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Leventis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004117","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hormones"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract\n<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Genetic diversity of mutations in the <jats:italic>CYP21A2<\/jats:italic> gene is the main cause of the monogenic congenital adrenal hyperplasia (CAH) disorder. On chromosome 6p21.3, the <jats:italic>CYP21A2<\/jats:italic> gene is partially overlapped by the <jats:italic>TNXB<\/jats:italic> gene, the two residing in tandem with their highly homologous corresponding pseudogenes (<jats:italic>CYP21A1P<\/jats:italic> and <jats:italic>TNXA<\/jats:italic>), which leads to recurrent homologous recombination.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods and results<\/jats:title>\n                <jats:p>In the present study, the genetic status of an ethnic Greek-Cypriot family, with a female neonate that was originally classified as male and manifested the salt-wasting (SW) form, is presented. Genetic defects in the <jats:italic>CYP21A2<\/jats:italic> and <jats:italic>TNXB<\/jats:italic> genes were investigated by Sanger sequencing multiplex ligation-dependent probe amplification (MLPA) and a real-time PCR assay. The neonate carried in compound heterozygosity the <jats:italic>TNXA\/TNXB<\/jats:italic> chimeric gene complex (termed CAH-X CH-1) that results in a contiguous <jats:italic>CYP21A2<\/jats:italic> and <jats:italic>TNXB<\/jats:italic> deletion and in her second allele the pathogenic IVS2-13A\/C\u2009&gt;\u2009G (c.655A\/C\u2009&gt;\u2009G) in <jats:italic>CYP21A2<\/jats:italic>.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>The classic SW-CAH due to 21-hydroxylase (21-OH) deficiency may result from various complex etiological mechanisms and, as such, can involve the formation of monoallelic <jats:italic>TNXA\/TNXB<\/jats:italic> chimeras found <jats:italic>in trans<\/jats:italic> with other <jats:italic>CYP21A2<\/jats:italic> pathogenic variants. This is a rare case of CAH due to 21-hydroxylase deficiency, which elucidates the role of the complex RCCX CNV structure in the development of the disease. Identification of the correct CAH genotypes for a given phenotype is of considerable value in assisting clinicians in prenatal diagnosis, appropriate treatment, and genetic counseling.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s42000-022-00410-w","type":"journal-article","created":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T13:03:57Z","timestamp":1666271037000},"page":"71-77","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Salt-wasting congenital adrenal hyperplasia phenotype as a result of the TNXA\/TNXB chimera 1 (CAH-X CH-1) and the pathogenic IVS2-13A\/C\u2009&gt;\u2009G in CYP21A2 gene"],"prefix":"10.1007","volume":"22","author":[{"given":"Pavlos","family":"Fanis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicos","family":"Skordis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonidas A.","family":"Phylactou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vassos","family":"Neocleous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"issue":"1","key":"410_CR1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1210\/endrev\/bnab016","volume":"43","author":"HL Claahsen-van der Grinten","year":"2022","unstructured":"Claahsen-van der Grinten HL, Speiser PW, Ahmed SF, Arlt W, Auchus RJ, Falhammar H, Fluck CE, Guasti L, Huebner A, Kortmann BBM, Krone N, Merke DP, Miller WL, Nordenstrom A, Reisch N, Sandberg DE, Stikkelbroeck N, Touraine P, Utari A, Wudy SA, White PC (2022) Congenital adrenal hyperplasia-current insights in pathophysiology, diagnostics, and management. 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