{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:28:40Z","timestamp":1782174520057,"version":"3.54.5"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T00:00:00Z","timestamp":1679616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Institute of health Research Biomedical Research centre Manchester","award":["IS-BRC-1215-20007"],"award-info":[{"award-number":["IS-BRC-1215-20007"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Familial Cancer"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Recent genetic sequencing studies in large series\u2019 of predominantly childhood medulloblastoma have implicated loss-of-function, predominantly truncating, variants in the\n                    <jats:italic>ELP1<\/jats:italic>\n                    and\n                    <jats:italic>GPR161<\/jats:italic>\n                    genes in causation of the MB\n                    <jats:sub>SHH<\/jats:sub>\n                    subtype specifically. The latter association, along with a report of an index case with some features of Gorlin syndrome has led to speculation that\n                    <jats:italic>GPR161<\/jats:italic>\n                    may also cause Gorlin syndrome. We show that these genes are associated with relatively low absolute risks of medulloblastoma from extrapolating lifetime risks in the general population and odds ratios from the population database gnomAD. The projected risks are around 1 in 270\u2013430 for\n                    <jats:italic>ELP1<\/jats:italic>\n                    and 1 in 1600\u20132500 for\n                    <jats:italic>GPR161.<\/jats:italic>\n                    These risks do not suggest the need for MRI screening in infants with\n                    <jats:italic>ELP1<\/jats:italic>\n                    or\n                    <jats:italic>GPR161<\/jats:italic>\n                    variants as this is not currently recommended for\n                    <jats:italic>PTCH1<\/jats:italic>\n                    where the risks are equivalent or higher. We also screened 27\n                    <jats:italic>PTCH1\/SUFU<\/jats:italic>\n                    pathogenic variant-negative patients with Gorlin syndrome for\n                    <jats:italic>GPR161<\/jats:italic>\n                    and found no suspicious variants. Given the population frequencies of 0.0962% for\n                    <jats:italic>GPR161<\/jats:italic>\n                    and 0.0687% for\n                    <jats:italic>ELP1<\/jats:italic>\n                    , neither of these genes can be a cause of Gorlin syndrome with an unexplained population frequency far lower at 0.0021%.\n                  <\/jats:p>","DOI":"10.1007\/s10689-023-00330-7","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T05:02:57Z","timestamp":1679634177000},"page":"341-344","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Perspectives on the implications of carrying putative pathogenic variants in the medulloblastoma predisposition genes ELP1 and GPR161"],"prefix":"10.1007","volume":"22","author":[{"given":"Miriam J","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma R","family":"Woodward","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-5784","authenticated-orcid":false,"given":"D Gareth","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,24]]},"reference":[{"key":"330_CR1","unstructured":"https:\/\/www.cancerresearchuk.org\/about-cancer\/childrens-cancer\/brain-tumours\/types\/medulloblastoma"},{"key":"330_CR2","unstructured":"https:\/\/www.cancer.net\/cancer-types\/medulloblastoma-childhood\/statistics#:~:text=About%2020%25%20of%20childhood%20brain,ages%20of%205%20and%209"},{"issue":"4","key":"330_CR3","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1007\/s10689-021-00247-z","volume":"20","author":"L Guerrini-Rousseau","year":"2021","unstructured":"Guerrini-Rousseau L, Smith MJ, Kratz CP et al (2021) Current recommendations for cancer surveillance in Gorlin syndrome: a report from the SIOPE host genome working group (SIOPE HGWG). Fam Cancer 20(4):317\u2013325. https:\/\/doi.org\/10.1007\/s10689-021-00247-z","journal-title":"Fam Cancer"},{"issue":"7803","key":"330_CR4","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1038\/s41586-020-2164-5","volume":"580","author":"SM Waszak","year":"2020","unstructured":"Waszak SM, Robinson GW, Gudenas BL et al (2020) Germline elongator mutations in Sonic hedgehog medulloblastoma. Nature 580(7803):396\u2013401. https:\/\/doi.org\/10.1038\/s41586-020-2164-5","journal-title":"Nature"},{"issue":"1","key":"330_CR5","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1200\/JCO.19.00577","volume":"38","author":"M Begemann","year":"2020","unstructured":"Begemann M, Waszak SM, Robinson GW et al (2020) Germline GPR161 mutations predispose to Pediatric Medulloblastoma. J Clin Oncol 38(1):43\u201350. https:\/\/doi.org\/10.1200\/JCO.19.00577Epub 2019 Oct 14","journal-title":"J Clin Oncol"},{"issue":"12","key":"330_CR6","doi-asserted-by":"publisher","first-page":"e62","DOI":"10.1158\/1078-0432.CCR-17-0595","volume":"23","author":"WD Foulkes","year":"2017","unstructured":"Foulkes WD, Kamihara J, Evans DGR et al (2017) Cancer Surveillance in Gorlin Syndrome and Rhabdoid Tumor Predisposition Syndrome. Clin Cancer Res 23(12):e62\u2013e67. https:\/\/doi.org\/10.1158\/1078-0432.CCR-17-0595","journal-title":"Clin Cancer Res"},{"issue":"2","key":"330_CR7","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/ajmg.a.33139","volume":"152A","author":"DG Evans","year":"2010","unstructured":"Evans DG, Howard E, Giblin C et al (2010) Birth incidence and prevalence of tumor-prone syndromes: estimates from a UK family genetic register service. Am J Med Genet A 152A(2):327\u2013332. https:\/\/doi.org\/10.1002\/ajmg.a.33139","journal-title":"Am J Med Genet A"},{"issue":"3","key":"330_CR8","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s10689-021-00269-7","volume":"21","author":"MJ Smith","year":"2022","unstructured":"Smith MJ, Evans DG (2022) PTCH2 is not a strong candidate gene for gorlin syndrome predisposition. Fam Cancer 21(3):343\u2013346. https:\/\/doi.org\/10.1007\/s10689-021-00269-7","journal-title":"Fam Cancer"},{"issue":"1","key":"330_CR9","doi-asserted-by":"publisher","first-page":"E140","DOI":"10.1210\/jc.2014-1984","volume":"100","author":"E Karaca","year":"2015","unstructured":"Karaca E, Buyukkaya R, Pehlivan D et al (2015) Whole-exome sequencing identifies homozygous GPR161 mutation in a family with pituitary stalk interruption syndrome. J Clin Endocrinol Metab 100(1):E140\u2013E147. https:\/\/doi.org\/10.1210\/jc.2014-1984","journal-title":"J Clin Endocrinol Metab"},{"key":"330_CR10","doi-asserted-by":"crossref","unstructured":"Guo Q, Yang Y, Mu Y et al (2013) : Pituitary stalk interruption syndrome in Chinese people: clinical characteristic analysis of 55 cases. PLoS One. 8: e53579-10.1371\/journal.pone.0053579","DOI":"10.1371\/journal.pone.0053579"}],"container-title":["Familial Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10689-023-00330-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10689-023-00330-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10689-023-00330-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T00:26:38Z","timestamp":1686875198000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10689-023-00330-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,24]]},"references-count":10,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["330"],"URL":"https:\/\/doi.org\/10.1007\/s10689-023-00330-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2300635\/v1","asserted-by":"object"}]},"ISSN":["1389-9600","1573-7292"],"issn-type":[{"value":"1389-9600","type":"print"},{"value":"1573-7292","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,24]]},"assertion":[{"value":"22 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 February 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors declare no conflict of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Ethical approval for the use of anonymised samples from the Manchester Centre for Genomic Medicine archive was obtained from the North West \u2013 Greater Manchester Central Research Ethics Committee (reference 10\/H1008\/74).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical declaration"}}]}}