{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:18:43Z","timestamp":1791944323328,"version":"4.3.4"},"reference-count":103,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Congenital adrenal hyperplasia (CAH) can result from variants in several genes but is most frequently caused by deletions and gene conversions in the segmentally duplicated RCCX module, which contains the CYP21A2 gene and its pseudogene. Current genetic tests vary greatly by laboratory, method, and consequently diagnostic ability. Less severe forms of CAH are frequently underdiagnosed or misdiagnosed, and phenotype\/genotype correlations remain incomplete, hampering genetic counseling and prediction of long-term outcomes.<\/jats:p>\n                  <jats:p>Emerging technologies using long-read sequencing (LRS) have transformed molecular testing for CAH, accurately identifying pathogenic single-nucleotide variants (SNVs), full-gene deletions, gene conversions, fusions creating nonfunctional hybrids between the gene and pseudogene (\u201c30-kb deletion\u201d), and phasing variants, even in the absence of parental samples. This has led to updated reports of previously unrecognized complex alleles in large cohorts.<\/jats:p>\n                  <jats:p>This is a transformative breakthrough, which offers the promise of consolidated testing for all forms of CAH and other conditions under the differences of sex development (DSDs) umbrella. DSDs are notoriously difficult to disambiguate, resulting in a considerable diagnostic gap. The large array of known genetic etiology, ranging from SNVs in coding or noncoding regions in dozens of genes to sex chromosome aneuploidies, associated with overlapping phenotypes, make precise DSD diagnosis one of the most difficult in medicine. We report on our experience with LRS tools for disambiguation of CAH alleles and discuss some of the technical aspects to be considered prior to the deployment of LRS to ensure accurate and equitable results for the diagnosis of rare conditions such as DSDs.<\/jats:p>","DOI":"10.1210\/clinem\/dgag390","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T07:50:12Z","timestamp":1790149812000},"source":"Crossref","is-referenced-by-count":1,"title":["Leveraging long-read sequencing to bridge the diagnostic and equity gaps in differences of sex development"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3541-3190","authenticated-orcid":false,"given":"Emmanu\u00e8le C","family":"D\u00e9lot","sequence":"first","affiliation":[{"name":"Institute for Clinical and Translational Science, University of California Irvine , Irvine, CA 92697 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5557-3709","authenticated-orcid":false,"given":"Eric","family":"Vilain","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Translational Science, University of California Irvine , Irvine, CA 92697 ,","place":["USA"]},{"name":"UCI School of Medicine Department of Pediatrics, , Orange, CA 92868 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"issue":"9","key":"2026101310370658400_dgag390-B1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/s41576-021-00365-5","article-title":"Towards improved genetic diagnosis of human differences of sex development","volume":"22","author":"D\u00e9lot","year":"2021","journal-title":"Nat Rev Genet"},{"issue":"2","key":"2026101310370658400_dgag390-B2","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1542\/peds.2006-0738","article-title":"Consensus statement on management of intersex disorders","volume":"118","author":"Lee","year":"2006","journal-title":"Pediatrics"},{"issue":"7","key":"2026101310370658400_dgag390-B3","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.3390\/ijms21072282","article-title":"Disorders of sex development-novel regulators, impacts on fertility, and options for fertility preservation","volume":"21","author":"Gomes","year":"2020","journal-title":"Int J Mol Sci"},{"issue":"2","key":"2026101310370658400_dgag390-B4","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1159\/000502644","article-title":"Gonadal tissue cryopreservation for children with differences of sex development","volume":"92","author":"Johnson","year":"2019","journal-title":"Horm Res Paediatr"},{"issue":"20","key":"2026101310370658400_dgag390-B5","doi-asserted-by":"crossref","first-page":"5017","DOI":"10.3390\/ijms20205017","article-title":"Predicting gonadal germ cell cancer in people with disorders of sex development; 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