{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T05:12:24Z","timestamp":1783746744481,"version":"3.55.0"},"reference-count":24,"publisher":"Japanese Society for Pediatric Endocrinology","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pediatr Endocrinol"],"published-print":{"date-parts":[[2026]]},"DOI":"10.1297\/cpe.2025-0081","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T22:08:36Z","timestamp":1774735716000},"page":"272-278","source":"Crossref","is-referenced-by-count":0,"title":["Severe infantile obesity with a maternal &lt;i&gt;GNAS&lt;\/i&gt; deletion and multi-locus imprinting disturbance including hypomethylation of the &lt;i&gt;KCNQ1OT1&lt;\/i&gt;:TSS-DMR"],"prefix":"10.1297","volume":"35","author":[{"given":"Tatsuki","family":"Urakawa","sequence":"first","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"},{"name":"Department of Pediatrics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaharu","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinichiro","family":"Sano","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Metabolism, Shizuoka Children\u2019s Hospital, Shizuoka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Ohtsu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maki","family":"Fukami","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayo","family":"Kagami","sequence":"additional","affiliation":[{"name":"Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"125","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Monk, D, Mackay, DJG, Eggermann, T, Maher, ER, Riccio, A. Genomic imprinting disorders: lessons on how genome, epigenome and environment interact. Nat Rev Genet 2019;20: 235\u201348.","DOI":"10.1038\/s41576-018-0092-0"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Eggermann, T, Monk, D, de Nanclares, GP, Kagami, M, Giabicani, E, Riccio, A, et al. Imprinting disorders. Nat Rev Dis Primers 2023;9: 33.","DOI":"10.1038\/s41572-023-00443-4"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Iwasaki, Y, Bastepe, M. Imprinting and skeletal disorders: lessons from pseudohypoparathyroidism and related disorders. J Bone Miner Res 2025;40: 1207\u201317.","DOI":"10.1093\/jbmr\/zjaf122"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Mantovani, G, Bastepe, M, Monk, D, de Sanctis, L, Thiele, S, Usardi, A, et al. Diagnosis and management of pseudohypoparathyroidism and related disorders: first international Consensus Statement. Nat Rev Endocrinol 2018;14: 476\u2013500.","DOI":"10.1038\/s41574-018-0042-0"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. Mantovani, G, Bondioni, S, Locatelli, M, Pedroni, C, Lania, AG, Ferrante, E, et al. Biallelic expression of the Gsalpha gene in human bone and adipose tissue. J Clin Endocrinol Metab 2004;89: 6316\u20139.","DOI":"10.1210\/jc.2004-0558"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Fei, Y, Liu, L, Wu, L, Wang, O, Xing, X, Li, A, et al. Whole-genome sequencing revealed a novel long-range deletion mutation spanning GNAS in familial pseudohypoparathyroidism. Mol Genet Genomic Med 2023;11: e2144.","DOI":"10.1002\/mgg3.2144"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Sano, S, Nakamura, A, Matsubara, K, Nagasaki, K, Fukami, M, Kagami, M, et al. (Epi)genotype-Phenotype Analysis in 69 Japanese Patients With Pseudohypoparathyroidism Type I. J Endocr Soc 2017;2: 9\u201323.","DOI":"10.1210\/js.2017-00293"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8. Hanna, P, Grybek, V, Perez de Nanclares, G, Tran, LC, de Sanctis, L, Elli, F, et al. Genetic and epigenetic defects at the GNAS locus lead to distinct patterns of skeletal growth but similar early-onset obesity. J Bone Miner Res 2018;33: 1480\u20138.","DOI":"10.1002\/jbmr.3450"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Urakawa, T, Sano, S, Kawashima, S, Nakamura, A, Shima, H, Ohta, M, et al. (Epi)genetic and clinical characteristics in 84 patients with pseudohypoparathyroidism type 1B. Eur J Endocrinol 2023;189: 590\u2013600.","DOI":"10.1093\/ejendo\/lvad163"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Mantovani, G, Bastepe, M, Monk, D, de Sanctis, L, Thiele, S, Ahmed, SF, et al. Recommendations for diagnosis and treatment of pseudohypoparathyroidism and related disorders: an updated practical tool for physicians and patients. Horm Res Paediatr 2020;93: 182\u201396.","DOI":"10.1159\/000508985"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Brioude, F, Kalish, JM, Mussa, A, Foster, AC, Bliek, J, Ferrero, GB, et al. Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement. Nat Rev Endocrinol 2018;14: 229\u201349.","DOI":"10.1038\/nrendo.2017.166"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Mackay, DJG, Gazdagh, G, Monk, D, Brioude, F, Giabicani, E, Krzyzewska, IM, et al. Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis. Clin Epigenetics 2024;16: 99.","DOI":"10.1186\/s13148-024-01713-y"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Urakawa, T, Soejima, H, Yamoto, K, Hara-Isono, K, Nakamura, A, Kawashima, S, et al. Comprehensive molecular and clinical findings in 29 patients with multi-locus imprinting disturbance. Clin Epigenetics 2024;16: 138.","DOI":"10.1186\/s13148-024-01744-5"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Monk, D, Sanchez-Delgado, M, Fisher, R. NLRPs, the subcortical maternal complex and genomic imprinting. Reproduction 2017;154: R161\u201370.","DOI":"10.1530\/REP-17-0465"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Nguyen, NMP, Khawajkie, Y, Mechtouf, N, Rezaei, M, Breguet, M, Kurvinen, E, et al. The genetics of recurrent hydatidiform moles: new insights and lessons from a comprehensive analysis of 113 patients. Mod Pathol 2018;31: 1116\u201330.","DOI":"10.1038\/s41379-018-0031-9"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Rong, Y, Wu, YK, Chen, Y, Liu, Q, Ai, L, Wu, YW, et al. ZAR1\/2-regulated epigenetic modifications are essential for age-associated oocyte quality maintenance and zygotic activation. Adv Sci (Weinh) 2025;12: e2410305.","DOI":"10.1002\/advs.202410305"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Ke, H, Tang, S, Guo, T, Hou, D, Jiao, X, Li, S, et al. Landscape of pathogenic mutations in premature ovarian insufficiency. Nat Med 2023;29: 483\u201392.","DOI":"10.1038\/s41591-022-02194-3"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Begemann, M, Rezwan, FI, Beygo, J, Docherty, LE, Kolarova, J, Schroeder, C, et al. Maternal variants in <i>NLRP<\/i> and other maternal effect proteins are associated with multilocus imprinting disturbance in offspring. J Med Genet 2018;55: 497\u2013504.","DOI":"10.1136\/jmedgenet-2017-105190"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Urakawa, T, Kanamaru, Y, Amano, N, Uchida, A, Fukami, M, Kagami, M. Multi-locus methylation analyses reveal GNAS methylation defects in three patients with the Beckwith-Wiedemann syndrome phenotype and no molecular defects in the 11p15.5 imprinted region. Clin Epigenetics 2025;17: 97.","DOI":"10.1186\/s13148-025-01907-y"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Richards, S, Aziz, N, Bale, S, Bick, D, Das, S, Gastier-Foster, J, et al. ACMG Laboratory Quality Assurance Committee. 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. Genet Med 2015;17: 405\u201324.","DOI":"10.1038\/gim.2015.30"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Hanna, P, Grybek, V, Perez de Nanclares, G, Tran, LC, de Sanctis, L, Elli, F, et al. Genetic and epigenetic defects at the GNAS locus lead to distinct patterns of skeletal growth but similar early-onset obesity. J Bone Miner Res 2018;33: 1480\u20138.","DOI":"10.1002\/jbmr.3450"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Maas, SM, Lauffer, P, Cocchi, G, DeMarchis, M, George, AM, Mussa, A, et al. Growth charts for children with Beckwith-Wiedemann spectrum. Am J Med Genet A 2025;197: e64073.","DOI":"10.1002\/ajmg.a.64073"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Borgese, N, Iacomino, N, Colombo, SF, Navone, F. The link between VAPB loss of function and amyotrophic lateral sclerosis. Cells 2021;10: 1865.","DOI":"10.3390\/cells10081865"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Svensson, PJ, Von Tell, D, Molander, ML, Anvret, M, Nordenskj\u00f6ld, A. A heterozygous frameshift mutation in the endothelin-3 (EDN-3) gene in isolated Hirschsprung\u2019s disease. Pediatr Res 1999;45: 714\u20137.","DOI":"10.1203\/00006450-199905010-00018"}],"container-title":["Clinical Pediatric Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/35\/3\/35_2025-0081\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T04:23:59Z","timestamp":1783743839000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/cpe\/35\/3\/35_2025-0081\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1297\/cpe.2025-0081","relation":{},"ISSN":["0918-5739","1347-7358"],"issn-type":[{"value":"0918-5739","type":"print"},{"value":"1347-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026]]},"article-number":"2025-0081"}}