3 NOVEL SRY MUTATIONS IN XY GONADAL-DYSGENESIS AND THE ENIGMA OF XY GONADAL-DYSGENESIS CASES WITHOUT SRY MUTATIONS

Mutations in the Y-located testis-determining gene SRY are one cause f or XY sex reversal. We have previously identified four SRY mutations i n a total of 45 sex-reversed females with XY gonadal dysgenesis (XY GD ). In a new sample of 16 XY GD cases, three previously undescribed SRY mutations were identified. Two are point mutations that lead to amino acid substitutions in the HMG domain of SRY, M64R, and F67V, The thir d SRY mutation is a single base insertion 5' to the HMG box within cod on 43, converting this lysine codon to a stop codon (K43X). A total of 33 SRY mutations have so far been described that account for only 10- 15% of XY CD females. A further 10-15 % of these cases result from del etion of SRY due to aberrant X/Y interchange. The etiology of the rema ining 70-80% of XY GD cases is still enigmatic. Possible explanations for these XY sex-reversal cases are discussed.