{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:49:17Z","timestamp":1747198157281,"version":"3.40.5"},"reference-count":11,"publisher":"Walter de Gruyter GmbH","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2023-0533_abs_402\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Inactivating <jats:italic>GNAS<\/jats:italic> mutations result in varied phenotypes depending on parental origin. Maternally inherited mutations typically lead to hormone resistance and Albright's hereditary osteodystrophy (AHO), characterised by short stature, round facies, brachydactyly and subcutaneous ossifications. Paternal inheritance presents with features of AHO or ectopic ossification without hormone resistance. This report describes the case of a child with osteoma cutis and medulloblastoma. The objective of this report is to highlight the emerging association between inactivating germline <jats:italic>GNAS<\/jats:italic> mutations and medulloblastoma, aiming to shed light on its implications for tumor biology and promote future development of targeted surveillance strategies to improve outcomes in paediatric patients with these mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2023-0533_abs_302\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>A 12-month-old boy presented with multiple plaque-like skin lesions. Biopsy confirmed osteoma cutis, prompting genetic testing which confirmed a heterozygous inactivating <jats:italic>GNAS<\/jats:italic> mutation. At 2.5 years of age, he developed neurological symptoms and was diagnosed with a desmoplastic nodular medulloblastoma, SHH molecular group, confirmed by MRI and histology. Further analysis indicated a biallelic loss of <jats:italic>GNAS <\/jats:italic>in the tumor.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2023-0533_abs_102\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This case provides important insights into the role of <jats:italic>GNAS<\/jats:italic> as a tumor suppressor and the emerging association between inactivating <jats:italic>GNAS<\/jats:italic> variants and the development of medulloblastoma. The case underscores the importance of careful neurological assessment and ongoing vigilance in children with known inactivating <jats:italic>GNAS<\/jats:italic> variants or associated phenotypes. Further work to establish genotype\u2013phenotype correlations is needed to inform optimal management of these patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2023-0533","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T10:42:05Z","timestamp":1711449725000},"page":"467-471","source":"Crossref","is-referenced-by-count":0,"title":["Medulloblastoma in a child with osteoma cutis\u00a0\u2013 a rare association due to loss of <i>GNAS<\/i> expression"],"prefix":"10.1515","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7158-999X","authenticated-orcid":false,"given":"Jananie","family":"Suntharesan","sequence":"first","affiliation":[{"name":"Department of Endocrinology , Alder Hey Children\u2019s Hospital , Liverpool , UK"},{"name":"Department of Paediatric and Adolocents Diabetes and Endocrinology, Sirimavo Bandaranayake Specialized Children\u2019s Hospital , Peradeniya , Sri Lanka"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2472-5829","authenticated-orcid":false,"given":"Ekaterina","family":"Lyulcheva-Bennett","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Genomic Medicine (LCGM) , Liverpool Women\u2019s NHS Foundation Trust , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel","family":"Hart","sequence":"additional","affiliation":[{"name":"Liverpool Centre for Genomic Medicine (LCGM) , Liverpool Women\u2019s NHS Foundation Trust , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Pizer","sequence":"additional","affiliation":[{"name":"Department of Oncology , Alder Hey Children\u2019s Hospital , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"Hayden","sequence":"additional","affiliation":[{"name":"Department of Oncology , Alder Hey Children\u2019s Hospital , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renuka","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology , Alder Hey Children\u2019s Hospital , Liverpool , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2024,3,27]]},"reference":[{"key":"2024081908520424767_j_jpem-2023-0533_ref_001","doi-asserted-by":"crossref","unstructured":"Mantovani, G, Spada, A, Elli, FM. Pseudohypoparathyroidism and Gs\u03b1\u2013cAMP-linked disorders: current view and open issues. Nat Rev Endocrinol 2016;12:347\u201356. https:\/\/doi.org\/10.1038\/nrendo.2016.52.","DOI":"10.1038\/nrendo.2016.52"},{"key":"2024081908520424767_j_jpem-2023-0533_ref_002","doi-asserted-by":"crossref","unstructured":"Weinstein, LS, Chen, M, Liu, J. Gs(alpha) mutations and imprinting defects in human disease. Ann N. Y Acad Sci 2002;968:173\u201397. https:\/\/doi.org\/10.1111\/j.1749-6632.2002.tb04335.x.","DOI":"10.1111\/j.1749-6632.2002.tb04335.x"},{"key":"2024081908520424767_j_jpem-2023-0533_ref_003","doi-asserted-by":"crossref","unstructured":"Tafaj, O, J\u00fcppner, H. Pseudohypoparathyroidism: one gene, several syndromes. J Endocrinol Invest 2017;40:347\u201356. https:\/\/doi.org\/10.1007\/s40618-016-0588-4.","DOI":"10.1007\/s40618-016-0588-4"},{"key":"2024081908520424767_j_jpem-2023-0533_ref_004","unstructured":"Haldeman-Englert, CR, Hurst, AC, Levine, MA. 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JCO Precis Oncol 2022;6:e2100403. https:\/\/doi.org\/10.1200\/po.21.00403.","DOI":"10.1200\/PO.21.00403"},{"key":"2024081908520424767_j_jpem-2023-0533_ref_009","doi-asserted-by":"crossref","unstructured":"Crane, JN, Chang, VY, Yong, WH, Salamon, N, Hane Lee for UCLA\u00a0Clinical\u00a0Genomics Center, Kianmahd, J, et al.. A case report\u00a0of\u00a0a\u00a0novel germline GNAS mutation in sonic hedgehog\u00a0activated\u00a0medulloblastoma. Pediatr Blood Cancer 2020;67:e28103. https:\/\/doi.org\/10.1002\/pbc.28103.","DOI":"10.1002\/pbc.28103"},{"key":"2024081908520424767_j_jpem-2023-0533_ref_010","doi-asserted-by":"crossref","unstructured":"Tokita, MJ, Nahas, S, Briggs, B, Malicki, DM, Mesirov, JP, Reyes, IAC, et al.. Biallelic loss of GNAS in a patient with pediatric medulloblastoma. Cold Spring Harb Mol Case Stud 2019;5:a004572. https:\/\/doi.org\/10.1101\/mcs.a004572.","DOI":"10.1101\/mcs.a004572"},{"key":"2024081908520424767_j_jpem-2023-0533_ref_011","doi-asserted-by":"crossref","unstructured":"Huh, JY, Kwon, MJ, Seo, KY, Kim, MK, Chae, KY, Kim, SH, et al.. Novel\u00a0nonsense GNAS mutation in a 14-month-old boy with plate-like osteoma cutis and medulloblastoma. 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