{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T07:49:53Z","timestamp":1753861793318,"version":"3.41.2"},"reference-count":23,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,1,2]],"date-time":"2025-01-02T00:00:00Z","timestamp":1735776000000},"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>Hajdu\u2013Cheney syndrome (HCS), caused by a heterozygous gain of function variant of the <jats:italic>NOTCH2<\/jats:italic> gene, is a rare skeletal dysplasia. Although the main presentation is acro\u2010osteolysis, osteoporosis, and facial dysmorphism, having a wide range of clinical manifestations creates diagnostic difficulties. Here, a 15\u2010year\u2010old male patient with HCS who had no complaints until this age except for two short bone fractures and one vertebral collapse fracture due to a fall was reported. The patient presented with acro\u2010osteolysis, facial anomalies, skull deformity, and osteoporosis. The clinical diagnosis of HCS was supported by a positive genetic test of a novel de novo heterozygous pathogenic variant in exon 34 of <jats:italic>NOTCH2<\/jats:italic> c.6614dupAfs*. Zoledronic acid treatment was applied for 2\u2009years, and the patient responded well to the treatment, showing signs of improved bone density and improvement in vertebral height. We identified a novel <jats:italic>NOTCH2<\/jats:italic> gene variant related to HCS. Our findings could extend phenotypic spectrum and genotype\u2013phenotype correlations. The results of this case report support that antiresorptive treatment with zoledronic acid increased bone mineral density. Nevertheless, because of the low prevalence of the syndrome and the small number of reported cases, further studies are required to understand the syndrome better and establish treatment guidelines.<\/jats:p>","DOI":"10.1002\/ajmg.a.63985","type":"journal-article","created":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T06:48:36Z","timestamp":1735886916000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hajdu\u2013Cheney Syndrome, a Rare Cause of Acro\u2010Osteolysis and Osteoporosis With Zoledronic Acid Experience"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7888-7295","authenticated-orcid":false,"given":"Gonul","family":"Buyukyilmaz","sequence":"first","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara Bilkent City Hospital  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5453-8621","authenticated-orcid":false,"given":"Mehmet","family":"Adiguzel","sequence":"additional","affiliation":[{"name":"Department of Radiology Dr. Burhan Nalbanto\u011flu State Hospital  Nicosia Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2160-9838","authenticated-orcid":false,"given":"Fatih","family":"Gurbuz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Ankara Yildirim Beyazit University Faculty of Medicine  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0522-1809","authenticated-orcid":false,"given":"Esra","family":"K\u0131l\u0131c","sequence":"additional","affiliation":[{"name":"Department of Pediatric Genetics University of Health Sciences, Ankara City Hospital  Ankara Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,1,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2016.08.025"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amsu.2021.01.041"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911374"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22031325"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10067\u2010016\u20103459\u20107"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.08.002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010014\u20100200\u2010y"},{"key":"e_1_2_9_9_1","first-page":"595","article-title":"Acro\u2010Osteolysis","volume":"94","author":"Cheney W. D.","year":"1965","journal-title":"American Journal of Roentgenology, Radium Therapy, and Nuclear Medicine"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00431\u2010022\u201004743\u2010x"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17176174"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12030566"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/mcd.0000000000000034"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010020\u201002446\u20107"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63013"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.00299\u201008"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014\u20102173"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1259\/0007\u20101285\u201021\u2010241\u201042"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.21546"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440\u20101673.2006.01616.x"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010018\u20100795\u20105"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2017\u201001102"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2012.10.027"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891\u2010020\u20103181\u20100"}],"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.63985","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T08:12:02Z","timestamp":1743840722000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,2]]},"references-count":23,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1002\/ajmg.a.63985"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63985","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2025,1,2]]},"assertion":[{"value":"2024-09-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-01-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63985"}}