Background: Ovotesticular DSD is a rare disorder defined by the presence of both ovarian and testicular tissues in the same individual. SRY is present in approximately 1/3 of patients with 46, XX ovotesticular DSD. In SRY-negative ovotesticular DSD, the mechanism responsible for the presence of testicular tissue is not yet understood.
Case presentation: A male patient was referred to us for hypospadias and bilateral cryptorchidism at 2.5 years of age. He had a trophic phallus (32×13 mm) with coronal hypospadias and hypoplastic scrotum. Right gonad was palpable in the inguinal region; no gonad was palpable on the left side. Basal AMH (216 pmol/l) and hCG-stimulated testosterone (30 ng/dl) were low, indicating that dysgenetic testicular tissue was present. Gonadotrophins were not elevated, with FSH predominance (LH <0.10 U/L, FSH 0.73 U/L). Karyotype was 46, XX. These results were suggestive of the presence of ovarian tissue. Diagnostic laparoscopy was performed, and the histopathological study confirmed the presence of bilateral ovotestes. Absence of SRY in peripheral leukocytes was documented by QF PCR analysis (Devyser Kit). A genome-wide copy number analysis, performed by single-nucleotide polymorphism using CytoSNP-850K microarray (Illumina), confirmed the absence of SRY and of Y chromosome sequences. Furthermore, a de novo duplication of 502, 127 bp at Xq27.1 chromosomal region encompassing SOX3 gene was evidenced. Metaphase FISH analysis using a BAC probe hybridizing on both X homologues demonstrated a tandem duplication of this region.
Conclusion and discussion: This is the first case of SRY-negative 46, XX Ovotesticular DSD in whom a genetic association (SOX3 duplication) is reported. These results are in line with evidence in mice indicating that, in the absence of SRY, gain-of-function of SOX3 induces testis differentiation in the XX bipotential gonad. SOX3, as a surrogate of SRY, would act synergistically with SF1 to upregulate SOX9 expression and stimulate testicular organogenesis.
Funding: This work was partially financed by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina.