{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T19:42:31Z","timestamp":1768419751748,"version":"3.49.0"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T00:00:00Z","timestamp":1658188800000},"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":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>ERF<\/jats:italic>\u2010related craniosynostosis syndrome type 4 (CRS4, OMIM #600775) is a rare autosomal dominant malformation syndrome, caused by pathogenic variants in the <jats:italic>ERF<\/jats:italic> gene and characterized by craniosynostosis, developmental delay, and dysmorphic features such as hypertelorism, exophthalmos, depressed nasal bridge, and retrognathia. So far, there are mostly individual reports and only a few descriptions of families with more than two affected patients, allowing statements about the penetrance of a certain variant and its variability only to a limited extent. In this study, we report an in\u2010depth analysis of the clinical course of six family members from three generations with the novel heterozygous nonsense variant c.286A&gt;T (p.Lys96*) in the <jats:italic>ERF<\/jats:italic> gene. At the time of examination, all of the six patients showed mild dysmorphic features and brachydactyly, five were overweight\/obese and had delayed speech development, and four were short in stature. Hyperactivity, a short concentration span and a history of learning difficulties were found in half of the affected family members. To this day, none of the patients developed increased intracranial hypertension that would require surgical intervention. This work provides further information on the expressive variability of an <jats:italic>ERF<\/jats:italic> variant in six members of one family and focuses on the need for close neuropediatric surveillance.<\/jats:p>","DOI":"10.1002\/ajmg.a.62900","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T18:39:15Z","timestamp":1658255955000},"page":"2969-2975","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Intrafamilial variability in six family members with <i>ERF<\/i>\u2010related craniosynostosis syndrome type 4"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0320-3420","authenticated-orcid":false,"given":"Marina K.","family":"Moddemann","sequence":"first","affiliation":[{"name":"Department of Human Genetics Bioscientia Institute for Medical Diagnostics  Ingelheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Kieslich","sequence":"additional","affiliation":[{"name":"Division of Neurology, Neurometabolics and Prevention, Department of Pediatrics, Faculty of Medicine University of Frankfurt  Frankfurt am Main Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Koenig","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Bioscientia Institute for Medical Diagnostics  Ingelheim Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,7,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-017-2531-x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-104143"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2021.03.005"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14230"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32208"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37218"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38846"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61073"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.0c00774"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-020-01015-z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38159"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.214"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.6065\/apem.2040064.032"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2539"},{"key":"e_1_2_9_17_1","unstructured":"WengerT M. D. EvansK. (1993\u20132020).FGFR craniosynostosis syndromes overview. Retrieved fromhttps:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1455\/. Retrieved November 23 2020 from In: Adam MP Ardinger HH Pagon RA et al. editors. GeneReviews\u00aehttps:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1455\/"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2009-3491"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0000000000000542"},{"key":"e_1_2_9_20_1","unstructured":"Yadav A. &Hopkin R.(2017).ERF\u2010related Craniosynostosis syndrome and short stature: A new association? Paper presented at the ACMG Annual Clinical Genetics Meeting."}],"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.62900","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62900","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62900","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T06:43:32Z","timestamp":1708497812000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62900"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,19]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2022,10]]}},"alternative-id":["10.1002\/ajmg.a.62900"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62900","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,19]]},"assertion":[{"value":"2022-04-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}