{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T21:11:51Z","timestamp":1774645911237,"version":"3.50.1"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T00:00:00Z","timestamp":1618444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004504","name":"Lietuvos Mokslo Taryba","doi-asserted-by":"publisher","award":["S-MIP-17-19\/LSS-150000-1179"],"award-info":[{"award-number":["S-MIP-17-19\/LSS-150000-1179"]}],"id":[{"id":"10.13039\/501100004504","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Endocr Disord"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Acrodysostosis is a rare hereditary disorder described as a primary bone dysplasia with or without hormonal resistance. Pathogenic variants in the <jats:italic>PRKAR1A<\/jats:italic> and <jats:italic>PDE4D<\/jats:italic> genes are known genetic causes of this condition. The latter gene variants are more frequently identified in patients with midfacial and nasal hypoplasia and neurological involvement. The aim of our study was to analyse and confirm a genetic cause of acrodysostosis in a male patient.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We report on a 29-year-old Lithuanian man diagnosed with acrodysostosis type 2. The characteristic phenotype includes specific skeletal abnormalities, facial dysostosis, mild intellectual disability and metabolic syndrome. Using patient\u2019s DNA extracted from peripheral blood sample, the novel, likely pathogenic, heterozygous de novo variant NM_001104631.2:c.581G\u2009&gt;\u2009C was identified in the gene <jats:italic>PDE4D<\/jats:italic> via Sanger sequencing. This variant causes amino acid change (NP_001098101.1:p.(Arg194Pro)) in the functionally relevant upstream conserved region 1 domain of PDE4D.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This report further expands the knowledge of the consequences of missense variants in <jats:italic>PDE4D<\/jats:italic> that affect the upstream conserved region 1 regulatory domain and indicates that pathogenic variants of the gene <jats:italic>PDE4D<\/jats:italic> play an important role in the pathogenesis mechanism of acrodysostosis type 2 without significant hormonal resistance.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12902-021-00741-6","type":"journal-article","created":{"date-parts":[[2021,4,15]],"date-time":"2021-04-15T14:44:14Z","timestamp":1618497854000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A novel variant in the PDE4D gene is the cause of Acrodysostosis type 2 in a Lithuanian patient: a case report"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8669-7192","authenticated-orcid":false,"given":"Gunda","family":"Petraityt\u0117","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kamil\u0117","family":"\u0160iauryt\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Violeta","family":"Mik\u0161tien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loreta","family":"Cimbalistien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dovil\u0117","family":"Kriau\u010di\u016bnien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Au\u0161ra","family":"Matulevi\u010dien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Algirdas","family":"Utkus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Egl\u0117","family":"Preik\u0161aitien\u0117","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,4,15]]},"reference":[{"key":"741_CR1","doi-asserted-by":"publisher","first-page":"P1","DOI":"10.1530\/EJE-16-0107","volume":"175","author":"S Thiele","year":"2016","unstructured":"Thiele S, Mantovani G, Barlier A, Boldrin V, Bordogna P, Sanctis L, et al. From pseudohypoparathyroidism to inactivating PTH\/PTHrP signalling disorder (iPPSD), a novel classification proposed by the EuroPHP network. Eur J Endocrinol. 2016;175:P1\u2013P17.","journal-title":"Eur J Endocrinol"},{"key":"741_CR2","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.ajhg.2012.03.003","volume":"90","author":"C Michot","year":"2012","unstructured":"Michot C, Le Goff C, Goldenberg A, Abhyankar A, Klein C, Kinning E, et al. Exome sequencing identifies PDE4D mutations as another cause of acrodysostosis. Am J Hum Genet. 2012;90:740\u20135.","journal-title":"Am J Hum Genet"},{"key":"741_CR3","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.ajhg.2012.03.004","volume":"90","author":"H Lee","year":"2012","unstructured":"Lee H, Graham JM, Rimoin DL, Lachman RS, Krejci P, Tompson SW, et al. Exome sequencing identifies PDE4D mutations in acrodysostosis. 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The study was approved by the Vilnius Regional Biomedical Research Ethics Committee of Lithuania. Written informed consent for genetic investigations was obtained from the family.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The patient\u2019s parents provided the written consent for the case report to be published. Informed consent from parents regarding photographs for publication has been obtained. The parents signed on behalf of the patient because of his cognitive deficit. A copy of informed consent is available to the journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"71"}}