{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:02:53Z","timestamp":1792612973812,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T00:00:00Z","timestamp":1585094400000},"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":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The clinical and radiological spectrum of spondylocostal dysostosis syndromes encompasses distinctive costo\u2010vertebral anomalies. <jats:italic>RIPPLY2<\/jats:italic> biallelic pathogenic variants were described in two distinct cervical spine malformation syndromes: Klippel\u2013Feil syndrome and posterior cervical spine malformation. RIPPLY2 is involved in the determination of rostro\u2010caudal polarity and somite patterning during development. To date, only four cases have been reported. The current report aims at further delineating the posterior malformation in three new patients. Three patients from two unrelated families underwent clinical and radiological examination through X\u2010ray, 3D computed tomography and brain magnetic resonance imaging. After informed consent was obtained, family\u2010based whole exome sequencing (WES) was performed. Complex vertebral segmentation defects in the cervico\u2010thoracic spine were observed in all patients. WES led to the identification of the homozygous splicing variant c.240\u20104T&gt;G in all subjects. This variant is predicted to result in aberrant splicing of Exon 4. The current report highlights a subtype of cervical spine malformation with major atlo\u2010axoidal malformation compromising spinal cord integrity. This distinctive mutation\u2010specific pattern of malformation differs from Klippel\u2013Feil syndrome and broadens the current classification, defining a sub\u2010type of <jats:italic>RIPPLY2<\/jats:italic>\u2010related skeletal disorder. Of note, the phenotype of one patient overlaps with oculo\u2010auriculo\u2010vertebral spectrum disorder.<\/jats:p>","DOI":"10.1002\/ajmg.a.61549","type":"journal-article","created":{"date-parts":[[2020,3,25]],"date-time":"2020-03-25T08:35:45Z","timestamp":1585125345000},"page":"1466-1472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Congenital posterior cervical spine malformation due to biallelic c.240\u20104T&gt;G <i>RIPPLY2<\/i> variant: A discrete entity"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1165-0872","authenticated-orcid":false,"given":"Margaux","family":"Serey\u2010Gaut","sequence":"first","affiliation":[{"name":"Centre de g\u00e9n\u00e9tique humaine Universit\u00e9 de Franche Comt\u00e9  Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2194-7239","authenticated-orcid":false,"given":"Marcello","family":"Scala","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"Department of Neurosurgery IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Reversade","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, A*STAR  Singapore Singapore"},{"name":"Laboratory of Human Embryology and Genetics Institute of Medical Biology, A*STAR  Singapore Singapore"},{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyse","family":"Ruaud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris  Paris France"},{"name":"Service de g\u00e9n\u00e9tique clinique, AP\u2010HP, H\u00f4pital Robert Debr\u00e9  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Cabrol","sequence":"additional","affiliation":[{"name":"Centre de g\u00e9n\u00e9tique humaine Universit\u00e9 de Franche Comt\u00e9  Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Musacchia","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalaura","family":"Torella","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Naples Italy"},{"name":"Department of Precision Medicine University of Campania \u2018Luigi Vanvitelli\u2019  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8724-6721","authenticated-orcid":false,"given":"Andrea","family":"Accogli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health University of Genoa  Genoa Italy"},{"name":"Department of Neurosurgery IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Escande\u2010Beillard","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cell Biology, A*STAR  Singapore Singapore"},{"name":"Medical Genetics Department Ko\u00e7 University School of Medicine  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Langlais","sequence":"additional","affiliation":[{"name":"Department of Pediatric Orthopedic Surgery University Hospital, Universit\u00e9 de Franche Comt\u00e9  Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Piatelli","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Consales","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Nigro","sequence":"additional","affiliation":[{"name":"Telethon Institute of Genetics and Medicine  Naples Italy"},{"name":"Department of Precision Medicine University of Campania \u2018Luigi Vanvitelli\u2019  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Capra","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery IRCCS Istituto Giannina Gaslini  Genoa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lionel","family":"Van Maldergem","sequence":"additional","affiliation":[{"name":"Centre de g\u00e9n\u00e9tique humaine Universit\u00e9 de Franche Comt\u00e9  Besan\u00e7on France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2014-102476"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.21342"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.05.017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197153030-00015"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1148\/103.3.581"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197961040-00015"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4103\/jpn.JPN_154_16"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nec.2007.05.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-198668020-00002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.009266"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/02688699908540618"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.003728"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spinee.2004.10.044"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37263"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mod.2018.06.001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.4184\/asj.2016.10.1.170"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu534"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2011.04.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jemermed.2018.09.044"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.000836"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61366"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197557060-00025"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2017.10.166"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.11.003"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00005.2017"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2010.03.015"},{"issue":"2","key":"e_1_2_9_28_1","first-page":"250","article-title":"Congenital absence of the posterior elements of C2 vertebra: A case report","volume":"51","author":"Trivedi P.","year":"2003","journal-title":"Neurology India"},{"key":"e_1_2_9_29_1","volume-title":"GeneReviews\u00ae","author":"Turnpenny P. D.","year":"2010"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107928"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2015.01.020"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33068"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.61549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61549","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61549","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61549","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T08:48:02Z","timestamp":1693990082000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61549"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,25]]},"references-count":31,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1002\/ajmg.a.61549"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61549","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,25]]},"assertion":[{"value":"2019-11-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-02-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}