Identification of a novel mutation in the SRY gene in a 46, XY female patient.

Background: The SRY gene encodes for a testis-specific transcription factor (TDF, testis determining factor) that plays a key role in sexual differentiation and development in males. Several SRY mutations have been described in patients with gonadal dysgenesis, accounting for 10-15% of the sex reversal cases. The reported mutations are both point mutations and deletions, mostly involving the high mobility group (HMG) box domain of SRY, which is a conserved region through the evolution, suggesting that SRY function strictly depends on the HMG box.

Case Presentation: Here we describe the clinical, endocrinological and molecular data of a patient with complete 46, XY gonadal dysgenesis caused by SRY mutation located within the conserved HMG box. Using DNA direct sequencing of the SRY coding region, we identified a single nucleotide insertion at codon 89 with subsequent frameshift of the reading frame sequence, which results in a truncated protein as consequence of an introduction of a stop codon at the position 103.

Conclusion: A novel SRY mutation has been described in a female with a gonadal dysgenesis associated with a 46, XY karyotype. The described case is of importance for genetic counseling.