A NOVEL MISSENSE MUTATION (S18N) IN THE 5'-NON-HMG BOX REGION OF THE SRY GENE IN A PATIENT WITH PARTIAL GONADAL-DYSGENESIS AND HIS NORMAL-MALE RELATIVES

Mutations in the sex-determining region of the Y chromosome (the SRY g ene) have been reported in low frequency in patients with 46,XY gonada l dysgenesis. We investigated 21 Brazilian 46,XY sex-reversed patients , who presented either complete or partial gonadal dysgenesis or embry onic testicular regression syndrome. Using Southern blotting, polymera se chain reaction, denaturing gradient gel electrophoresis and direct sequencing, we analyzed deletions and point mutations in the SRY gene, We found a missense mutation at codon 18 upstream of the 5' border of the HMG box of the SRY gene in one patient with partial gonadal dysge nesis. This variant sequence was also found in DNA obtained from blood and sperm cells of his father and in blood cells of his normal brothe r. The S18N mutation was not found in 50 normal males, ruling out the possibility of a common polymorphism. We identified a novel familial m issense mutation (S18N) in the 5' non-HMG box of the SRY gene in 1 of 21 patients with 46,XY sex reversal.