{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:11:45Z","timestamp":1793059905548,"version":"4.5.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T00:00:00Z","timestamp":1655424000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research and Development Program of China","award":["2021YFC1005300"],"award-info":[{"award-number":["2021YFC1005300"]}]},{"name":"National Key Research and Development Program of China","award":["2017YFC1001802"],"award-info":[{"award-number":["2017YFC1001802"]}]},{"name":"Science and Technology Innovation Program of Hunan Province","award":["2019SK1010"],"award-info":[{"award-number":["2019SK1010"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81771599"],"award-info":[{"award-number":["81771599"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81974240"],"award-info":[{"award-number":["81974240"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder that has been included in newborn screening programs. Current approaches to gene testing for CAH are facing challenges because of the complexity of the CYP21A2 locus and genetic heterogeneity of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A comprehensive analysis of CAH (CACAH) combining long-range locus-specific PCR and long-read sequencing (LRS) was developed to perform full sequence analysis of 5 common CAH candidate genes, including CYP21A2, CYP11B1, CYP17A1, HSD3B2, and StAR. In a blind retrospective study, the clinical utility of CACAH was evaluated in 37 samples by comparing to standard CAH testing using multiplex ligation-dependent probe amplification (MLPA) plus Sanger sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of the 37 clinical samples, a total of 69 pathogenic variants were identified, comprising 65 CYP21A2 variants, 2 HSD3B2 variants, and 2 CYP17A1 variants. For CYP21A2, the most frequent variant was c.518T\u2009&amp;gt;\u2009A (29.2%), followed by c.293\u221213C\/A\u2009&amp;gt;\u2009G (21.5%). Compared with the current CAH testing using MLPA plus Sanger sequencing, the CACAH assay showed 100% specificity and 100% sensitivity, and precisely determined the junction sites of deletions\/insertions and cis\u2013trans configuration of multiple variants without analyzing family samples. Moreover, CACAH identified a case carrying 2 copies of CYP21A1 with the c.1451_1452delinsC variant on the same chromosome, which was not confirmed by MLPA plus Sanger sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LRS-based CACAH can determine all genotypes of CAH accurately and reliably in one assay, presenting a comprehensive approach for CAH genetic diagnosis and carrier screening.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/clinchem\/hvac046","type":"journal-article","created":{"date-parts":[[2022,3,11]],"date-time":"2022-03-11T07:08:13Z","timestamp":1646982493000},"page":"927-939","source":"Crossref","is-referenced-by-count":81,"title":["Comprehensive Analysis of Congenital Adrenal Hyperplasia Using Long-Read Sequencing"],"prefix":"10.1093","volume":"68","author":[{"given":"Yingdi","family":"Liu","sequence":"first","affiliation":[{"name":"Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University , 110 Xiangya Road, Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University , 110 Xiangya Road, Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital , Changsha 410078, Hunan , China"},{"name":"National Health Commission Key Laboratory of Birth Defects Research, Prevention and Treatment , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Mao","sequence":"additional","affiliation":[{"name":"Berry Genomics Corporation , Beijing 102200 , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanling","family":"Teng","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University , 110 Xiangya Road, Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiming","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hunan Provincial Maternal and Child Health Care Hospital , Changsha 410078, Hunan , China"},{"name":"National Health Commission Key Laboratory of Birth Defects Research, Prevention and Treatment , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University , 110 Xiangya Road, Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University , 110 Xiangya Road, Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University , 110 Xiangya Road, Changsha 410078, Hunan , China"},{"name":"Department of Medical Genetics, Hunan Jiahui Genetics Hospital , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingqian","family":"Wu","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University , 110 Xiangya Road, Changsha 410078, Hunan , China"},{"name":"Department of Medical Genetics, Hunan Jiahui Genetics Hospital , Changsha 410078, Hunan , China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,6,17]]},"reference":[{"key":"2022070317170460500_hvac046-B1","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1016\/S0140-6736(17)31431-9","article-title":"Congenital adrenal 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