliation":[{"name":"Unidad de Gen\u00e9tica y Diagnostico Prenatal Hospital Universitario y Polit\u00e9cnico La Fe Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00f3nica","family":"Rosell\u00f3","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica y Diagnostico Prenatal Hospital Universitario y Polit\u00e9cnico La Fe Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Mayo","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica y Diagnostico Prenatal Hospital Universitario y Polit\u00e9cnico La Fe Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandra","family":"Monfort","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica y Diagnostico Prenatal Hospital Universitario y Polit\u00e9cnico La Fe Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvestre","family":"Oltra","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica y Diagnostico Prenatal Hospital Universitario y Polit\u00e9cnico La Fe Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carmen","family":"Orellana","sequence":"additional","affiliation":[{"name":"Unidad de Gen\u00e9tica y Diagnostico Prenatal Hospital Universitario y Polit\u00e9cnico La Fe Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,1,23]]},"reference":[{"key":"e_1_2_6_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 RC","year":"1992","journal-title":"Am J Hum Genet"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.3.253"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/378818"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.010"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20564"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90287-2"},{"key":"e_1_2_6_9_1","first-page":"73","article-title":"Japanese Mental Retardation Consortium. 2012. 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