{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T16:00:20Z","timestamp":1791043220721,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T00:00:00Z","timestamp":1239580800000},"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":[[2009,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X\u2010linked <jats:italic>MECP2<\/jats:italic> gene. Recently, a new MeCP2 isoform was described, MeCP2_e1, which skips exon 2 and has an alternative N\u2010terminus, translated from exon 1, whereas MeCP2_e2 is translated from a start codon in exon 2. Since the incorporation of exon 1 into standard sequencing protocols for RTT, few exon 1 mutations have been described and are thus assumed to be only rare causes of RTT. Also, studies have suggested that the frameshift mutations identified in exon 1 affect both isoforms. Our aim in this study was to assess the frequency of mutations in exon 1, their relationship to phenotype, and the implications on the etiological role for the isoform MeCP2_e1 in RTT, versus the previously described isoform, MeCP2_e2. We sequenced <jats:italic>MECP2<\/jats:italic> in 51 females with various clinical presentations, including developmental delay, autism, atypical and classical RTT, referred to our laboratories for testing. In patients with identified mutations, X\u2010chromosome inactivation was analyzed. We identified four patients with exon 1 mutations; three were novel (c.1A\u2009&gt;\u2009T; c.1A\u2009&gt;\u2009G; c.5C\u2009&gt;\u2009T), two of which affected the start codon, one a missense change, and one patient had a previously reported splice site mutation, c.62\u2009+\u20091delGT. The four patients fit criteria for classical RTT, and thus these findings add support to previous reports that exon 1 mutations may be associated with a severe phenotype. Also, these findings add significant weight to the mounting evidence suggesting that the MeCP2_e1 isoform is the etiologically relevant form of the protein. \u00a9 2009 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.a.32776","type":"journal-article","created":{"date-parts":[[2009,4,13]],"date-time":"2009-04-13T18:19:01Z","timestamp":1239646741000},"page":"1019-1023","source":"Crossref","is-referenced-by-count":47,"title":["Novel exon 1 mutations in <i>MECP2<\/i> implicate isoform MeCP2_e1 in classical Rett syndrome"],"prefix":"10.1002","volume":"149A","author":[{"given":"Carol J.","family":"Saunders","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berge E.","family":"Minassian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva W.C.","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,4,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.026161"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00604.x"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00712.x"},{"key":"e_1_2_6_6_1","first-page":"101","article-title":"Survival in a large cohort of US girls and women with Rett syndrome","volume":"8","author":"del Junco D","year":"1993","journal-title":"J Child Neurol"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201270"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0317167100004200"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30425"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh349"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.19.5444"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2005.10.037"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90610-O"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1327"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/341123"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2005.11.002"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2005.00444.x"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.036244"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32002"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10242"}],"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.32776","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.32776","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T03:35:22Z","timestamp":1697600122000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.32776"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4,23]]},"references-count":19,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2009,5]]}},"alternative-id":["10.1002\/ajmg.a.32776"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.32776","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4,23]]}}}