{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T14:12:42Z","timestamp":1746195162230,"version":"3.30.2"},"reference-count":14,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The <jats:italic>DYNC2H1<\/jats:italic> gene has been associated with short\u2010rib polydactyly syndrome (SRPS), among other skeletal ciliopathies. Two cases are presented of distinctive phenotypes resulting from splicing variants in <jats:italic>DYNC2H1<\/jats:italic>. The first is a 14\u2010week\u2010old fetus with enlarged nuchal translucency, oral hamartoma, malformed uvula, bifid epiglottis, short ribs, micromelia, long bone agenesis, polysyndactyly, heart defect, pancreatic cysts, multicystic dysplastic kidney, megabladder and trident acetabulum. A ciliopathies NGS panel revealed two compound heterozygous variants in <jats:italic>DYNC2H1<\/jats:italic>: c.7840\u201018T&gt;G r.7841_7964del p.Gly2614Aspfs*5 and c.11070G&gt;A r.11044_11116del p.Ile3682Aspfs*2. Both variants were initially classified as variants of uncertain significance but were reclassified as likely pathogenic after PCR\u2010based RNA testing. The second is an 11\u2010year\u2010old overweight male with multiple accessory oral frenula, median cleft lip and alveolar ridge, polysyndactyly, brachydactyly, normal rib length, and hypogonadism. Exome sequencing revealed two compound heterozygous variants in <jats:italic>DYNC2H1<\/jats:italic>: c.6315del p.(Thr2106Glnfs*7), classified as likely pathogenic, and c.3303\u201016A&gt;G p.(?), classified as a variant of uncertain significance. PCR\u2010based RNA testing suggested that c.3303\u201016A&gt;G induces an in\u2010frame deletion: r.3303_3458del p.Asp1102_Arg1153del, although the normal transcript is still produced. These results are consistent with both SRPS type I\/III in the first case and orofaciodigital syndrome in the second, an unprecedented description. This work thus improves the clinical and molecular knowledge of the phenotypes associated with splicing variants in the <jats:italic>DYNC2H1<\/jats:italic> gene.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ahg.12581","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T13:40:47Z","timestamp":1727962847000},"page":"24-30","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<i>DYNC2H1<\/i> splicing variants causing severe prenatal short\u2010rib polydactyly syndrome and postnatal orofaciodigital syndrome"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9423-956X","authenticated-orcid":false,"given":"Alice","family":"Porto Vasconcelos","sequence":"first","affiliation":[{"name":"Genetics Service S\u00e3o Jo\u00e3o Universitary Hospital Center  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Quental","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)  Porto Portugal"},{"name":"i3S \u2010 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Parente","family":"Freixo","sequence":"additional","affiliation":[{"name":"i3S \u2010 Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade Universidade do Porto  Porto Portugal"},{"name":"CGPP\u2010IBMC Universidade do Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Machado","family":"Pacheco","sequence":"additional","affiliation":[{"name":"Pathology Department S\u00e3o Jo\u00e3o Universitary Hospital Center  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology Department S\u00e3o Jo\u00e3o Universitary Hospital Center  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magda","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynaecology Department S\u00e3o Jo\u00e3o Universitary Hospital Center  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Genetics Service S\u00e3o Jo\u00e3o Universitary Hospital Center  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Costa","family":"Braga","sequence":"additional","affiliation":[{"name":"Pathology Department S\u00e3o Jo\u00e3o Universitary Hospital Center  Porto Portugal"},{"name":"Faculty of Medicine University of Porto  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rita","family":"Quental","sequence":"additional","affiliation":[{"name":"Genetics Service S\u00e3o Jo\u00e3o Universitary Hospital Center  Porto Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a028191"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000019169"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007774"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-021-00925-x"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11604-020-00920-w"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13958"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac958"},{"key":"e_1_2_11_9_1","unstructured":"NCBI. (2004).DYNC2H1 [Internet]. Bethesda (MD): National Library of Medicine (US) National Center for Biotechnology Information (NCBI).https:\/\/www.ncbi.nlm.nih.gov\/gene\/"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-022-01276-7"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2017.60"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.11.016"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.06.017"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-0915-1"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/jop.13339"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.12581","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,17]],"date-time":"2024-12-17T10:22:55Z","timestamp":1734430975000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.12581"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,3]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1]]}},"alternative-id":["10.1111\/ahg.12581"],"URL":"https:\/\/doi.org\/10.1111\/ahg.12581","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"type":"print","value":"0003-4800"},{"type":"electronic","value":"1469-1809"}],"subject":[],"published":{"date-parts":[[2024,10,3]]},"assertion":[{"value":"2024-05-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}