{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:01:36Z","timestamp":1769522496627,"version":"3.49.0"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T00:00:00Z","timestamp":1653350400000},"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:sec><jats:title>Objective<\/jats:title><jats:p>11\u03b2-Hydroxylase deficiency (11\u03b2-OHD) caused by mutations in the <jats:italic>CYP11B1<\/jats:italic> gene is the second most common form of congenital adrenal hyperplasia. Both point mutations and genomic rearrangements of <jats:italic>CYP11B1<\/jats:italic> are important causes of 11\u03b2-OHD. However, the high degree of sequence identity between <jats:italic>CYP11B1<\/jats:italic> and its homologous gene <jats:italic>CYP11B2<\/jats:italic>, presents unique challenges for molecular diagnosis of suspected 11\u03b2-OHD. The aim of this study was to detect the point mutation, indel, small deletion of <jats:italic>CYP11B1<\/jats:italic> and chimeric <jats:italic>CYP11B2<\/jats:italic>\/<jats:italic>CYP11B1<\/jats:italic> gene in a one-tube test, improving the genetic diagnosis of 11\u03b2-OHD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Optimized custom-designed target sequencing strategy was performed in three patients with suspected 11\u03b2-OHD, in which both the coverage depth of paired-end reads and the breakpoint information of split reads from sequencing data were analysed in order to detect genomic rearrangements covering <jats:italic>CYP11B1<\/jats:italic>. Long-range PCR was peformed to validate the speculated <jats:italic>CYP11B1<\/jats:italic> rearrangements with the breakpoint-specifc primers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Using the optimized target sequencing approach, we detected two intragenic\/intergenic deletions of <jats:italic>CYP11B1<\/jats:italic> and one chimeric <jats:italic>CYP11B2<\/jats:italic>\/<jats:italic>CYP11B1<\/jats:italic> gene from three suspected patients with 11\u03b2-OHD besides three pathogenic heterozygous point mutation\/indels. Furthermore, we mapped the precise breakpoint of this chimeric <jats:italic>CYP11B2<\/jats:italic>\/<jats:italic>CYP11B1<\/jats:italic> gene located on chr8:143994517 (hg19) and confirmed it as a founder rearrangement event in the Chinese population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our optimized target sequencing approach improved the genetic diagnosis of 11\u03b2-OHD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2022.882863","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T10:46:03Z","timestamp":1653389163000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Detection of Small CYP11B1 Deletions and One Founder Chimeric CYP11B2\/CYP11B1 Gene in 11\u03b2-Hydroxylase Deficiency"],"prefix":"10.3389","volume":"13","author":[{"given":"Hua","family":"Xie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Yin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Na","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoli","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaobo","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-18-0279","article-title":"MECHANISMS IN ENDOCRINOLOGY: Rare Defects in Adrenal Steroidogenesis","volume":"179","author":"Miller","year":"2018","journal-title":"Eur J Endocrinol"},{"key":"B2","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":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2008.10.014","article-title":"Genetics of Congenital Adrenal Hyperplasia","volume":"23","author":"Krone","year":"2009","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1621082114","article-title":"Clinical, Genetic, and Structural Basis of Congenital Adrenal Hyperplasia Due to 11beta-Hydroxylase Deficiency","volume":"114","author":"Khattab","year":"2017","journal-title":"Proc Natl Acad Sci USA"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-56-2-222","article-title":"Clinical and Biochemical Variability of Congenital Adrenal Hyperplasia Due to 11 Beta-Hydroxylase Deficiency. 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