{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:02:49Z","timestamp":1792612969580,"version":"4.5.0"},"reference-count":46,"publisher":"BMJ","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[2003,5]]},"abstract":"<jats:p>The spondylocostal dysostoses (SCD) are a group of disorders characterised by multiple vertebral segmentation defects and rib anomalies. SCD can either be sporadic or familial, and can be inherited in either autosomal dominant or recessive modes. We have previously shown that recessive forms of SCD can be caused by mutations in the delta-like 3 gene, <jats:italic>DLL3<\/jats:italic>. Here, we have sequenced <jats:italic>DLL3<\/jats:italic> in a series of SCD cases and identified 12 mutations in a further 10 families. These include 10 novel mutations in exons 4\u20138, comprising nonsense, missense, frameshift, splicing, and in frame insertion mutations that are predicted to result in either the truncation of the mature protein in the extracellular domain, or affect highly conserved amino acid residues in the epidermal growth factor-like repeats of the protein. The affected cases represent diverse ethnic backgrounds and six come from traditionally consanguineous communities. In all affected subjects, the radiological phenotype is abnormal segmentation throughout the entire vertebral column with smooth outlines to the vertebral bodies in childhood, for which we suggest the term \u201cpebble beach sign\u201d. This is a very consistent phenotype-genotype correlation and we suggest the designation SCD type 1 for the AR form caused by mutations in the <jats:italic>DLL3<\/jats:italic> gene.<\/jats:p>","DOI":"10.1136\/jmg.40.5.333","type":"journal-article","created":{"date-parts":[[2003,5,13]],"date-time":"2003-05-13T19:54:11Z","timestamp":1052855651000},"page":"333-339","source":"Crossref","is-referenced-by-count":129,"title":["Novel mutations in <i>DLL3<\/i>, a somitogenesis gene encoding a ligand for the Notch signalling pathway, cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis"],"prefix":"10.1136","volume":"40","author":[{"given":"P D","family":"Turnpenny","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N","family":"Whittock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Dunwoodie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Kusumi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Ellard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2003,5,1]]},"reference":[{"key":"2025100520193995000_40.5.333.1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19960202)61:4<310::AID-AJMG3>3.0.CO;2-Y"},{"key":"2025100520193995000_40.5.333.2","first-page":"948","volume":"45","year":"1968","journal-title":"Am J Med Genet"},{"key":"2025100520193995000_40.5.333.3","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.25.12.831"},{"key":"2025100520193995000_40.5.333.4","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1111\/j.1399-0004.1989.tb03196.x","volume":"36","year":"1989","journal-title":"Clin Genet"},{"key":"2025100520193995000_40.5.333.5","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320350215"},{"key":"2025100520193995000_40.5.333.6","first-page":"326","volume":"18","year":"1969","journal-title":"Birth Defects"},{"key":"2025100520193995000_40.5.333.7","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1111\/j.1399-0004.1971.tb00270.x","volume":"2","year":"1971","journal-title":"Clin Genet"},{"key":"2025100520193995000_40.5.333.8","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1111\/j.1469-8749.1973.tb04891.x","volume":"15","year":"1973","journal-title":"Dev Med Child Neurol"},{"key":"2025100520193995000_40.5.333.9","doi-asserted-by":"publisher","DOI":"10.1148\/112.3.673"},{"key":"2025100520193995000_40.5.333.10","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.1399-0004.1978.tb01183.x","volume":"13","year":"1978","journal-title":"Clin Genet"},{"key":"2025100520193995000_40.5.333.11","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1399-0004.1981.tb00662.x","volume":"19","year":"1981","journal-title":"Clin Genet"},{"key":"2025100520193995000_40.5.333.12","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.28.1.27"},{"key":"2025100520193995000_40.5.333.13","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1111\/j.1399-0004.1992.tb03399.x","volume":"41","year":"1992","journal-title":"Clin Genet"},{"key":"2025100520193995000_40.5.333.14","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320080114"},{"key":"2025100520193995000_40.5.333.15","first-page":"135","volume":"29","year":"1982","journal-title":"Ann Pediatr"},{"key":"2025100520193995000_40.5.333.16","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-199604000-00009"},{"key":"2025100520193995000_40.5.333.17","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.15.2.123"},{"key":"2025100520193995000_40.5.333.18","first-page":"173","volume":"33","year":"1978","journal-title":"P\u00e9diatrie"},{"key":"2025100520193995000_40.5.333.19","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1055\/s-2008-1052954","volume":"140","year":"1984","journal-title":"Fortschr Rontgenstr"},{"key":"2025100520193995000_40.5.333.20","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320510306"},{"key":"2025100520193995000_40.5.333.21","first-page":"514","volume":"69","year":"2001","journal-title":"Am J Hum Genet Suppl"},{"key":"2025100520193995000_40.5.333.22","first-page":"123","volume":"70","year":"1988","journal-title":"J Bone Jt Surg Br"},{"key":"2025100520193995000_40.5.333.23","first-page":"221","volume":"X","year":"1974","journal-title":"Birth Defects"},{"key":"2025100520193995000_40.5.333.24","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.20.6.441"},{"key":"2025100520193995000_40.5.333.25","first-page":"216","volume":"62","year":"1938","journal-title":"Bull Johns Hopkins Hosp"},{"key":"2025100520193995000_40.5.333.26","doi-asserted-by":"crossref","first-page":"3065","DOI":"10.1242\/dev.124.16.3065","volume":"124","year":"1997","journal-title":"Development"},{"key":"2025100520193995000_40.5.333.27","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1242\/dev.129.7.1795","volume":"129","year":"2002","journal-title":"Development"},{"key":"2025100520193995000_40.5.333.28","doi-asserted-by":"publisher","DOI":"10.1038\/961"},{"key":"2025100520193995000_40.5.333.29","doi-asserted-by":"publisher","DOI":"10.1038\/74307"},{"key":"2025100520193995000_40.5.333.30","doi-asserted-by":"publisher","DOI":"10.1086\/302464"},{"key":"2025100520193995000_40.5.333.31","first-page":"365","volume":"46","year":"2002","journal-title":"Int J Dev Biol"},{"key":"2025100520193995000_40.5.333.32","unstructured":"Bonaf\u00e9 L, Giunta C, Gassner M, Steinmann M, Superti-Furga A. A cluster of autosomal recessive spondylocostal dystostosis caused by three newly identified DLL3 mutations segregating in a small village. Clin Genet (in press)."},{"key":"2025100520193995000_40.5.333.33","first-page":"171","volume":"XIII","year":"1977","journal-title":"Birth Defects"},{"key":"2025100520193995000_40.5.333.34","first-page":"1614","volume":"256","year":"1963","journal-title":"C R Acad Sci [D] Paris"},{"key":"2025100520193995000_40.5.333.35","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/BF01908282","volume":"22","year":"1977","journal-title":"Jpn J Hum Genet"},{"key":"2025100520193995000_40.5.333.36","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-199710000-00008"},{"key":"2025100520193995000_40.5.333.37","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.34.5.414"},{"key":"2025100520193995000_40.5.333.38","first-page":"1364","volume":"57","year":"1995","journal-title":"Am J Hum Genet."},{"key":"2025100520193995000_40.5.333.39","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5415.770"},{"key":"2025100520193995000_40.5.333.40","doi-asserted-by":"publisher","DOI":"10.1038\/35019241"},{"key":"2025100520193995000_40.5.333.41","doi-asserted-by":"publisher","DOI":"10.1038\/35019075"},{"key":"2025100520193995000_40.5.333.42","doi-asserted-by":"publisher","DOI":"10.1038\/35098552"},{"key":"2025100520193995000_40.5.333.43","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-235"},{"key":"2025100520193995000_40.5.333.44","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-243"},{"key":"2025100520193995000_40.5.333.45","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510290331"},{"key":"2025100520193995000_40.5.333.46","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.10.1893"}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.40.5.333","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T03:19:51Z","timestamp":1759720791000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.40.5.333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,5]]},"references-count":46,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2003,5,1]]},"published-print":{"date-parts":[[2003,5]]}},"alternative-id":["10.1136\/jmg.40.5.333"],"URL":"https:\/\/doi.org\/10.1136\/jmg.40.5.333","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"value":"0022-2593","type":"print"},{"value":"1468-6244","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,5]]}}}