{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T18:43:29Z","timestamp":1790448209841,"version":"4.1.0"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>Mutations in <jats:italic>MECP2<\/jats:italic> are the main cause of Rett Syndrome. To date, no pathogenic synonymous <jats:italic>MECP2<\/jats:italic> mutation has yet been identified. Here, we investigated a <jats:italic>de novo<\/jats:italic> synonymous variant <jats:italic>c.48C&gt;T<\/jats:italic> (<jats:italic>p.Gly16Gly<\/jats:italic>) identified in a girl presenting with a typical RTT phenotype.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>\n              <jats:italic>In silico<\/jats:italic> analyses to predict the effects of sequence variation on mRNA splicing were employed, followed by sequencing and quantification of lymphocyte mRNAs from the subject for splice variants <jats:italic>MECP2_E1<\/jats:italic> and <jats:italic>MECP2_E2<\/jats:italic>.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Analysis of mRNA confirmed predictions that this synonymous mutation activates a splice-donor site at an early position in exon 1, leading to a deletion (<jats:italic>r.[=, 48_63del]<\/jats:italic>), codon frameshift and premature stop codon (<jats:italic>p.Glu17Lysfs*16<\/jats:italic>) for <jats:italic>MECP2_E1<\/jats:italic>. For <jats:italic>MECP2_E2<\/jats:italic>, the same premature splice site is used, but as this is located in the 5\u2032untranslated region, no effect on the amino acid sequence is predicted. Quantitative analysis that specifically measured this cryptic splice variant also revealed a significant decrease in the quantity of the correct <jats:italic>MECP2_E1<\/jats:italic> transcript, which indicates that this is the etiologically significant mutation in this patient.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These findings suggest that synonymous variants of <jats:italic>MECP2<\/jats:italic> as well as other known disease genes\u2014and <jats:italic>de novo<\/jats:italic> variants in particular\u2014 should be re-evaluated for potential effects on splicing.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1750-1172-8-108","type":"journal-article","created":{"date-parts":[[2013,7,19]],"date-time":"2013-07-19T00:18:31Z","timestamp":1374193111000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["A synonymous change, p.Gly16Gly in MECP2 Exon 1, causes a cryptic splice event in a Rett syndrome patient"],"prefix":"10.1186","volume":"8","author":[{"given":"Taimoor I","family":"Sheikh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirti","family":"Mittal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary J","family":"Willis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John B","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,7,19]]},"reference":[{"issue":"6","key":"608_CR1","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/0092-8674(92)90610-O","volume":"69","author":"JD Lewis","year":"1992","unstructured":"Lewis JD, Meehan RR, Henzel WJ, Maurer-Fogy I, Jeppesen P, Klein F, Bird A: Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. 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