{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:22:31Z","timestamp":1791519751181,"version":"4.3.4"},"reference-count":26,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T00:00:00Z","timestamp":1746230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Gorlin\u2010Goltz Syndrome (GGS) is a rare autosomal dominant genetic disorder encompassing a diverse range of clinical manifestations, including congenital anomalies and predisposition to cancer. Pathogenic variants in\n                    <jats:italic>PTCH1<\/jats:italic>\n                    and\n                    <jats:italic>SUFU<\/jats:italic>\n                    account for up to 79% and 6% of cases, respectively. Currently, an estimated 15%\u201327% of individuals with a clinical diagnosis of GGS do not have a pathogenic variant identified in either gene. We report on a 17\u2010year\u2010old female referred to the Undiagnosed Disease Network with a clinical diagnosis of GGS that manifested as both classic and unusual findings, including isolated hypogonadotropic hypogonadism and anosmia (Kallmann syndrome), orofacial cleft, and abnormal semicircular canals (SCC). Prior genetic testing, including a targeted gene panel, genomic microarray, exome sequencing, and genome sequencing, was non\u2010diagnostic, although these studies identified a variant of uncertain significance in\n                    <jats:italic>CHD7<\/jats:italic>\n                    , which may have contributed to elements of the phenotype (e.g., abnormal SCC). Reanalysis of genome sequencing data using research analytic methods, together with karyotyping, FISH, and Sanger sequencing, identified a novel\n                    <jats:italic>de novo<\/jats:italic>\n                    paracentric inversion that truncated\n                    <jats:italic>PTCH1<\/jats:italic>\n                    . These findings underscore the value of in\u2010depth phenotype\u2010guided genomic analysis, including chromosomal structural variants, as well as the occurrence of possible dual genetic diagnoses in the same individuals. Moreover, the definitive diagnosis provided the patient and family with a firmer basis for management and counseling.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64108","type":"journal-article","created":{"date-parts":[[2025,5,3]],"date-time":"2025-05-03T06:48:13Z","timestamp":1746254893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Worth the Effort: Lessons for Discovery and Care From an Unusual Case of Gorlin Syndrome"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-3576","authenticated-orcid":false,"given":"V.","family":"Taliercio","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3366-5194","authenticated-orcid":false,"given":"J.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utah  Salt Lake City Utah USA"},{"name":"ARUP Laboratories  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. E.","family":"Boyden","sequence":"additional","affiliation":[{"name":"Utah Center for Genetic Discovery, Department of Human Genetics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utah  Salt Lake City Utah USA"},{"name":"ARUP Laboratories  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Bayrak\u2010Toydemir","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Utah  Salt Lake City Utah USA"},{"name":"ARUP Laboratories  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Pflaum","sequence":"additional","affiliation":[{"name":"ARUP Laboratories  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Palumbos","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. 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