{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:24:07Z","timestamp":1788459847248,"version":"build-2803163510"},"reference-count":18,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T00:00:00Z","timestamp":1540166400000},"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":[[2018,12]]},"abstract":"<jats:p>Wolf\u2010Hirschhorn syndrome (WHS) is a microdeletion syndrome characterized by distinctive facial features consisting of \u201cGreek warrior helmet\u201d appearance, prenatal and postnatal growth deficiency, developmental disability, and seizures. This disorder is caused by heterozygous deletions on chromosome 4p16.3 often identified by cytogenetic techniques. Many groups have attempted to identify the critical region within this deletion to establish which genes are responsible for WHS. Herein, clinical whole exome sequencing (WES) was performed on a child with developmental delays, mild facial dysmorphisms, short stature, failure to thrive, and microcephaly, and revealed a de novo frameshift variant, c.1676_1679del (p.Arg559Tfs*38), in <jats:italic>WHSC1<\/jats:italic> (<jats:italic>NSD2<\/jats:italic>). While <jats:italic>WHSC1<\/jats:italic> falls within the WHS critical region, individuals with only disruption of this gene have only recently been described in the literature. Loss\u2010of\u2010function de novo variations in <jats:italic>WHSC1<\/jats:italic> were identified in large developmental delay, autism, diagnostic, and congenital cardiac cohorts, as well as recent case reports, suggesting that de novo loss\u2010of\u2010function <jats:italic>WHSC1<\/jats:italic> variants may be related to disease. These findings, along with our patient suggest that loss\u2010of\u2010function variation in <jats:italic>WHSC1<\/jats:italic> may lead to a mild form of Wolf\u2010Hirschhorn syndrome, and also may suggest that the developmental delays, facial dysmorphisms, and short stature seen in WHS may be due to disruption of <jats:italic>WHSC1<\/jats:italic> gene.<\/jats:p>","DOI":"10.1002\/ajmg.a.40498","type":"journal-article","created":{"date-parts":[[2018,10,22]],"date-time":"2018-10-22T08:09:41Z","timestamp":1540195781000},"page":"2798-2802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Developmental delay and failure to thrive associated with a loss\u2010of\u2010function variant in <i>WHSC1 (NSD2)<\/i>"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9283-3151","authenticated-orcid":false,"given":"Nicole J.","family":"Boczek","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine and Pathology; Genomics Laboratory Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie A.","family":"Lahner","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology; Genomics Laboratory Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thuy\u2010mi","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology; Genomics Laboratory Mayo Clinic  Rochester Minnesota"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Ferber","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology; Genomics Laboratory Mayo Clinic  Rochester Minnesota"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Hasadsri","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology; Genomics Laboratory Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik C.","family":"Thorland","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology; Genomics Laboratory Mayo Clinic  Rochester Minnesota"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyv","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology; Genomics Laboratory Mayo Clinic  Rochester Minnesota"},{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralitza H.","family":"Gavrilova","sequence":"additional","affiliation":[{"name":"Department of Clinical Genomics Mayo Clinic  Rochester Minnesota"},{"name":"Department of Neurology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,10,22]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31449"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.30187"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13772"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0014-8"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103626"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac9396"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.33121"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4352"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-018-0464-5"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1821-8"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08086"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1203"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3638"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/7.7.1071"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature21062"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13316"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4524"}],"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.40498","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.40498","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T09:49:02Z","timestamp":1694684942000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.40498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,22]]},"references-count":18,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["10.1002\/ajmg.a.40498"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.40498","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,22]]},"assertion":[{"value":"2018-06-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}