{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T23:09:28Z","timestamp":1792192168049,"version":"4.4.0"},"reference-count":10,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"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":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>EVEN\u2010PLUS syndrome is a rare condition characterized by its involvement of the <jats:bold>E<\/jats:bold>piphyses, <jats:bold>V<\/jats:bold>ertebrae, <jats:bold>E<\/jats:bold>ars, and <jats:bold>N<\/jats:bold>ose, <jats:bold>PLUS<\/jats:bold> other associated findings. We report here the fifth case of EVEN\u2010PLUS syndrome with novel variants c.818\u2009T\u2009&gt;\u2009G (p.L273X) and c.955C\u2009&gt;\u2009T (p.L319F) in the <jats:italic>HSPA9<\/jats:italic> gene identified through whole\u2010exome sequencing. The patient is the first male known to be affected and presented with additional features not previously described with EVEN\u2010PLUS syndrome. These features include agenesis of the septum pellucidum, a short chest and sternum, 13 pairs of ribs, a single hemivertebra, laterally displaced nipples, hydronephrosis, unilateral cryptorchidism, unilateral single palmar crease, bilateral clubfoot, and hypotonia. qPCR analysis provides supporting evidence for a nonsense\u2010mediated decay mechanism for the <jats:italic>HSPA9<\/jats:italic> truncating variant. In silico 3D modeling supports the pathogenicity of the c.955C\u2009&gt;\u2009T (p.L319F) missense variant. The study presented here further describes the syndrome and broadens its mutational and phenotypic spectrum. Our study also lends support to <jats:italic>HSPA9<\/jats:italic> variants as the underlying etiology of EVEN\u2010PLUS syndrome and ultimately provides a better understanding of the molecular basis of the condition.<\/jats:p>","DOI":"10.1002\/ajmg.a.61808","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T08:45:22Z","timestamp":1598949922000},"page":"2501-2507","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["<scp>EVEN\u2010PLUS<\/scp> syndrome: A case report with novel variants in <scp><i>HSPA9<\/i><\/scp> and evidence of <scp><i>HSPA9<\/i><\/scp> gene dysfunction"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9528-7571","authenticated-orcid":false,"given":"Georgianne","family":"Younger","sequence":"first","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Vetrini","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8312-8995","authenticated-orcid":false,"given":"David D.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ty C.","family":"Lynnes","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Treat","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria M.","family":"Pratt","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfredo","family":"Torres\u2010Martinez","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1379\/CSC-144R.1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0117170"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4149\/av_2013_01_3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/348137a0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.9b00071"},{"issue":"2","key":"e_1_2_9_8_1","first-page":"e1000350","article-title":"Postural and gait abnormality in even plus syndrome","volume":"12","author":"Nagrani D. G.","year":"2018","journal-title":"The Journal of Molecular and Genetic Medicine"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep17154"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/371768a0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.12.003"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61808","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61808","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61808","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T05:54:53Z","timestamp":1693720493000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61808"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":10,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/ajmg.a.61808"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61808","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]},"assertion":[{"value":"2020-04-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}