Résumé
THE testis-determining factor gene (
TDF
) lies on the Y chromosome and is responsible for initiating male sex determination.
SRY
is a gene located in the sex-determining region of the human and mouse Y chromosomes and has many of the properties expected for
TDF
l–3
Sex reversal in XY females results from the failure of the testis determination or differentiation pathways. Some XY females, with gonadal dysgenesis, have lost the sex-determining region from the Y chromosome by terminal exchange between the sex chromosomes
4
or by other deletions
5
. If
SRY
is
TDF
, it would be predicted that some sex-reversed XY females, without Y chromosome deletions, will have suffered mutations in
SRY
. We have tested human XY females and normal XY males for alterations in
SRY
using the single-strand conformation polymorphism assay
6,7
and subsequent DNA sequencing. A de novo mutation was found in the
SRY
gene of one XY female: this mutation was not present in the patient's normal father and brother. A second variant was found in the
SRY
gene of another XY female, but in this case the normal father shared the same alteration. The variant in the second case may be fortuitously associated with, or predisposing towards sex reversal; the de novo mutation associated with sex reversal provides compelling evidence that
SRY
is required for male sex determination.