{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:24:29Z","timestamp":1778635469986,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81741036"],"award-info":[{"award-number":["81741036"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Rubinstein\u2013Taybi syndrome (RSTS) is a rare genetic disease characterized by broad thumbs and halluces, facial dysmorphisms, short stature, and intellectual disability. RSTS is mainly caused by de novo variants in epigenetics\u2010associated gene, <jats:italic>CREBBP<\/jats:italic>. To date, there is no cohort study of <jats:italic>CREBBP<\/jats:italic> variants in Chinese RSTS patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, 18 kids who meet the main criteria of RSTS were recruited. Molecular diagnoses were analyzed by clinical exome sequencing (CES), and the medical records were reviewed retrospectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Nineteen novel <jats:italic>CREBBP<\/jats:italic> variants in 18 RSTS patients were identified, including two missense, four nonsense, five frameshift, one splicing variants, and seven intragenic deletions. A higher incidence (37%,\u00a07\/19) of intragenic deletions was detected. One patient who had two de novo missense variants c.[4112T\u00a0&gt;\u00a0A, 4118C\u00a0&gt;\u00a0A] in cis and one patient who had a de novo frameshift variant c.5837delC in homozygous state (90%) were found in this study. Compared with the previously reported populations, seven clinical features were different, including the higher incidence of polydactyly, syndactyly, microcephaly, and micrognathia, and the lower incidence of angulated thumbs, autistic behavior, and epilepsy. One patient with obesity in the first year was diagnosed with <jats:italic>CREBBP<\/jats:italic> gene exon 2 deletion, was initially suspected of Prader\u2013Willi syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>We reported the genetic and clinical information of 18 RSTS patients from Chinese population with novel <jats:italic>CREBBP<\/jats:italic> variants. This study provides a new insight into RSTS and illustrates the value of applying CES which increases the diagnostic yields and enhances the clinical care of RSTS patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1009","type":"journal-article","created":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T08:08:56Z","timestamp":1571731736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Clinical exome sequencing identifies novel <i>CREBBP<\/i> variants in 18 Chinese Rubinstein\u2013Taybi Syndrome kids with high frequency of polydactyly"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8487-974X","authenticated-orcid":false,"given":"Sha","family":"Yu","sequence":"first","affiliation":[{"name":"Key Laboratory of Birth Defects Pediatrics Research Institute Children\u2019s Hospital of Fudan University Shanghai 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