{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:41:19Z","timestamp":1772253679840,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,1,4]],"date-time":"2022-01-04T00:00:00Z","timestamp":1641254400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["19ek0109301"],"award-info":[{"award-number":["19ek0109301"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Rubinstein\u2010Taybi syndrome (RSTS) is characterized by dysmorphic facial features, broad thumbs, and intellectual disability. CREB\u2010binding protein (\n                    <jats:italic>CREBBP<\/jats:italic>\n                    ) or E1A\u2010binding protein P300 (\n                    <jats:italic>EP300<\/jats:italic>\n                    ) are causative genes. To elucidate the underlying genetic and genomic architecture related to the RSTS phenotype, we performed comprehensive genetic analysis targeting\n                    <jats:italic>CREBBP<\/jats:italic>\n                    and\/or\n                    <jats:italic>EP300<\/jats:italic>\n                    in 22 clinically diagnosed patients. During the 11\u2010year study period, we used several analysis methods including high\u2010resolution melting, array\u2010based comparative genomic hybridization, panel\u2010based exome sequencing, whole exome sequencing, and whole genome sequencing (WGS). We identified the causative variants in 19 patients (86.3%), but they were variable and complex, so we must combine multiple analysis methods. Notably, we found genetic alterations in the non\u2010coding regions of two patients (10.5%, 2\/19): scattered deletions including a partial 5\u2032\u2010untranslated region of\n                    <jats:italic>CREBBP<\/jats:italic>\n                    in one patient (all coding exons were intact), and a deep 229\u2010bp intronic deletion in another patient, resulting in a splicing error. Furthermore, we identified rare clinical findings: two patients with an\n                    <jats:italic>EP300<\/jats:italic>\n                    variant showed abnormal development of the neural tube, and one patient with a\n                    <jats:italic>CREBBP<\/jats:italic>\n                    variant had anorectal atresia with a cloaca. Our findings expand the allelic heterogeneity of RSTS, underscore the utility of comprehensive genetic analysis, and suggest that WGS may be a practical diagnostic strategy.\n                  <\/jats:p>","DOI":"10.1111\/cge.14103","type":"journal-article","created":{"date-parts":[[2021,12,27]],"date-time":"2021-12-27T06:24:54Z","timestamp":1640586294000},"page":"335-345","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Divergent variant patterns among 19 patients with\n                    <scp>Rubinstein\u2010Taybi<\/scp>\n                    syndrome uncovered by comprehensive genetic analysis including whole genome sequencing"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2704-9010","authenticated-orcid":false,"given":"Yumi","family":"Enomoto","sequence":"first","affiliation":[{"name":"Clinical Research Institute Kanagawa Children's Medical Center Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Yokoi","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshinori","family":"Tsurusaki","sequence":"additional","affiliation":[{"name":"Clinical Research Institute Kanagawa Children's Medical Center Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makiko","family":"Tominaga","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics Kanagawa Children's Medical Center Yokohama 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