{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T16:01:13Z","timestamp":1790524873909,"version":"4.1.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Congenital adrenal hyperplasia (CAH) secondary to 21-hydroxylase deficiency is an autosomal recessive disorder. The 21-hydroxylase enzyme P450c21 is encoded by the <jats:italic>CYP21A2<\/jats:italic> gene located on chromosome 6p21.33 within the HLA major histocompatibility complex. This locus also contains the <jats:italic>CYP21A1P<\/jats:italic>, a non-functional pseudogene, that is highly homologous to the <jats:italic>CYP21A2<\/jats:italic> gene. Other duplicated genes are <jats:italic>C4A<\/jats:italic> and <jats:italic>C4B<\/jats:italic>, that encode two isoforms of complement factor C4, the <jats:italic>RP1<\/jats:italic> gene that encodes a serine\/threonine protein kinase, and the <jats:italic>TNXB<\/jats:italic> gene that, encodes the extracellular matrix glycoprotein tenascin-X (TNX). TNX plays a role in collagen deposition by dermal fibroblasts and is expressed in the dermis of the skin and the connective tissue of the heart and skeletal muscle. During meiosis, misalignment may occur producing large gene deletions or gene conversion events resulting in chimeric genes. Chimeric recombination may occur between <jats:italic>TNXB<\/jats:italic> and <jats:italic>TNXA.<\/jats:italic> Three <jats:italic>TNXA\/TNXB<\/jats:italic> chimeras have been described that differ in the junction site (CH1 to CH3) and result in a contiguous <jats:italic>CYP21A2<\/jats:italic> and <jats:italic>TNXB<\/jats:italic> gene deletion, causing CAH-X syndrome. <jats:italic>TNXB<\/jats:italic> deficiency is associated with Ehlers Danlos syndrome (EDS). EDS comprises a clinically and genetically heterogeneous group of connective tissue disorders. As molecular analysis of the <jats:italic>TNXB<\/jats:italic> gene is challenging, the TNX-deficient type EDS is probably underdiagnosed. In this minireview, we will address the different strategies of molecular analysis of the <jats:italic>TNXB<\/jats:italic>-gene, as well as copy number variations and genetic status of <jats:italic>TNXB<\/jats:italic> in different cohorts. Furthermore, clinical features of EDS and clinical recommendations for long-term follow-up are discussed.<\/jats:p>","DOI":"10.3389\/fendo.2022.803226","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T05:24:42Z","timestamp":1645766682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Congenital Adrenal Hyperplasia and Ehlers-Danlos Syndrome"],"prefix":"10.3389","volume":"13","author":[{"given":"Roxana","family":"Marino","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang\u00e9lica","family":"Moresco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Perez Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Ramirez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Belgorosky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra021561","article-title":"Congenital Adrenal Hyperplasia","volume":"349","author":"Speiser","year":"2003","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","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"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2010\/625105","article-title":"Nonclassic Congenital Adrenal Hyperplasia","volume":"2010","author":"Witchel","year":"2010","journal-title":"Int J Pediatr Endocrinol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.9.2841","article-title":"Complete Nucleotide Sequence of Two Steroid 21-Hydroxylase Genes Tandemly Arranged in Human Chromosome: A Pseudogene and a Genuine Gene","author":"Higashi","year":"1986","journal-title":"Proc Natl Acad Sci USA"},{"key":"B5","doi-asserted-by":"publisher","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). 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