{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T02:56:05Z","timestamp":1785207365694,"version":"3.55.0"},"reference-count":14,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T00:00:00Z","timestamp":1537747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002385","name":"Ministry of Higher Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002385","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HD070394"],"award-info":[{"award-number":["P01 HD070394"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 AR068069"],"award-info":[{"award-number":["U54 AR068069"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K01 AR069002"],"award-info":[{"award-number":["K01 AR069002"]}],"id":[{"id":"10.13039\/100000002","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":[[2018,11]]},"abstract":"<jats:p>Osteogenesis imperfecta (OI) is a family of heritable disorders of bone fragility. Most individuals with OI have mutations in the genes encoding type I collagen; at least 17 other genes have been associated with OI. Biallelic loss\u2010of\u2010function mutations in <jats:italic>WNT1<\/jats:italic> cause severe OI. Heterozygous missense variants in <jats:italic>WNT1<\/jats:italic> are responsible for early\u2010onset osteoporosis with variable bone phenotypes. Herein, we report a third\u2010generation family with four affected individuals, some presenting with multiple low\u2010impact fractures in childhood and others presenting with early\u2010onset osteoporosis without a striking fracture history. A <jats:italic>WNT1<\/jats:italic> variant (c. 1051 &gt; C; p.Trp351Arg) was identified in the proband and segregated with a bone phenotype in three additional family members, consistent with autosomal dominant inheritance. In the proband, whole genome sequencing also revealed a de novo duplication (434 kb) of 22q11.2 that involves 25 genes, 4 of which are associated with human disease when haploinsufficient. Though smaller than the typical (1.5 Mb) 22q11.2 duplication, the duplication in the proband may be responsible for additional nonosseous aspects of his phenotype (hypotonia, developmental delay, small genitalia, strabismus, and depression in preadolescence). This case demonstrates the variability of bone phenotype conferred by a <jats:italic>WNT1<\/jats:italic> variant and extends the spectrum of bone phenotypes associated with heterozygous <jats:italic>WNT1<\/jats:italic> mutations.<\/jats:p>","DOI":"10.1002\/ajmg.a.40347","type":"journal-article","created":{"date-parts":[[2018,9,24]],"date-time":"2018-09-24T09:10:54Z","timestamp":1537780254000},"page":"2419-2424","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Heterozygous <i>WNT1<\/i> variant causing a variable bone phenotype"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4113-5879","authenticated-orcid":false,"given":"Shatha","family":"Alhamdi","sequence":"first","affiliation":[{"name":"University of California  San Diego La Jolla California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Chien","family":"Lee","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimul","family":"Chowdhury","sequence":"additional","affiliation":[{"name":"Rady Children's Institute for Genomic Medicine  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Byers","sequence":"additional","affiliation":[{"name":"University of Washington  Seattle Washington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Gottschalk","sequence":"additional","affiliation":[{"name":"University of California  San Diego La Jolla California"},{"name":"Divisions of Endocrinology Rady Children's Hospital San Diego  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Taft","sequence":"additional","affiliation":[{"name":"Illumina Clinical Services Laboratory Illumina Inc.  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Sang","family":"Joeng","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan H.","family":"Lee","sequence":"additional","affiliation":[{"name":"Baylor College of Medicine  Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynne M.","family":"Bird","sequence":"additional","affiliation":[{"name":"University of California  San Diego La Jolla California"},{"name":"Divisions of Dysmorphology\/Genetics Rady Children's Hospital San Diego  San Diego California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,9,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/382638a0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101567"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-101750"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-10-48"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1159\/000439566"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.02.010"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1215458"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2841"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2014.06.041"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.02.009"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.10.001"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00198-016-3723-3"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81925-X"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(03)00240-9"}],"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.40347","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.40347","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T13:15:21Z","timestamp":1694697321000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.40347"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9,24]]},"references-count":14,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2018,11]]}},"alternative-id":["10.1002\/ajmg.a.40347"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.40347","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9,24]]},"assertion":[{"value":"2017-11-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-09-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}