{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T15:02:28Z","timestamp":1785078148629,"version":"3.55.0"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004241","name":"China Primary Health Care Foundation","doi-asserted-by":"publisher","award":["BH005417"],"award-info":[{"award-number":["BH005417"]}],"id":[{"id":"10.13039\/501100004241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by resistance to adrenocorticotropic hormone (ACTH), leading to isolated glucocorticoid deficiency. This study aims to identify the genetic basis of FGD in a Chinese patient and investigate the functional consequences of the detected\n                      <jats:italic>MC2R<\/jats:italic>\n                      mutations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole\u2010exome sequencing was performed to detect pathogenic variants in the\n                      <jats:italic>MC2R<\/jats:italic>\n                      gene. The effects of these mutations on\n                      <jats:italic>MC2R<\/jats:italic>\n                      mRNA and protein levels were analyzed using qPCR and immunoblotting. Additionally, a luciferase reporter assay was conducted to evaluate ACTH\u2010induced cyclic adenosine monophosphate (cAMP) signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The patient was found to carry compound heterozygous mutations in\n                      <jats:italic>MC2R<\/jats:italic>\n                      (p.Leu151Pro and p.Glu28*), inherited from the father and mother, respectively. Functional studies revealed that these mutations led to reduced\n                      <jats:italic>MC2R<\/jats:italic>\n                      mRNA and protein expression. Furthermore, the luciferase assay demonstrated that these variants attenuated ACTH\u2010induced cAMP signaling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Novel pathogenic mutations in the\n                      <jats:italic>MC2R<\/jats:italic>\n                      gene were identified, and their functional impact was characterized. These findings provide insights into the molecular mechanisms underlying FGD and contribute to the expanding genetic spectrum of the disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70242","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T04:36:44Z","timestamp":1784176604000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Mutations in the\n                    <i>MC2R<\/i>\n                    Gene in a Patient With Familial Glucocorticoid Deficiency (\n                    <scp>FGD<\/scp>\n                    ): A Case Report and Functional Study"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7009-110X","authenticated-orcid":false,"given":"Ni","family":"Zhen","sequence":"first","affiliation":[{"name":"Department of Pediatrics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"},{"name":"Department of Endocrine and Metabolism Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9493-9198","authenticated-orcid":false,"given":"Yonghui","family":"Tao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Molecular Biology, Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8007-6878","authenticated-orcid":false,"given":"Chuanyin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery and Oncology The Second Affiliated Hospital, Zhejiang University School of Medicine  Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5027-8372","authenticated-orcid":false,"given":"Wenli","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1159\/000323913"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020\u2010026\u201004557\u2010z"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000526320"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102265.2000.01122.x"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2004.03.015"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.15.9033"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018\u201000386"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2190508"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000533986"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102265.2006.02709.x"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.34763\/devperiodmed.20182203.280283"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvac058"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejendo\/lvaf152"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/ec\u201019\u20100190"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.37"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1515\/jpem\u20102021\u20100150"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2016.00024"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399\u20100004.1998.531530112.x"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2017.62"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1499"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2017.132"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06729"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912176107"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2024.103368"}],"container-title":["Molecular Genetics &amp; 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