{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:11:30Z","timestamp":1774645890282,"version":"3.50.1"},"reference-count":31,"publisher":"Wiley","issue":"11-12","license":[{"start":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T00:00:00Z","timestamp":1568419200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873482 81873483"],"award-info":[{"award-number":["81873482 81873483"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Genesis"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Acrodysostosis is an extremely rare disorder at birth, that is, characterized by skeletal dysplasia with short stature and midfacial hypoplasia, which has been reported to be caused by <jats:italic>PDE4D<\/jats:italic> and <jats:italic>PRKAR1A<\/jats:italic> gene mutations. Here, a Chinese boy with acrodysostosis, ventricular septal defect, and pulmonary hypertension was recruited for our study, and his clinical and biochemical characteristics were analyzed. A novel de novo heterozygous missense mutation (NM_001104631: c.2030A&gt;C, p.Tyr677Ser) of the <jats:italic>PDE4D<\/jats:italic> gene was detected by whole exome sequencing and confirmed by Sanger sequencing. The c.2030A&gt;C (p.Tyr677Ser) variant was located in exon 15 of the <jats:italic>PDE4D<\/jats:italic> gene, predicted to be damaging by a functional prediction program and shown to be highly conserved among many species. Further functional analysis showed that the p.Tyr677Ser substitution changes the function of the PDE4D protein, affects its subcellular localization in transfected cells, increases PDE4 activity in the regulation of cAMP signaling and affects cell proliferation. Our study identified a novel de novo <jats:italic>PDE4D<\/jats:italic> mutation in acrodysostosis of Chinese origin that not only contributes a deeper appreciation of the phenotypic characteristics of patients with <jats:italic>PDE4D<\/jats:italic> mutations but also expands the spectrum of <jats:italic>PDE4D<\/jats:italic> mutations.<\/jats:p>","DOI":"10.1002\/dvg.23336","type":"journal-article","created":{"date-parts":[[2019,9,14]],"date-time":"2019-09-14T13:04:33Z","timestamp":1568466273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A novel de novo <i>PDE4D<\/i> gene mutation identified in a Chinese patient with acrodysostosis"],"prefix":"10.1002","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4257-7257","authenticated-orcid":false,"given":"Yongkun","family":"Zhan","sequence":"first","affiliation":[{"name":"Cardiovascular Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weicheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyu","family":"Feng","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaozhong","family":"Tan","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Children's Hospital of Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengru","family":"Li","sequence":"additional","affiliation":[{"name":"Cardiovascular Center Children's Hospital of Fudan University  Shanghai 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 Shanghai China"},{"name":"Shanghai Key Laboratory of Birth Defects  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,9,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2214\/ajr.128.1.95"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"issue":"12","key":"e_1_2_6_4_1","first-page":"E1414","article-title":"Engineered stabilization and structural analysis of the autoinhibited conformation of PDE4","volume":"112","author":"Cedervall P.","year":"2015","journal-title":"Proceedings of the National Academy of Sciences of the United States of 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