title: A rare case of 46, XX SRY-negative male with approximately 74-kb duplication in a region upstream of SOX9.
abstract: The 46, XX male disorder of sex development (DSD) is a rare genetic condition. Here, we report the case of a 46, XX SRY-negative male with complete masculinization. The coding region and exon/intron boundaries of the DAX1, SOX9 and RSPO1 genes were sequenced, and no mutations were detected. Using whole genome array analysis and real-time PCR, we identified a approximately 74-kb duplication in a region approximately 510-584 kb upstream of SOX9 (chr17:69,533,305-69,606,825, hg19). Combined with the results of previous studies, the minimum critical region associated with gonadal development is a 67-kb region located 584-517 kb upstream of SOX9. The amplification of this region might lead to SOX9 overexpression, causing female-to-male sex reversal. Gonadal-specific enhancers in the region upstream of SOX9 may activate the SOX9 expression through long-range regulation, thus triggering testicular differentiation.
authors.affiliation: Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute for Pediatric Research, Shanghai, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.forename: Xing
authors.initials: X
authors.lastname: Ji
authors.forename: Ya
authors.initials: Y
authors.lastname: Xing
authors.forename: Ying-Wei
authors.initials: YW
authors.lastname: Chen
authors.forename: Jiong
authors.initials: J
authors.lastname: Tao
mesh_terms: D000328:Adult; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics; D020440:Gene Duplication; D023961:Gonadal Dysgenesis, 46,XX / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D055758:SOX9 Transcription Factor / Q000235:genetics*; D019699:Thrombospondins / Q000235:genetics; D000098907:R-Spondins
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D055758:SOX9 Transcription Factor; D019699:Thrombospondins; C539965:NR0B1 protein, human; C503243:RSPO1 protein, human; D000098907:R-Spondins; C527932:SOX9 protein, human
keywords: 46, XX male; Disorder of sex development; SOX9; SRY-negative