{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:18:41Z","timestamp":1791944321736,"version":"4.3.4"},"reference-count":30,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T00:00:00Z","timestamp":1586908800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2016YFC0905100"],"award-info":[{"award-number":["2016YFC0905100"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAMS Innovation Fund for Medical Sciences","award":["2016-I2M-1\u2013002"],"award-info":[{"award-number":["2016-I2M-1\u2013002"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971375"],"award-info":[{"award-number":["81971375"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>Defects in both CYP21A2 and TNXB genes can cause congenital adrenal hyperplasia combined with hypermobility-type Ehlers\u2013Danlos syndrome (EDS), which has recently been named CAH-X syndrome. The purpose of this study is to assess the prevalence of the chimeric TNXA\/TNXB gene and clinical symptoms in a Chinese cohort with 21-hydroxylase deficiency (21-OHD).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 424 patients with 21-OHD who were genetically diagnosed were recruited for this study. Multiplex ligation-dependent probe amplification and sequencing were used to identify the CAH-X genotype. Clinical features of joints, skin, and other systems were evaluated in 125 patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Ninety-four of the 424 patients had a deletion on at least 1 allele of CYP21A2 and 59 of them harbored the heterozygotic TNXA\/TNXB chimera. Frequencies of CAH-X CH-1, CH-2, and CH-3 were 8.2%, 3.1%, and 2.6%, respectively. The incidences of clinical features of EDS were 71.0% and 26.6% in patients with the chimeric TNXA\/TNXB genes or without (P &amp;lt; .001). There were statistically significant differences in manifestations among articular (P &amp;lt; .001 in generalized hypermobility) and dermatologic features (P &amp;lt; .001 in hyperextensible skin, P = .015 in velvety skin and P = .033 in poor wound healing). The prevalence of generalized hypermobility was more common in CAH-X CH-2 or CH-3 than CH-1 patients (60% vs 20%, P = .028).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>In summary, about 14% of patients with 21-OHD may have chimeric TNXA\/TNXB gene mutations in our study and most of them showed EDS-related clinical symptoms. The correlation between CAH-X genotypes and clinical features in connective tissue, like joint or skin, needs to be further investigated.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa199","type":"journal-article","created":{"date-parts":[[2020,4,15]],"date-time":"2020-04-15T03:05:45Z","timestamp":1586919945000},"page":"2288-2299","source":"Crossref","is-referenced-by-count":32,"title":["The Prevalence of the Chimeric <i>TNXA\/TNXB<\/i> Gene and Clinical Symptoms of Ehlers\u2013Danlos Syndrome with 21-Hydroxylase Deficiency"],"prefix":"10.1210","volume":"105","author":[{"given":"Yinjie","family":"Gao","sequence":"first","affiliation":[{"name":"NHC key laboratory of Endocrinology, Peking Union Medical College Hospital; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Lu","sequence":"additional","affiliation":[{"name":"NHC key laboratory of Endocrinology, Peking Union Medical College Hospital; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingqing","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0157-1545","authenticated-orcid":false,"given":"Jiangfeng","family":"Mao","sequence":"additional","affiliation":[{"name":"NHC key laboratory of Endocrinology, Peking Union Medical College Hospital; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"NHC key laboratory of Endocrinology, Peking Union Medical College Hospital; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-0044","authenticated-orcid":false,"given":"Min","family":"Nie","sequence":"additional","affiliation":[{"name":"NHC key laboratory of Endocrinology, Peking Union Medical College Hospital; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyan","family":"Wu","sequence":"additional","affiliation":[{"name":"NHC key laboratory of Endocrinology, Peking Union Medical College Hospital; Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2020,4,15]]},"reference":[{"issue":"10108","key":"2021122116304285200_CIT0001","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1016\/S0140-6736(17)31431-9","article-title":"Congenital adrenal hyperplasia","volume":"390","author":"El-Maouche","year":"2017","journal-title":"Lancet."},{"issue":"11","key":"2021122116304285200_CIT0002","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1210\/jc.2018-01865","article-title":"Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society Clinical Practice Guideline","volume":"103","author":"Speiser","year":"2018","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2021122116304285200_CIT0003","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jpeds.2013.02.008","article-title":"Optimizing newborn screening for congenital adrenal hyperplasia","volume":"163","author":"White","year":"2013","journal-title":"J Pediatr."},{"issue":"5","key":"2021122116304285200_CIT0004","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1111\/cen.13429","article-title":"Pregnancy in women with nonclassic congenital adrenal hyperplasia: Time to conceive and outcome","volume":"87","author":"Eyal","year":"2017","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"3","key":"2021122116304285200_CIT0005","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1515\/jpem-2018-0342","article-title":"A pilot study on newborn screening for congenital adrenal hyperplasia in Beijing","volume":"32","author":"Gong","year":"2019","journal-title":"J Pediatr Endocrinol Metab."},{"issue":"1","key":"2021122116304285200_CIT0006","first-page":"16","article-title":"[Neonatal screening for congenital adrenal hyperplasia in Shanghai areas]","volume":"36","author":"Gu","year":"2002","journal-title":"Zhonghua Yu Fang Yi Xue Za Zhi."},{"issue":"5","key":"2021122116304285200_CIT0007","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/j.ygeno.2003.11.006","article-title":"PCR-based detection of the CYP21 deletion and TNXA\/TNXB hybrid in the RCCX module","volume":"83","author":"Lee","year":"2004","journal-title":"Genomics."},{"issue":"17","key":"2021122116304285200_CIT0008","doi-asserted-by":"crossref","first-page":"12147","DOI":"10.1074\/jbc.274.17.12147","article-title":"Modular variations of the human major histocompatibility complex class III genes for serine\/threonine kinase RP, complement component C4, steroid 21-hydroxylase CYP21, and tenascin TNX (the RCCX module). A mechanism for gene deletions and disease associations","volume":"274","author":"Yang","year":"1999","journal-title":"J Biol Chem."},{"issue":"1","key":"2021122116304285200_CIT0009","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1093\/gbe\/evs121","article-title":"Intraspecific evolution of human RCCX copy number variation traced by haplotypes of the CYP21A2 gene","volume":"5","author":"B\u00e1nlaki","year":"2013","journal-title":"Genome Biol Evol."},{"issue":"1","key":"2021122116304285200_CIT0010","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ymgme.2004.09.009","article-title":"Chimeric CYP21P\/CYP21 and TNXA\/TNXB genes in the RCCX module","volume":"84","author":"Lee","year":"2005","journal-title":"Mol Genet Metab."},{"issue":"2","key":"2021122116304285200_CIT0011","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s10038-003-0115-2","article-title":"The chimeric CYP21P\/CYP21 gene and 21-hydroxylase deficiency","volume":"49","author":"Lee","year":"2004","journal-title":"J Hum Genet."},{"issue":"2","key":"2021122116304285200_CIT0012","doi-asserted-by":"crossref","first-page":"17","DOI":"10.5496\/wjmg.v6.i2.17","article-title":"Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome","volume":"6","author":"Kaufman","year":"2016","journal-title":"World J Med Genet."},{"issue":"1","key":"2021122116304285200_CIT0013","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1399-0004.2012.01858.x","article-title":"The Ehlers-Danlos syndrome, a disorder with many faces","volume":"82","author":"De Paepe","year":"2012","journal-title":"Clin Genet."},{"issue":"3","key":"2021122116304285200_CIT0014","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1111\/cge.12853","article-title":"Recognizing the tenascin-X deficient type of Ehlers-Danlos syndrome: a cross-sectional study in 17 patients","volume":"91","author":"Demirdas","year":"2017","journal-title":"Clin Genet."},{"issue":"4","key":"2021122116304285200_CIT0015","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1002\/ajmg.a.37547","article-title":"An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing","volume":"170A","author":"Mackenroth","year":"2016","journal-title":"Am J Med Genet A."},{"issue":"17","key":"2021122116304285200_CIT0016","first-page":"V01160014","article-title":"[Ehlers-Danlos syndrome]","volume":"178","author":"Leganger","year":"2016","journal-title":"Ugeskr Laeger"},{"issue":"1","key":"2021122116304285200_CIT0017","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1086\/376564","article-title":"Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome","volume":"73","author":"Zweers","year":"2003","journal-title":"Am J Hum Genet."},{"issue":"16","key":"2021122116304285200_CIT0018","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1056\/NEJMoa002939","article-title":"A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency","volume":"345","author":"Schalkwijk","year":"2001","journal-title":"N Engl J Med."},{"issue":"2","key":"2021122116304285200_CIT0019","doi-asserted-by":"crossref","first-page":"E379","DOI":"10.1210\/jc.2012-3148","article-title":"Tenascin-X haploinsufficiency associated with Ehlers-Danlos syndrome in patients with congenital adrenal hyperplasia","volume":"98","author":"Merke","year":"2013","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122116304285200_CIT0020","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1159\/000481911","article-title":"Tenascin-X, congenital adrenal hyperplasia, and the CAH-X syndrome","volume":"89","author":"Miller","year":"2018","journal-title":"Horm Res Paediatr."},{"issue":"8","key":"2021122116304285200_CIT0021","doi-asserted-by":"crossref","first-page":"E1143","DOI":"10.1210\/jc.2015-2232","article-title":"Broadening the spectrum of Ehlers Danlos syndrome in patients with congenital adrenal hyperplasia","volume":"100","author":"Morissette","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"9","key":"2021122116304285200_CIT0022","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1002\/humu.23028","article-title":"Ehlers-Danlos syndrome caused by biallelic TNXB variants in patients with congenital adrenal hyperplasia","volume":"37","author":"Chen","year":"2016","journal-title":"Hum Mutat."},{"issue":"1","key":"2021122116304285200_CIT0023","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/ajmg.c.31538","article-title":"Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): clinical description and natural history","volume":"175","author":"Tinkle","year":"2017","journal-title":"Am J Med Genet C Semin Med Genet."},{"issue":"5","key":"2021122116304285200_CIT0024","doi-asserted-by":"crossref","first-page":"924","DOI":"10.1016\/j.jmoldx.2019.06.001","article-title":"High-throughput screening for CYP21A1P-TNXA\/TNXB chimeric genes responsible for Ehlers-Danlos syndrome in patients with congenital adrenal hyperplasia","volume":"21","author":"Lao","year":"2019","journal-title":"J Mol Diagn."},{"key":"2021122116304285200_CIT0025","article-title":"The prevalence of heterozygous CYP21A2 deficiency in patients with idiopathic acne, hirsutism, or both","author":"Gao","year":"2019","journal-title":"Endocrine"},{"issue":"5","key":"2021122116304285200_CIT0026","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1136\/ard.32.5.413","article-title":"Articular mobility in an African population","volume":"32","author":"Beighton","year":"1973","journal-title":"Ann Rheum Dis."},{"issue":"11","key":"2021122116304285200_CIT0027","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1093\/rheumatology\/kex043","article-title":"Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population","volume":"56","author":"Singh","year":"2017","journal-title":"Rheumatology (Oxford)."},{"issue":"2-3","key":"2021122116304285200_CIT0028","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.ejmg.2013.12.004","article-title":"Transforming growth factor-\u03b2 (TGF-\u03b2) pathway abnormalities in tenascin-X deficiency associated with CAH-X syndrome","volume":"57","author":"Morissette","year":"2014","journal-title":"Eur J Med Genet."},{"key":"2021122116304285200_CIT0029","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.steroids.2016.01.007","article-title":"21-hydroxylase deficiency-induced congenital adrenal hyperplasia in 230 Chinese patients: genotype-phenotype correlation and identification of nine novel mutations","volume":"108","author":"Wang","year":"2016","journal-title":"Steroids."},{"issue":"9","key":"2021122116304285200_CIT0030","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1248\/bpb.b19-00168","article-title":"Measurement of serum Tenascin-X in joint hypermobility syndrome patients","volume":"42","author":"Yamada","year":"2019","journal-title":"Biol Pharm Bull."}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgaa199\/33045468\/dgaa199.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/7\/2288\/41839873\/jcem_105_7_2288.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/article-pdf\/105\/7\/2288\/41839873\/jcem_105_7_2288.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T16:37:44Z","timestamp":1640104664000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/105\/7\/2288\/5820120"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,15]]},"references-count":30,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,4,15]]},"published-print":{"date-parts":[[2020,7,1]]}},"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgaa199","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,7]]},"published":{"date-parts":[[2020,4,15]]}}}