{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T09:56:58Z","timestamp":1753869418494,"version":"3.41.2"},"reference-count":21,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,8,19]],"date-time":"2020-08-19T00:00:00Z","timestamp":1597795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"publisher","award":["97\u201001\u201001\u201018124"],"award-info":[{"award-number":["97\u201001\u201001\u201018124"]}],"id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rett syndrome is an X\u2010linked dominant neurodevelopmental disease caused by mutation in the methyl\u2010CpG\u2010binding protein 2 (<jats:italic>MECP2<\/jats:italic>) gene. This gene encodes a methylated DNA\u2010binding protein, which acts as a transcriptional regulatory factor. The present study aimed to establish a cell model of Rett syndrome with the <jats:italic>MECP2<\/jats:italic> synonymous mutation c.354G&gt;T (p.Gly118Gly). In addition, the molecular mechanism of pathogenesis of this mutation was also investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To create a cell line containing the synonymous variant in <jats:italic>MECP2<\/jats:italic> locus, the clustered regularly interspaced short palindromic repeats (CRISPR)\/Cas9\u2010mediated homology\u2010directed repair precise gene editing method was used. In addition, employing the synthesis of cDNA, the effect of this variant on splicing was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using this model and molecular analysis, we found that the c.354G&gt;T synonymous variant created a novel 5' cryptic splice donor site within the exon 3 of <jats:italic>MECP2<\/jats:italic> gene, which resulted in the deletion of 25 nucleotides at the 3' end of exon 3 and presumably protein truncation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The results of the present study show that an apparently neutral synonymous polymorphism, which may be commonly classified as non\u2010pathogenic, may indeed lead to the creation of an aberrant splice site, thereby resulting in disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3258","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T00:04:26Z","timestamp":1596758666000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CRISPR\/Cas9 knock\u2010in toward creating a Rett syndrome cell model with a synonymous mutation in the <i>MECP2<\/i> gene"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7317-906X","authenticated-orcid":false,"given":"Shayan","family":"Khalili Alashti","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jafar","family":"Fallahi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies Shiraz University of Medical Sciences  Shiraz 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