Duplication of the SOX3 gene in an SRY-negative boy with a 46,XX karyotype: a case report and a review of the literature

Abstract

46,XX testicular disorder of sex development (DSD), also known as XX male syndrome, is a rare condition where an individual with a 46,XX karyotype develops a male phenotype. In 90% of cases, the syndrome results from the translocation of the SRY gene to the X chromosome or an autosome. The remaining 10% of individuals lack the SRY gene. We report a case of an SRY- negative 3-year-old boy with a 46,XX karyotype exhibiting normal male external genitalia. Array CGH analysis revealed a 723-kb duplication of the Xq27.1q27.2 region, encompassing the SOX3 gene. The duplication was tandem. An imbalance in X chromosome methylation was observed, with a ratio of 4.5:1. The patient’s mother and grandmother, both with a 46,XX karyotype, were asymptomatic carriers of this duplication. To date, SOX3 duplication has been documented in 12 SRY- negative male patients and one female patient; eleven of these individuals exhibited various disorders of genital development. In contrast, only two previously reported patients displayed normal male genitalia, although associated with infertility. This case, the first reported in the Czech Republic, further supports the hypothesis that SOX3 overexpression during gonadal development, accompanied by imbalanced X-chromosome inactivation, may induce testis formation, thereby compensating for the absence of the SRY gene in SRY -negative 46,XX male patients.