{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T16:30:03Z","timestamp":1791304203511,"version":"4.3.1"},"reference-count":30,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"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":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Pediatric patients of autosomal dominant early onset osteoporosis conferred by heterozygous mutation in the <jats:italic>WNT1<\/jats:italic> (OMIM: 615221) were rarely reported, and therapy in pediatrics is relatively inexperienced. The clinical and genotypic characteristics and treatment process of four children with osteoporosis caused by <jats:italic>WNT1<\/jats:italic> monoallelic variation were analyzed. The patients admitted from June 2023 to January 2024. All patients presented multiple vertebral compression fracture, two of them experienced recurrent peripheral fragility fractures. The age of the first fractures occur between 2\u2009years and 12\u2009years. Lumber BMD by dual\u2010energy X\u2010ray absorptiometry were decreased (height adjusted <jats:italic>z<\/jats:italic> score of \u22128.06 to \u22123.50). Four monoallelic variants in <jats:italic>WNT1<\/jats:italic> (c.505G&gt;T, c.616G&gt;A, c.677C&gt;T and c. 506G&gt;A with transcript ID. NM_005430.4) were identified in the probands, and relatives carrying mutations presented with a bone phenotype, consistent with autosomal dominant inheritance. Novel variant c.616G&gt;A was analyzed by 3D protein structural modeling. Subsequent to the treatment of zelodronic acid on all four patients, lumbar BMD improvement by 0.061\u20130.251\u2009g\/cm<jats:sup>2<\/jats:sup>. Our data showed that the age of onset of osteoporosis by monoallelic variants in <jats:italic>WNT1<\/jats:italic> is significantly earlier than the age of onset in the general population. Severe osteoporosis is also exhibited in pediatric patients, not just in aging patients with <jats:italic>WNT1<\/jats:italic> variant. Zoledronic acid treatment is effective in short\u2010term observation for pediatric patients with improvement of bone pain and BMD, and no more facture during treatment.<\/jats:p>","DOI":"10.1002\/ajmg.a.63987","type":"journal-article","created":{"date-parts":[[2025,1,9]],"date-time":"2025-01-09T06:04:46Z","timestamp":1736402686000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Osteoporosis Caused by Monoallelic Variant of <scp>WNT1<\/scp> Gene in Four Pediatric Patients"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6570-8160","authenticated-orcid":false,"given":"Qiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism Beijing Children's Hospital, Capital Medical University  Beijing 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Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism Beijing Children's Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Ya","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism Beijing Children's Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1262-7383","authenticated-orcid":false,"given":"Chun\u2010Xiu","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism Beijing Children's Hospital, Capital Medical University  Beijing 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