{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:26:20Z","timestamp":1767626780145,"version":"3.37.3"},"reference-count":22,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,4,21]],"date-time":"2018-04-21T00:00:00Z","timestamp":1524268800000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>Spondylocostal dysostosis (SCD) is a rare disorder characterized by vertebral segmentation defects and malformations of the ribs. SCD patients have some degree of (kypho)scoliosis, short stature and suffer from respiratory impairment due to the reduced size of their thoracic cage. Mutations in <jats:italic>DLL3<\/jats:italic>, <jats:italic>MESP2<\/jats:italic>, <jats:italic>LFNG<\/jats:italic>, <jats:italic>HES7<\/jats:italic>, <jats:italic>TBX6<\/jats:italic>, and <jats:italic>RIPPLY2<\/jats:italic> are known to cause different subtypes of SCD. Here, we report on a male neonate with an apparent distinct SCD\u2010like phenotype only partly overlapping the previously described SCD subtypes. The proband presented with severe rib malformations (missing, fused, bifid, and hypoplastic ribs), vertebral malformations (intervertebral fusions of the laminae and irregular ossification of the vertebral bodies), and a mild scoliosis. Clear segmentation defects of the vertebral bodies were lacking. Other dysmorphic features were present as well. Severe respiratory insufficiency was present from birth. Whole exome sequencing identified a homozygous start\u2010loss variant in <jats:italic>DMRT2<\/jats:italic> (NM_006557.6: c.1A\u2009&gt;\u2009T p.[Met1?]) being a likely cause of the SCD\u2010like phenotype in the proband. Mutations in <jats:italic>DMRT2<\/jats:italic> (OMIM#604935) have not been described in relation to SCD\u2010related phenotypes in humans before. However, <jats:italic>Dmrt2<\/jats:italic> knock\u2010out mice exhibit severe rib and vertebral defects that strikingly overlap with the radiological phenotype of the proband reported here. Therefore, it seems plausible that mutations in <jats:italic>DMRT2<\/jats:italic> are associated with a different (novel) subtype of SCD mainly characterized by severe rib anomalies but lacking clear segmentation defects of the vertebral bodies.<\/jats:p>","DOI":"10.1002\/ajmg.a.38668","type":"journal-article","created":{"date-parts":[[2018,4,22]],"date-time":"2018-04-22T04:10:11Z","timestamp":1524370211000},"page":"1216-1221","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Homozygous <i>DMRT2<\/i> variant associates with severe rib malformations in a newborn"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-5136","authenticated-orcid":false,"given":"Arjan","family":"Bouman","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Center Amsterdam The Netherlands"},{"name":"Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quinten","family":"Waisfisz","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jop","family":"Admiraal","sequence":"additional","affiliation":[{"name":"Department of Neonatology Emma Children's Hospital Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moniek","family":"van de Loo","sequence":"additional","affiliation":[{"name":"Department of Neonatology Emma Children's Hospital Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rick R.","family":"van Rijn","sequence":"additional","affiliation":[{"name":"Department of Radiology Academic Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra","family":"Micha","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics VU University Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roelof\u2010Jan","family":"Oostra","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Embryology &amp; Physiology Academic Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge B.","family":"Mathijssen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Academic Medical Center Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,4,21]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/74307"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00429-004-0408-z"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33471"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32217"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320400304"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1319"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30244"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu534"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33361"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.F.01085"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1302\/0301-620X.70B1.3339042"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24033"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2005.11.027"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/498879"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36073"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddn272"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt012"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.BRS.0000128761.72844.AB"},{"key":"e_1_2_12_21_1","unstructured":"Turnpenny P. D. Sloman M. Dunwoodie S. & ICVAS (International Consortium for Vertebral Anomalies and Scoliosis). (2017). Spondylocostal dysostosis autosomal recessive. InM. P.Adam H. H.Ardinger R. A.Pagon S. E.Wallace L. J. H.Bean K.Stephens &A.Amemiya(Eds.) GeneReviews(R). 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