{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:41:52Z","timestamp":1785804112499,"version":"3.56.0"},"reference-count":19,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,8]],"date-time":"2023-05-08T00:00:00Z","timestamp":1683504000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Congenital adrenal hyperplasia (CAH) due to 21\u2010hydroxylase (21OH) deficiency is an autosomal recessive inborn error of cortisol biosynthesis, with varying degrees of aldosterone production. There is a continuum of phenotypes which generally correlate with genotype and the expected residual 21OH activity of the less severely impaired allele. <jats:italic>CYP21A1P\/CYP21A2<\/jats:italic> chimeric genes caused by recombination between <jats:italic>CYP21A2<\/jats:italic> and its highly homologous <jats:italic>CYP21A1P<\/jats:italic> pseudogene are common in CAH and typically associated with salt\u2010wasting CAH, the most severe form. Nine chimeras have been described (CH\u20101 to CH\u20109).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>The aim of this study was to genetically evaluate two variant alleles carried by a 22\u2010year\u2010old female with the non\u2010salt\u2010wasting simple virilizing form of CAH and biallelic 30\u2010kb deletions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The haplotypes of the <jats:italic>CYP21A2<\/jats:italic> heterozygous variants, as well as the chimeric junction sites, were determined by Sanger sequencing TA clones of an allele\u2010specific PCR product.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Genetic testing revealed two rare <jats:italic>CYP21A1P\/CYP21A2<\/jats:italic> chimeras: allele 1 matches the previously described CAH CH\u20101 chimera but without the P30L variant, and allele 2, termed here as novel CAH CH\u201010, has a junction site between c.293\u201037 and c.29314, which is expected to retain partial 21OH activity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These two variant alleles further document the complex nature of RCCX modules and highlight that not all <jats:italic>CYP21A1P\/CYP21A2<\/jats:italic> chimera severely impair 21OH activity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2195","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T06:39:55Z","timestamp":1683614395000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Congenital adrenal hyperplasia due to two rare <i>CYP21A2<\/i> variant alleles, including a novel attenuated <i>CYP21A1P<\/i>\/<i>CYP21A2<\/i> chimera"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1816-134X","authenticated-orcid":false,"given":"Qizong","family":"Lao","sequence":"first","affiliation":[{"name":"National Institutes of Health Clinical Center  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1743-7503","authenticated-orcid":false,"given":"Deepika D.","family":"Burkardt","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6114-6885","authenticated-orcid":false,"given":"Sarah","family":"Kollender","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7959-9842","authenticated-orcid":false,"given":"Fabio R.","family":"Faucz","sequence":"additional","affiliation":[{"name":"The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-0460","authenticated-orcid":false,"given":"Deborah P.","family":"Merke","sequence":"additional","affiliation":[{"name":"National Institutes of Health Clinical Center  Bethesda Maryland USA"},{"name":"The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health  Bethesda Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102265.2005.02184.x"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431\u2010020\u20100653\u20105"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.709758"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2011.174037"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471\u20102350\u201011\u2010104"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/js.2019\u201000122"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2010\u20100319"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.13370"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.46"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1525\u20101578(10)60550\u20108"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.85.3.6441"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.85.12.7018"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1909786"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012\u20103148"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.612497"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2019.00432"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.785570"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2012.06.045"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmoldx.2013.06.001"}],"container-title":["Molecular Genetics &amp; Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mgg3.2195","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T14:18:19Z","timestamp":1692281899000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mgg3.2195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,8]]},"references-count":19,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1002\/mgg3.2195"],"URL":"https:\/\/doi.org\/10.1002\/mgg3.2195","archive":["Portico"],"relation":{},"ISSN":["2324-9269","2324-9269"],"issn-type":[{"value":"2324-9269","type":"print"},{"value":"2324-9269","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,8]]},"assertion":[{"value":"2022-12-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2195"}}