In this study, we report that a novel missense mutation in the SRY gene, a G to A transition within the HMG box, causes the Ala66Thr amino acid substitution in a female patient presenting 46,XY karyotype with pure gonadal dysgenesis.
This constitutes the first report where mutations of DHH are associated with the presence of 46,XY complete PGD, demonstrating that the genetic origin of this entity is heterogeneous and that disorders in other genes, different from SRY, involved in the testis-determining pathway are implicated in abnormal testicular differentiation in humans.
This substitution affects a highly conserved tyrosine residue in the HMG box of SRY, in which two de novo mutations have been described previously in XY females with PGD.
We tested a female patient with 46,XY karyotype and pure gonadal dysgenesis for the presence of the SRY gene and for mutations within the SRY conserved domain.
Here, we distinguish between these activities by analysis of a mutant SRY associated with human sex reversal (46, XY female with pure gonadal dysgenesis).
These data indicate that the majority of XY females with pure gonadal dysgenesis owe their sex-reversed phenotype to mutations in as yet uncharacterised segments of the SRY gene, or, at other loci acting early in the sex-determining pathway.
Here we describe an XY sex-reversed female with pure gonadal dysgenesis who harbors a de novo nonsense mutation in the SRY open reading frame (SRY-orf).
Although the occurrence of pure gonadal dysgenesisPGD is usually sporadic and nonfamilial, here we present 3 sisters with 46, XX PGD, who are born from a first cousin marriage.