{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T04:23:13Z","timestamp":1791519793068,"version":"4.3.4"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Gorlin syndrome (GS) is an autosomal dominant disorder characterized by a predisposition to basal cell carcinoma and developmental defects. It is caused by pathogenic variants in the PTCH1 or SUFU genes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To ascertain the effectiveness of molecular screening in a cohort of patients with a suspicion of GS and to describe the patients\u2019 clinical and genetic characteristics.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In total, 110 patients with a suspicion of GS were studied. The patients were seen at the genetic department of Bichat University Hospital for molecular screening. The patients\u2019 clinical and paraclinical data were collected and analysed according to Evans\u2019 diagnostic criteria and were compared with molecular information.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Among 110 probands, only 56% fulfilled Evans\u2019 diagnostic criteria. Overall, 75% of the patients who fulfilled those criteria carried a pathogenic variation in PTCH1 or SUFU. We compared the clinical and paraclinical data of 54 probands carrying a PTCH1 or SUFU mutation with 56 probands without identified mutations. Among patients carrying a pathogenic variation in the PTCH1 or SUFU genes, 30\u2005years appears to be the cut-off age after which all patients have clear clinical GS. Indeed, after age 30\u2005years, all patients carrying a PTCH1 or SUFU mutation fulfilled the diagnostic criteria of Evans (82% met the clinical criteria, reaching 100% with complementary examinations such as X-rays and ultrasound). Before 30\u2005years of age, only 37% of patients with mutated genes fulfilled the clinical diagnostic criteria, reaching only 62% with simple complementary exams. We also report 22 new mutations in PTCH1.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Molecular screening of patients with GS who do not fulfil Evans\u2019 diagnostic criteria should only be offered in the first instance to patients under 30\u2005years of age. After age 30\u2005years, careful clinical examination and complementary radiological exams should be enough to eliminate the diagnosis of GS among patients who do not fulfil the diagnostic criteria.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ced\/llae210","type":"journal-article","created":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T18:31:25Z","timestamp":1716229885000},"page":"380-386","source":"Crossref","is-referenced-by-count":3,"title":["Clinical vs. molecular diagnosis of Gorlin syndrome: relevance of diagnostic criteria depends on the age of the patients"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6913-6673","authenticated-orcid":false,"given":"Agathe","family":"Hercent","sequence":"first","affiliation":[{"name":"Department of Genetics, Bichat Hospital (APHP), Reference Laboratory for the Diagnosis of Gorlin Syndrome, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizk","family":"Bennani","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Hospital (APHP), Reference Laboratory for the Diagnosis of Gorlin Syndrome, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Lafitte","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Hospital (APHP), Reference Laboratory for the Diagnosis of Gorlin Syndrome, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mickael","family":"Mary","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Hospital (APHP), Reference Laboratory for the Diagnosis of Gorlin Syndrome, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jer\u00f4me","family":"Lamoril","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Hospital (APHP), Reference Laboratory for the Diagnosis of Gorlin Syndrome, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuelle","family":"Bourrat","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Reference Centre for Rare Skin Diseases MAGEC, Saint Louis Hospital, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Kannengiesser","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Hospital (APHP), Reference Laboratory for the Diagnosis of Gorlin Syndrome, University of Paris Cit\u00e9 , Paris ,","place":["France"]},{"name":"INSERM U1152, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Tchernitchko","sequence":"additional","affiliation":[{"name":"Department of Genetics, Bichat Hospital (APHP), Reference Laboratory for the Diagnosis of Gorlin Syndrome, University of Paris Cit\u00e9 , Paris ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"2025012715573878500_llae210-B1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1056\/NEJM196005052621803","article-title":"Multiple nevoid basal-cell epithelioma, jaw cysts and bifid rib","volume":"262","author":"Gorlin","year":"1960","journal-title":"N Engl J Med"},{"key":"2025012715573878500_llae210-B2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1136\/jmg.30.6.460","article-title":"Complications of the naevoid basal cell carcinoma syndrome: results of a population based study","volume":"30","author":"Evans","year":"1993","journal-title":"J Med Genet"},{"key":"2025012715573878500_llae210-B3","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1002\/(SICI)1096-8628(19970331)69:3<299::AID-AJMG16>3.0.CO;2-M","article-title":"Clinical manifestations in 105 persons with nevoid basal cell carcinoma syndrome","volume":"69","author":"Kimonis","year":"1997","journal-title":"Am J Med Genet"},{"key":"2025012715573878500_llae210-B4","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1126\/science.272.5268.1668","article-title":"Human homolog of patched, a candidate gene for the basal cell nevus syndrome","volume":"272","author":"Johnson","year":"1996","journal-title":"Science"},{"key":"2025012715573878500_llae210-B5","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1016\/S0092-8674(00)81268-4","article-title":"Mutations of the human homolog of drosophila patched in the nevoid basal cell carcinoma syndrome","volume":"85","author":"Hahn","year":"1996","journal-title":"Cell"},{"key":"2025012715573878500_llae210-B6","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/0092-8674(92)90122-S","article-title":"Developmental defects in Gorlin syndrome related to a putative tumor suppressor gene on chromosome 9","volume":"69","author":"Gailani","year":"1992","journal-title":"Cell"},{"key":"2025012715573878500_llae210-B7","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1007\/s10689-012-9548-0","article-title":"Two cases of nevoid basal cell carcinoma syndrome associated with meningioma caused by a PTCH1 or SUFU germline mutation","volume":"11","author":"Kijima","year":"2012","journal-title":"Fam Cancer"},{"key":"2025012715573878500_llae210-B8","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1200\/JCO.2014.58.2569","article-title":"Germline mutations in SUFU cause Gorlin syndrome-associated childhood medulloblastoma and redefine the risk associated with PTCH1 mutations","volume":"32","author":"Smith","year":"2014","journal-title":"J\u00a0Clin Oncol"},{"key":"2025012715573878500_llae210-B9","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1136\/jmg.2007.055343","article-title":"A missense mutation in PTCH2 underlies dominantly inherited NBCCS in a Chinese family","volume":"45","author":"Fan","year":"2008","journal-title":"J Med Genet"},{"key":"2025012715573878500_llae210-B10","doi-asserted-by":"crossref","first-page":"103842","DOI":"10.1016\/j.ejmg.2020.103842","article-title":"Gorlin-like phenotype in a patient with a PTCH2 variant of uncertain significance","volume":"63","author":"Casano","year":"2020","journal-title":"Eur J Med Genet"},{"key":"2025012715573878500_llae210-B11","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1007\/s10689-013-9623-1","article-title":"Frameshift mutation in the PTCH2 gene can cause nevoid basal cell carcinoma syndrome","volume":"12","author":"Fujii","year":"2013","journal-title":"Fam Cancer"},{"key":"2025012715573878500_llae210-B12","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s10689-021-00269-7","article-title":"PTCH2 is not a strong candidate gene for Gorlin syndrome predisposition","volume":"21","author":"Smith","year":"2022","journal-title":"Fam Cancer"},{"key":"2025012715573878500_llae210-B13","doi-asserted-by":"crossref","first-page":"217378","DOI":"10.1155\/2011\/217378","article-title":"Basal cell carcinomas in Gorlin syndrome: a review of 202 patients","volume":"2011","author":"Jones","year":"2011","journal-title":"J Skin Cancer"},{"key":"2025012715573878500_llae210-B14","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1136\/jmedgenet-2017-104669","article-title":"First evidence of genotype\u2013phenotype correlations in Gorlin syndrome","volume":"54","author":"Evans","year":"2017","journal-title":"J Med Genet"},{"key":"2025012715573878500_llae210-B15","article-title":"Gorlin syndrome","author":"OrphaNet"},{"key":"2025012715573878500_llae210-B16","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/bjd.20700","article-title":"A guideline for the clinical management of basal cell naevus syndrome (Gorlin\u2013Goltz syndrome)","volume":"186","author":"Verkouteren","year":"2022","journal-title":"Br J Dermatol"},{"key":"2025012715573878500_llae210-B17","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res"},{"key":"2025012715573878500_llae210-B18","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"2025012715573878500_llae210-B19","doi-asserted-by":"crossref","first-page":"l1","DOI":"10.1126\/scisignal.2004088","article-title":"Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal","volume":"6","author":"Gao","year":"2013","journal-title":"Sci Signal"},{"key":"2025012715573878500_llae210-B20","doi-asserted-by":"crossref","first-page":"D1062","DOI":"10.1093\/nar\/gkx1153","article-title":"ClinVar: improving access to variant interpretations and supporting evidence","volume":"46","author":"Landrum","year":"2018","journal-title":"Nucleic Acids Res"},{"key":"2025012715573878500_llae210-B21","doi-asserted-by":"crossref","first-page":"1796","DOI":"10.1038\/s41431-021-00959-x","article-title":"The LOVD3 platform: efficient genome-wide sharing of genetic variants","volume":"29","author":"Fokkema","year":"2021","journal-title":"Eur J Hum Genet"},{"key":"2025012715573878500_llae210-B22","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1002\/humu.10212","article-title":"The Human Gene Mutation Database (HGMD): 2003 update","volume":"21","author":"Stenson","year":"2003","journal-title":"Hum Mutat"},{"key":"2025012715573878500_llae210-B23","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1038\/s41431-020-00755-z","article-title":"MobiDetails: online DNA variants interpretation","volume":"29","author":"Baux","year":"2021","journal-title":"Eur J Hum Genet"},{"key":"2025012715573878500_llae210-B24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"}],"container-title":["Clinical and Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ced\/advance-article-pdf\/doi\/10.1093\/ced\/llae210\/60749660\/llae210.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ced\/article-pdf\/50\/2\/380\/60749660\/llae210.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ced\/article-pdf\/50\/2\/380\/60749660\/llae210.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T15:58:14Z","timestamp":1737993494000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ced\/article\/50\/2\/380\/7676696"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,20]]},"references-count":24,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,5,20]]},"published-print":{"date-parts":[[2025,1,27]]}},"URL":"https:\/\/doi.org\/10.1093\/ced\/llae210","relation":{},"ISSN":["0307-6938","1365-2230"],"issn-type":[{"value":"0307-6938","type":"print"},{"value":"1365-2230","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,2]]},"published":{"date-parts":[[2024,5,20]]}}}