{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:01:59Z","timestamp":1753869719696,"version":"3.41.2"},"reference-count":27,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T00:00:00Z","timestamp":1732233600000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>High sequence homology between <jats:italic>CYP21A2<\/jats:italic> and <jats:italic>CYP21A1P<\/jats:italic> poses challenges to genetic diagnosis of congenital adrenal hyperplasia (CAH) due to 21\u2010hydroxylase deficiency (21\u2010OHD). Traditional genetic testing is unable to provide an accurate diagnosis due to the genetic complexity of CAH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Deletions, duplications, and recombination breakpoints were precisely identified by long\u2010read sequencing (LRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>This study presented a pregnant woman, a 21\u2010OHD carrier detected by MLPA, and her husband, a normal subject also detected by MLPA. The fetus was suspected of having 21\u2010OHD based on clinical presentations such as enlarged adrenal glands, atypical external genitalia and karyotyping of 46, XX. LRS further identified the fetus as having the most severe salt\u2010wasting (SW) form of 21\u2010OHD with a compound heterozygote genotype. One allele was <jats:italic>TNXA\/TNXB<\/jats:italic> CH\u20102, while the other allele was <jats:italic>CYP21A1P\/CYP21A2<\/jats:italic> CH\u20108. LRS precisely determined the genotypes of the fetus's father and grandmother with duplications, which misdiagnosed by MLPA. The multidisciplinary team recommended immediate glucocorticoid and mineralocorticoid treatment for the child after birth to prevent life\u2010threatening adrenal crisis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>LRS provides precise diagnosis for family members with <jats:italic>CYP21A2<\/jats:italic> deletion or duplication, improving disease management and preventing potential adrenal crises. When used in pre\u2010pregnancy genetic testing, LRS can indicate high genetic risk and guide the appropriate therapy during pregnancy and immediately after birth.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.70029","type":"journal-article","created":{"date-parts":[[2024,11,22]],"date-time":"2024-11-22T09:18:00Z","timestamp":1732267080000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Long\u2010Read Sequencing Identifying the Genetic Complexity of Congenital Adrenal Hyperplasia in the Pedigree"],"prefix":"10.1002","volume":"12","author":[{"given":"Ximin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Medical Genetics and Prenatal Diagnosis Sichuan Provincial Women's and Children's Hospital, the Affiliated Women's and Children's Hospital of Chengdu Medical College  Chengdu Sichuan 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