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However, reaching a specific diagnosis using traditional approaches can be difficult, especially in adults where limited biochemical data may be available.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We used a targeted next-generation sequencing approach to analyze known and candidate genes for DSDs in individuals with no specific molecular diagnosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants and Design<\/jats:title><jats:p>We studied 52 adult 46,XY women attending a single-center adult service, who were part of a larger cohort of 400 individuals. Classic conditions such as17\u03b2-hydroxysteroid dehydrogenase deficiency type 3, 5\u03b1-reductase deficiency type 2, and androgen insensitivity syndrome were excluded. The study cohort had broad working diagnoses of complete gonadal dysgenesis (CGD) (n = 27) and partially virilized 46,XY DSD (pvDSD) (n = 25), a group that included partial gonadal dysgenesis and those with a broad \u201cpartial androgen insensitivity syndrome\u201d label. Targeted sequencing of 180 genes was undertaken.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, a likely genetic cause was found in 16 of 52 (30.8%) individuals (22.2% CGD, 40.0% pvDSD). Pathogenic variants were found in sex-determining region Y (SRY; n = 3), doublesex and mab-3\u2013related transcription factor 1 (DMRT1; n = 1), NR5A1\/steroidogenic factor-1 (SF-1) (n = 1), and desert hedgehog (DHH; n = 1) in the CGD group, and in NR5A1 (n = 5), DHH (n = 1), and DEAH-box helicase 37 (DHX37; n = 4) in the pvDSD group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Reaching a specific diagnosis can have clinical implications and provides insight into the role of these proteins in sex development. Next-generation sequencing approaches are invaluable, especially in adult populations or where diagnostic biochemistry is not possible.<\/jats:p><\/jats:sec>","DOI":"10.1210\/js.2019-00306","type":"journal-article","created":{"date-parts":[[2019,10,10]],"date-time":"2019-10-10T22:03:22Z","timestamp":1570745002000},"page":"2341-2360","source":"Crossref","is-referenced-by-count":69,"title":["Next-Generation Sequencing Reveals Novel Genetic Variants (SRY, DMRT1, NR5A1, DHH, DHX37) in Adults With 46,XY DSD"],"prefix":"10.1210","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8274-7241","authenticated-orcid":false,"given":"Federica","family":"Buonocore","sequence":"first","affiliation":[{"name":"Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health, University College London, London, United 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