{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T09:46:32Z","timestamp":1785836792929,"version":"3.56.0"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T00:00:00Z","timestamp":1776384000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Grange syndrome is a rare early\u2010onset multisystem disorder characterized by multifocal steno\u2010occlusive arterial disease, bone fragility, congenital cardiac anomalies, skeletal manifestations, and intellectual disability, caused by biallelic loss\u2010of\u2010function variants in\n                    <jats:italic>YY1AP1<\/jats:italic>\n                    . We report eight affected individuals (six females, two males) from a single consanguineous family. Molecular analysis included exome sequencing in three patients (P1, P5, and P7) and targeted next\u2010generation sequencing in one patient (P8), with Sanger sequencing performed for segregation analysis and parental carrier testing. A novel biallelic\n                    <jats:italic>YY1AP1<\/jats:italic>\n                    variant (NM_001198903.1: c.2531_2532del; p.E844Gfs*34) was identified in all affected individuals. One patient, a 4\u2010month\u2010old female, harbored an additional novel biallelic pathogenic variant in\n                    <jats:italic>CLMP<\/jats:italic>\n                    (NM_024769.5: c.167dup; p.N56Kfs*2), consistent with a dual molecular diagnosis. The most common presenting feature was multiple fractures, observed in six patients. The mean age at first fracture was 3.6\u2009\u00b1\u20091.7\u2009years, and the mean baseline bone mineral density (BMD)\n                    <jats:italic>Z<\/jats:italic>\n                    \u2010score was \u22124.1\u2009\u00b1\u20091.6. Three patients received intravenous bisphosphonate therapy for at least 2\u2009years, resulting in improvement of mean BMD\n                    <jats:italic>Z<\/jats:italic>\n                    \u2010scores from \u22124.9\u2009\u00b1\u20091.9 to \u22122.4\u2009\u00b1\u20090.7. This study represents the first Grange syndrome cohort reported from T\u00fcrkiye and expands the clinical spectrum by demonstrating marked phenotypic variability, multisystem involvement, and potential benefit of bisphosphonate therapy in patients with significant bone fragility.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.70170","type":"journal-article","created":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T03:45:15Z","timestamp":1776483915000},"page":"2036-2051","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel\n                    <scp>\n                      <i>YY1AP1<\/i>\n                    <\/scp>\n                    Variant in Grange Syndrome: Clinical and Molecular Findings in Eight Individuals With a Dual Molecular Diagnosis Involving CLMP in One Patient"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9770-284X","authenticated-orcid":false,"given":"Ak\u00e7ahan","family":"Akal\u0131n","sequence":"first","affiliation":[{"name":"Department of Pediatric Genetics Diyarbak\u0131r Children's Hospital  Diyarbak\u0131r Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7619-9365","authenticated-orcid":false,"given":"Veysel","family":"\u00d6z","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Diyarbak\u0131r Children's Hospital  Diyarbak\u0131r Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2443-4378","authenticated-orcid":false,"given":"Ay\u015fe Seda","family":"P\u0131narba\u015f\u0131","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology Diyarbak\u0131r Children's Hospital  Diyarbak\u0131r Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1557-6040","authenticated-orcid":false,"given":"\u015eervan","family":"\u00d6zalkak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Diyarbak\u0131r Children's Hospital  Diyarbak\u0131r Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2614-8879","authenticated-orcid":false,"given":"Mehmet Salih","family":"Karaca","sequence":"additional","affiliation":[{"name":"Department of Radiology Gazi Ya\u015fargil Training and Research Hospital  Diyarbak\u0131r Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-3856","authenticated-orcid":false,"given":"Ruken","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology Diyarbak\u0131r Children's Hospital  Diyarbak\u0131r Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,17]]},"reference":[{"issue":"5","key":"e_1_2_12_2_1","first-page":"10","article-title":"SWI\/SNF Chromatin Remodeling Complex in Regulating Mesenchymal Stem Cell Lineage Specification","volume":"6","author":"Chen D.","year":"2015","journal-title":"Journal of Tissue Science & Engineering"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61379"},{"key":"e_1_2_12_4_1","unstructured":"Duker A. 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