{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T11:00:05Z","timestamp":1791025205513,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2009,6,8]],"date-time":"2009-06-08T00:00:00Z","timestamp":1244419200000},"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":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenic variations of the <jats:italic>ARX<\/jats:italic> (aristaless\u2010related homeobox) gene are associated with marked phenotypic pleiotropy. These phenotypes are X\u2010linked neurological disorders that include brain and genital malformation and non\u2010malformation syndromes. Typically, malformation phenotypes result from pathogenic variations that are predicted to truncate the ARX protein, or alter residues in the highly conserved homeodomain. While non\u2010malformation phenotypes tend to be caused by pathogenic variations that are predicted to expand the first two polyalanine tracts of ARX, or alter residues outside of the homeodomain. The most common pathogenic variation of the <jats:italic>ARX<\/jats:italic> gene is a duplication of 24 bp, c.429_452 dup, which leads to an expansion of the second polyalanine tract of the ARX protein from 12 to 20 alanine residues. This pathogenic variation is associated with both sporadic and familial nonsyndromic mental retardation. Syndromic manifestations include mental retardation with hand dystonia (Partington syndrome), infantile spasms (West syndrome) and\/or other epileptic seizures. Here, we report on a novel pathogenic variant of a tandem 33 bp duplication that is predicted to result in an expansion of polyalanine tract 2 in two brothers with mental retardation, epilepsy, dystonia, and the novel feature of intermittent hyperventilation. This pathogenic variation is predicted to result in a \u201cnon\u2010homogeneous\u201d polyalanine tract expansion that is longer than predicted expansion caused by the common 24 bp duplication. The location of the novel 33 bp duplication in the same region as the common 24 bp duplication supports this region as the <jats:italic>ARX<\/jats:italic> variation \u201chot spot.\u201d \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32851","type":"journal-article","created":{"date-parts":[[2009,6,8]],"date-time":"2009-06-08T21:10:10Z","timestamp":1244495410000},"page":"1482-1486","source":"Crossref","is-referenced-by-count":18,"title":["Clinical study of two brothers with a novel 33 bp duplication in the <i>ARX<\/i> gene"],"prefix":"10.1002","volume":"149A","author":[{"given":"Michelle K.","family":"Demos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tod","family":"Fullston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"Partington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jozef","family":"G\u00e9cz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William T.","family":"Gibson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,6,8]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2005.04.003"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh277"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.8.981"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0298-164"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10630"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2006.04.003"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.14.7458"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201222"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000266594.16202.c1"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10310"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1086\/518903"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1009"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2003.015412"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320300127"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2007.03.005"},{"key":"e_1_2_6_17_1","first-page":"374","article-title":"X linked mental retardation and infantile spasms in a family: A new clinical data and linkage to Xp11.4\u2010Xp22.11","volume":"36","author":"Str\u00f8mme P","year":"1999","journal-title":"J Med Genet"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng862"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(02)00079-7"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000247833.29314.5b"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.10714"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2004.00256.x"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.32851","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.32851","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T19:46:10Z","timestamp":1697053570000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.32851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,8]]},"references-count":21,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["10.1002\/ajmg.a.32851"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.32851","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6,8]]}}}