Xiao Bing, Ji Xing, Xing Ya, Chen Ying-Wei, Tao Jiong
Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Genetics, Shanghai Institute for Pediatric Research, Shanghai, China.
Eur J Med Genet. 2013 Dec;56(12):695-8. doi: 10.1016/j.ejmg.2013.10.001. Epub 2013 Oct 18.
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.
46,XX性发育障碍（DSD）是一种罕见的遗传疾病。在此，我们报告一例46,XX SRY阴性且完全男性化的男性病例。对DAX1、SOX9和RSPO1基因的编码区及外显子/内含子边界进行了测序，未检测到突变。通过全基因组阵列分析和实时PCR，我们在SOX9上游约510 - 584 kb处（chr17:69,533,305 - 69,606,825，hg19）发现了一个约74 kb的重复序列。结合先前研究结果，与性腺发育相关的最小关键区域是位于SOX9上游584 - 517 kb处的一个67 kb区域。该区域的扩增可能导致SOX9过表达，从而引起女性向男性的性反转。SOX9上游区域的性腺特异性增强子可能通过远距离调控激活SOX9表达，进而触发睾丸分化。
