Description and functional implications of a novel mutation in the sex-determining gene SRY

Abstract
The sex‐determining gene SRY was screened for molecular alteration in an XY sex‐reversed female by single‐strand conformation polymorphism (SSCP) technique. An A‐to‐G transition was detected which leads to an exchange of a tyrosine by a cysteine in the SRY protein. The affected tyrosine residue located at the C terminus of the DNA binding protein is evolutionarily strongly conserved among the members of the HMG box containing proteins. Using gel shift assay and peptide synthesis such a mutation is shown to abolish the SRY protein DNA binding ability. The involvement of this particular amino acid in the binding specificity is also discussed.