{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:45:46Z","timestamp":1792788346352,"version":"4.5.0"},"reference-count":23,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"CAMS Innovation Fund for Medical Sciences","award":["CIFMS 2021-I2M-1-003"],"award-info":[{"award-number":["CIFMS 2021-I2M-1-003"]}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-D-002"],"award-info":[{"award-number":["2022-PUMCH-D-002"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81971375"],"award-info":[{"award-number":["81971375"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>21-Hydroxylase deficiency (21-OHD) is caused by pathogenic variants in CYP21A2. High homology between CYP21A2 and its pseudogene CYP21A1P causes mismatches, leading to deletions and CYP21A1P\/CYP21A2 chimeras.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To detect chimeric CYP21A1P\/CYP21A2 in 21-OHD patients using long-read sequencing (LRS) and analyze genotype-phenotype correlations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>From 2015 to 2023, 869 21-OHD patients were enrolled at Peking Union Medical College Hospital, with 113 identified harboring CYP21A2 large deletion. Long-range PCR and LRS were used to identify the types of CYP21A1P\/CYP21A2 chimeric. Haplotype analysis explored founder effects, and in vitro assays assessed the functional impact of novel mutations. Clinical data were retrospectively collected and patients were classified into 4 groups based on genotypes and residual enzyme activity to study genotype-phenotype correlations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten types of chimeric CYP21A1P\/CYP21A2 genes were identified across 119 alleles, including a novel type, CH-10. The most common, CH-1, accounted for 50.4% of all types. Haplotype analysis of 24 SNPs within CYP21A1P\/CYP21A2 CH-1 revealed 25 haplotypes, with haplotype 11 being the most prevalent. Variants p.L100P and p.L301V of CYP21A2 showed enzyme activities of 1.36 \u00b1 0.44% or 1.63 \u00b1 0.19% for 17-hydroxyprogesterone to 11-deoxycortisol, and 1.36 \u00b1 0.58% or 3.99 \u00b1 1.09% for progesterone to 11-deoxycorticosterone, respectively, linked to the simple virilizing type. Genotype-phenotype consistency rates were 78.6% to 84% across the 4 groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LRS is a comprehensive genetic testing method for 21-OHD patients, effectively detecting both CYP21A2 gene variants and CYP21A1P\/CYP21A2 chimeric gene types. This study expands the CYP21A2 variant spectrum by identifying a novel chimera. Haplotype analysis revealed diverse haplotypes for each chimeric gene type, suggesting the absence of a common founder effect. The strong genotype-phenotype correlation aids genetic counseling and supports personalized treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgae819","type":"journal-article","created":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T23:15:46Z","timestamp":1738451746000},"page":"e3322-e3333","source":"Crossref","is-referenced-by-count":5,"title":["Chimeric\n                    <i>CYP21A1P\/CYP21A2<\/i>\n                    Genes in 21-Hydroxylase Deficiency Detected by Long-Read Sequencing and Phenotypes Correlation"],"prefix":"10.1210","volume":"110","author":[{"given":"Xiaoxia","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, National Health Commission (NHC) Key Laboratory of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences , Beijing 100730 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