{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:54:43Z","timestamp":1791287683936,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T00:00:00Z","timestamp":1361404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2013,12]]},"abstract":"<jats:p>Acrodysostosis is characterized by a peripheral dysostosis that is accompanied by short stature, midface hypoplasia, and developmental delay. Recently, it was shown that heterozygous point mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">PRKAR1A<\/jats:styled-content><\/jats:italic> gene cause acrodysostosis with hormone resistance. By mutational analysis of the <jats:italic><jats:styled-content style=\"fixed-case\">PRKAR1A<\/jats:styled-content><\/jats:italic> gene we detected four different mutations (p.<jats:styled-content style=\"fixed-case\">Arg368Stop<\/jats:styled-content>, p.<jats:styled-content style=\"fixed-case\">Ala213Thr<\/jats:styled-content>, p.<jats:styled-content style=\"fixed-case\">Tyr373Cys<\/jats:styled-content>, and p.<jats:styled-content style=\"fixed-case\">Arg335Cys<\/jats:styled-content>) in four of seven affected patients with acrodysostosis. The combination of clinical results, endocrinological parameters and <jats:italic>in silico<\/jats:italic> mutation analysis gives evidence to suppose a pathogenic effect of each mutation. This assumption is supported by the <jats:italic>de novo<\/jats:italic> origin of these mutations. Apart from typical radiological abnormalities of the hand bones, elevated thyroid stimulating hormone and parathyroid hormone values as well as short stature are the most common findings. Less frequent features are characteristic facial dysmorphisms, sensorineural hearing loss and mild intellectual disability. These results lead to the conclusion that mutations of <jats:italic><jats:styled-content style=\"fixed-case\">PKRAR1A<\/jats:styled-content><\/jats:italic> are the major molecular cause for acrodysostosis with endocrinological abnormalities. In addition, in our cohort of 44 patients affected with brachydactyly type E (<jats:styled-content style=\"fixed-case\">BDE<\/jats:styled-content>) we detected only one sequence variant of <jats:italic><jats:styled-content style=\"fixed-case\">PRKAR1A<\/jats:styled-content><\/jats:italic> (p.<jats:styled-content style=\"fixed-case\">Asp227Asn<\/jats:styled-content>) with an unclear effect on protein function. Thus, we conclude that <jats:italic><jats:styled-content style=\"fixed-case\">PRKAR1A<\/jats:styled-content><\/jats:italic> mutations may play no major role in the pathogenesis of <jats:styled-content style=\"fixed-case\">BDE<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cge.12106","type":"journal-article","created":{"date-parts":[[2013,2,21]],"date-time":"2013-02-21T08:09:40Z","timestamp":1361434180000},"page":"531-538","source":"Crossref","is-referenced-by-count":33,"title":["Novel mutations of the <i><scp>PRKAR1A<\/scp><\/i> gene in\u00a0patients with acrodysostosis"],"prefix":"10.1111","volume":"84","author":[{"given":"F","family":"Muhn","sequence":"first","affiliation":[{"name":"Institute for Medical and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Klopocki","sequence":"additional","affiliation":[{"name":"Institute for Medical and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Max\u2010Planck\u2010Institute for Molecular Genetics  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Graul\u2010Neumann","sequence":"additional","affiliation":[{"name":"Institute for Medical and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Uhrig","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Medical University  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Colley","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, South Western Sydney LHD Liverpool Hospital  Liverpool Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Castori","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, San Camillo\u2010Forlanini Hospital Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E","family":"Lankes","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Otto Heubner Center for Pediatrics, Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Henn","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Saarland University  Homburg Saar Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U","family":"Gruber\u2010Sedlmayr","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Medical University Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W","family":"Seifert","sequence":"additional","affiliation":[{"name":"Institute for Vegetative Anatomy, Charit\u00e9 University Medicine of Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Horn","sequence":"additional","affiliation":[{"name":"Institute for Medical and Human Genetics Charit\u00e9 Universit\u00e4tsmedizin Berlin  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,2,21]]},"reference":[{"key":"e_1_2_6_2_1","first-page":"2189","article-title":"L'acrodysostose","volume":"76","author":"Maroteaux P","year":"1968","journal-title":"Presse Med"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320300416"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002470000355"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320380111"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-199210000-00002"},{"key":"e_1_2_6_7_1","first-page":"822","article-title":"Acrodysostosis: autosomal dominant 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