{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T14:20:36Z","timestamp":1784557236887,"version":"3.55.0"},"reference-count":25,"publisher":"Bioscientifica","issue":"4","license":[{"start":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T00:00:00Z","timestamp":1677456000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,27]]},"abstract":"<jats:p>\n                    Pathogenic variants in the transcription factor CCCTC-binding factor (\n                    <jats:italic>CTCF<\/jats:italic>\n                    ) are associated with mental retardation, autosomal dominant 21 (MRD21, MIM#615502). Current studies supported the strong relationship between\n                    <jats:italic>CTCF<\/jats:italic>\n                    variants and growth, yet the mechanism of\n                    <jats:italic>CTCF<\/jats:italic>\n                    mutation leading to short stature is not known. Clinical information, treatment regimens, and follow-up outcomes of a patient with MRD21 were collected. The possible pathogenic mechanisms of\n                    <jats:italic>CTCF<\/jats:italic>\n                    variants leading to short stature were investigated using immortalized lymphocyte cell lines (LCLs), HEK-293T, and immortalized normal human liver cell lines (LO2). This patient received long-term treatment with recombinant human growth hormone (rhGH) which resulted in an increased height of 1.0 SDS. She had low serum insulin-like growth factor 1 (IGF1) before the treatment and the IGF1 level was not significantly increased during the treatment (\u22121.38 \u00b1 0.61 SDS). The finding suggested that the\n                    <jats:italic>CTCF<\/jats:italic>\n                    <jats:sup>R567W<\/jats:sup>\n                    variant could have impaired IGF1 production pathway. We further demonstrated that the mutant CTCF had a reduced ability to bind to the promoter region of IGF1, consequently significantly reducing the transcriptional activation and expression of IGF1. Our novel results demonstrated a direct positive regulation of CTCF on the transcription of the\n                    <jats:italic>IGF1<\/jats:italic>\n                    promoter. The impaired IGF1 expression due to CTCF mutation may explain the substandard effect of rhGH treatment on MRD21 patients. This study provided novel insights into the molecular basis of CTCF-associated disorder.\n                  <\/jats:p>","DOI":"10.1530\/jme-22-0193","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T05:45:32Z","timestamp":1677476732000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-6","source":"Crossref","is-referenced-by-count":2,"title":["CTCF variant begets to short stature by down-regulation of IGF1"],"prefix":"10.1530","volume":"70","author":[{"given":"Hong","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Fuzhou Children\u2019s Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Fuzhou Children\u2019s Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suping","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Fuzhou Children\u2019s Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunteng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Fuzhou Children\u2019s Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Genetic and Metabolic Central Laboratory, the Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Guangxi Birth Defects Prevention and Control Institute, Nanning, China"},{"name":"Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4114-7706","authenticated-orcid":true,"given":"Ruimin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Genetics and Metabolism, Fuzhou Children\u2019s Hospital of Fujian Medical University, Fuzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"American Journal of Medical Genetics. 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