{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T22:35:01Z","timestamp":1763591701016},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"the key research and development project of Ningxia Hui Autonomous Region","award":["2020BEG03047"],"award-info":[{"award-number":["2020BEG03047"]}]},{"name":"the training project of the scientific innovation commanding talented person in Ningxia Hui Autonomous Region","award":["KJT2020013"],"award-info":[{"award-number":["KJT2020013"]}]},{"name":"the Key Research and Development Project of Ningxia Hui Autonomous Region","award":["2021BEG02045"],"award-info":[{"award-number":["2021BEG02045"]}]},{"name":"Clinical-Basic Joint PI program of Aier of Aier Eye Hospital Group","award":["LCER1-003"],"award-info":[{"award-number":["LCER1-003"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive facial features, broad and often angulated thumbs and halluces, short stature, and moderate-to-severe intellectual disability, classified into two types RSTS1 (<jats:italic>CREBBP<\/jats:italic>-RSTS) and RSTS2 (<jats:italic>EP300<\/jats:italic>-RSTS). More often, the clinical features are inconclusive and the diagnosis of RSTS is established in a proband with identification of a heterozygous pathogenic variant in <jats:italic>CREBBP<\/jats:italic> or <jats:italic>EP300<\/jats:italic> to confirm the diagnosis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In this study, to describe an association between the clinical phenotype and the genotype of a RSTS2 patient who was initially diagnosed with severe early-onset high myopia (eoHM) from a healthy Chinese family, we tested the proband of this family by whole exome sequencing (WES) and further verified among other family members by Sanger sequencing. Real-time quantitative PCR was used to detect differences in the relative mRNA expression of candidate genes available in the proband and family members. Comprehensive ophthalmic tests as well as other systemic examinations were also performed on participants with various genotypes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Whole-exome sequencing revealed that the proband carried the heterozygous frameshift deletion variant c.3714_3715del (p.Leu1239Glyfs*3) in the <jats:italic>EP300<\/jats:italic> gene, which was not carried by the normal parents and young sister as verified by Sanger sequencing, indicating that the variant was <jats:italic>de novo<\/jats:italic>. Real-time quantitative PCR showed that the mRNA expression of <jats:italic>EP300<\/jats:italic> gene was lower in the proband than in other normal family members, indicating that such a variant caused an effect on gene function at the mRNA expression level. The variant was classified as pathogenic as assessed by the interpretation principles of HGMD sequence variants and ACMG guidelines. According to ACMG guidelines, the heterozygous frameshift deletion variant c.3714_3715del (p.Leu1239Glyfs*3) in the <jats:italic>EP300<\/jats:italic> gene was more likely the pathogenic variant of this family with RSTS2.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Therefore, in this paper, we first report <jats:italic>de novo<\/jats:italic> heterozygous variation in <jats:italic>EP300<\/jats:italic> causing eoHM-RSTS. Our study extends the genotypic spectrums for <jats:italic>EP300<\/jats:italic>-RSTS and better assists physicians in predicting, diagnosis, genetic counseling, eugenics guidance and gene therapy for <jats:italic>EP300<\/jats:italic>-RSTS.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12920-023-01516-9","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T09:12:25Z","timestamp":1682068345000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["De novo variation in EP300 gene cause Rubinstein-Taybi syndrome 2 in a Chinese family with severe early-onset high myopia"],"prefix":"10.1186","volume":"16","author":[{"given":"Xiaoyu","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Rui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weining","family":"Rong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xunlun","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"1516_CR1","first-page":"30","volume":"6","author":"CA Stevens","year":"1990","unstructured":"Stevens CA, Carey JC, Blackburn BL. 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Our study, which adhered to the Declaration of Helsinki, was approved and reviewed by the Ethics Committee on Human Research at People Hospital of Ningxia Hui Autonomous Region(reference number:20190909). Before participation, written informed consent was received from each participant or their legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Each participant or their legal guardians give informed consent for the material to appear in BMC Medical Genomics and associated publications without limit on the duration of publication.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"I declare that the authors have no competing interests as defined by Clinical Genetics or other interests that might be perceived to influence the results and discussion reported in this paper.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"84"}}