{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T11:57:36Z","timestamp":1769255856946,"version":"3.49.0"},"reference-count":9,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T00:00:00Z","timestamp":1729468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ek0109549s2503"],"award-info":[{"award-number":["23ek0109549s2503"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23ek0109549s0203"],"award-info":[{"award-number":["23ek0109549s0203"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Radio\u2010Tartaglia syndrome (RATARS) (MIM#619312) is a genetic disorder caused by heterozygous truncating variants of <jats:italic>SPEN<\/jats:italic> on chromosome 1p36. This syndrome is extremely rare, with only 34 cases reported to date. RATARS is characterized by developmental delay, hypotonia, and intellectual disability. In this study, we report a Japanese girl with psychomotor delay, hypotonia, and facial features resembling Down syndrome (DS). We identified a <jats:italic>de novo<\/jats:italic> heterozygous pathogenic variant of <jats:italic>SPEN<\/jats:italic> and diagnosed her with RATARS. The patient was born at 38\u2009weeks and 1\u2009day of gestational age, weighing 2598\u2009g, without respiratory or feeding difficulties. We first considered DS as a differential diagnosis based on the developmental delay with hypotonia and facial features, including an upslanted palpebral fissure, hypertelorism, epicanthus folds, and a low nose; however, it was ruled out after cytogenetic testing. Microarray analysis revealed no pathogenic aberrations. We performed trio\u2010based whole exome sequencing and identified a recurrent pathogenic variant of <jats:italic>SPEN<\/jats:italic>:NM_015001.3:c.6223_6227del, p.(Ser2075GlufsTer46). Although some features of RATARS have been reported to be similar to those of 1p36 deletion syndrome, facial similarity to DS was a characteristic of our case. Whether this feature is unique to the patient or relatively common in individuals with RATARS should be discussed further as more cases of individuals with RATARS are reported.<\/jats:p>","DOI":"10.1002\/ajmg.a.63910","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T12:58:58Z","timestamp":1729515538000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Features of a Japanese Girl With Radio\u2010Tartaglia Syndrome due to a <i>SPEN<\/i> Truncating Variant"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7993-1964","authenticated-orcid":false,"given":"Eriko","family":"Nishi","sequence":"first","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kumiko","family":"Yanagi","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuhiko","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics Osaka Women's and Children's Hospital  Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0281-9610","authenticated-orcid":false,"given":"Tadashi","family":"Kaname","sequence":"additional","affiliation":[{"name":"Department of Genome Medicine National Center for Child Health and Development  Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,10,21]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010020\u20101974\u20109"},{"key":"e_1_2_11_3_1","first-page":"266","volume-title":"Smith's Recognizable Patterns of Human Malformation","author":"Jones K. L.","year":"2022"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31407"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101819.2009.01931"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038\u2010019\u20100619\u2010z"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.01.015"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.871201"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M314098200"}],"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.63910","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T12:16:33Z","timestamp":1748348193000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,21]]},"references-count":9,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["10.1002\/ajmg.a.63910"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63910","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,21]]},"assertion":[{"value":"2024-07-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63910"}}