{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T04:51:04Z","timestamp":1747198264128,"version":"3.40.5"},"reference-count":12,"publisher":"Walter de Gruyter GmbH","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,1,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2022-0396_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Congenital Adrenal Hyperplasia (CAH) is a group of genetic diseases characterized by impaired cortisol biosynthesis. 95% of CAH cases result from mutation in the CYP21A2 gene encoding 21-hydroxilase. TNX-B gene partially overlaps CYP21A2 and encodes a matrix protein called Tenascin-X (TNX). Complete tenascin deficiency causes Enlers-Danlos syndrome (EDS). A mono allelic variant called CAH-X CH-1 was recently described, resulting from a CYP21A2 complete deletion that extends into the TNXB. This haploinsufficiency of TNX may be associated with a mild hypermobility form of EDS, as well as other connective tissue comorbidities such as hernia, cardiac defects and chronic arthralgia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2022-0396_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>We report four patients heterozygous for a CAH-X CH-1 allele that do not present clinical manifestations of the EDS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2022-0396_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>All CAH patients, carriers of these TNXA\/TNXB chimeras, should be evaluated for clinical manifestations related to connective tissue hypermobility, cardiac abnormalities and other EDS features, allowing for better clinical surveillance management.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2022-0396","type":"journal-article","created":{"date-parts":[[2022,10,19]],"date-time":"2022-10-19T09:20:53Z","timestamp":1666171253000},"page":"81-85","source":"Crossref","is-referenced-by-count":1,"title":["Congenital adrenal hyperplasia with a <i>CYP21A2<\/i> deletion overlapping the tenascin-X gene: an atypical presentation"],"prefix":"10.1515","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3416-0446","authenticated-orcid":false,"given":"Catarina Rodrigues","family":"Ivo","sequence":"first","affiliation":[{"name":"Departamento de Endocrinologia , Hospital das For\u00e7as Armadas (HFAR) , Lisboa , Portugal"}]},{"given":"Ana Laura","family":"Fitas","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Pedi\u00e1trica , Hospital de Dona Estef\u00e2nia, Centro Hospitalar Universit\u00e1rio de Lisboa Central (CHULC) , Lisboa , Portugal"}]},{"given":"In\u00eas","family":"Madureira","sequence":"additional","affiliation":[{"name":"Unidade de Reumatologia Pedi\u00e1trica , Hospital de Dona Estef\u00e2nia, Centro Hospitalar Universit\u00e1rio de Lisboa Central (CHULC) , Lisboa , Portugal"}]},{"given":"Catarina","family":"Diamantino","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Pedi\u00e1trica , Hospital de Dona Estef\u00e2nia, Centro Hospitalar Universit\u00e1rio de Lisboa Central (CHULC) , Lisboa , Portugal"}]},{"given":"Susana","family":"Gomes","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana , Instituto Nacional de Sa\u00fade Dr. Ricardo Jorge , Lisboa , Portugal"}]},{"given":"Jo\u00e3o","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica Humana , Instituto Nacional de Sa\u00fade Dr. Ricardo Jorge , Lisboa , Portugal"}]},{"given":"Lurdes","family":"Lopes","sequence":"additional","affiliation":[{"name":"Unidade de Endocrinologia Pedi\u00e1trica , Hospital de Dona Estef\u00e2nia, Centro Hospitalar Universit\u00e1rio de Lisboa Central (CHULC) , Lisboa , Portugal"}]}],"member":"374","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"2023033122552034940_j_jpem-2022-0396_ref_001","doi-asserted-by":"crossref","unstructured":"Chen, W, Kim, MS, Shanbhag, S, Arai, A, VanRyzin, C, McDonnell, NB, et al.. The phenotypic spectrum of contiguous deletion of CYP21A2 and tenascin XB: quadricuspid aortic valve and other midline defects. Am J Med Genet Part A 2009;149A:2803\u20138.","DOI":"10.1002\/ajmg.a.33092"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_002","doi-asserted-by":"crossref","unstructured":"Miller, WL, Merke, DP. Tenascin-X, congenital adrenal hyperplasia, and the CAH-X syndrome. Horm Res Paediatr 2018;89:352\u201361. https:\/\/doi.org\/10.1159\/000481911.","DOI":"10.1159\/000481911"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_003","doi-asserted-by":"crossref","unstructured":"Lao, Q, Mallappa, A, Rueda Faucz, F, Joyal, E, Veeraraghavan, P, Chen, W, et al.. A TNXB splice donor site variant as a cause of hypermobility type Ehlers\u2013Danlos syndrome in patients with congenital adrenal hyperplasia. Mol Genet Genomic Med 2021;9:1\u20139. https:\/\/doi.org\/10.1002\/mgg3.1556.","DOI":"10.1002\/mgg3.1556"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_004","doi-asserted-by":"crossref","unstructured":"Merke, DP, Chen, W, Morissette, R, Xu, Z, Van Ryzin, C, Sachdev, V, et al.. Tenascin-X haploinsufficiency associated with ehlers-danlos syndrome in patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2013;98:1\u201317. https:\/\/doi.org\/10.1210\/jc.2012-3148.","DOI":"10.1210\/jc.2012-3148"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_005","doi-asserted-by":"crossref","unstructured":"Forghani, I. Updates in clinical and genetics aspects of hypermobile ehlers danlos syndrome. Balkan Med J 2019;26:12\u20136. https:\/\/doi.org\/10.4274\/balkanmedj.2018.1113.","DOI":"10.4274\/balkanmedj.2018.1113"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_006","doi-asserted-by":"crossref","unstructured":"Deodhar, AA, Woolf, AD. Ehlers Danlos syndrome and osteoporosis. 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Endocr Pract 2017;23:546\u201356. https:\/\/doi.org\/10.4158\/ep171751.or.","DOI":"10.4158\/EP171751.OR"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_009","doi-asserted-by":"crossref","unstructured":"Finkielstain, GP, Chen, W, Mehta, SP, Fujimura, FK, Hanna, RM, Van Ryzin, C, et al.. Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 2011;96:E161\u201372. https:\/\/doi.org\/10.1210\/jc.2010-0319.","DOI":"10.1210\/jc.2010-0319"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_010","doi-asserted-by":"crossref","unstructured":"Chen, W, Perritt, AF, Morissette, R, Dreiling, JL, Bohn, MF, Mallappa, A, et al.. Ehlers-Danlos syndrome caused by biallelic TNXB variants in patients with congenital adrenal hyperplasia. Hum Mutat 2016;37:893\u20137.","DOI":"10.1002\/humu.23028"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_011","doi-asserted-by":"crossref","unstructured":"Morissette, R, Chen, W, Perritt, AF, Dreiling, JL, Arai, AE, Sachdev, V, et al.. Broadening the spectrum of ehlers danlos syndrome in patients with congenital adrenal hyperplasia. J Clin Endocrinol Metab 2015;100:E1143\u201352.","DOI":"10.1210\/jc.2015-2232"},{"key":"2023033122552034940_j_jpem-2022-0396_ref_012","doi-asserted-by":"crossref","unstructured":"Schalkwijk, J, Zweers, MC, Steijlen, PM, Dean, WB, Taylor, G, van Vlijmen, IM, et al.. A recessive form of the Ehlers\u2013Danlos syndrome caused by tenascin-X deficiency. N Engl J Med 2001;345:1167\u201375.","DOI":"10.1056\/NEJMoa002939"}],"container-title":["Journal of Pediatric Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2022-0396\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2022-0396\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T12:17:28Z","timestamp":1680351448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/jpem-2022-0396\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":12,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,11,23]]},"published-print":{"date-parts":[[2023,1,27]]}},"alternative-id":["10.1515\/jpem-2022-0396"],"URL":"https:\/\/doi.org\/10.1515\/jpem-2022-0396","relation":{},"ISSN":["0334-018X","2191-0251"],"issn-type":[{"type":"print","value":"0334-018X"},{"type":"electronic","value":"2191-0251"}],"subject":[],"published":{"date-parts":[[2022,10,20]]}}}