A duplication upstream of SOX9 was not positively correlated with the SRY‑negative 46,XX testicular disorder of sex development: A case report and literature review.
By CNV analysis, we identified SOX9 upstream duplications in three cases of SRY-negative 46,XX DSD, which together with previously reported duplications define a 68 kb region, 516-584 kb upstream of SOX9, designated XXSR (XX sex reversal region).
We previously reported 5 cases of SRY-negative 46,XX testicular disorders of sex development and demonstrated that coordinated expression of genes such as SOX9, SOX3, and DAX1 was associated with testicular development.
Thus, the 12;17 translocation removed part of the SOX9 cis-regulatory region and replaced it with a regulatory element from pseudogene LOC204010 or the next gene, Deynar, of chromosome 12, potentially causing up-regulation of the testis-determining SOX9 gene during gonadal development and the phenotype of 46,XX testicular DSD.
Together, these findings implicate a mutation at a sex-determining locus other than SRY and SOX9 as the cause for the XX sex reversal trait in this family.