Analysis of the testis-determining gene SRY in patients with XY gonadal dysgenesis.

The sex-determining region of the Y chromosome (SRY) encodes a gene that has many of the properties expected to the testis-determining factor. XY gonadal dysgenesis is characterized by streak gonads in phenotypic females who lack the somatic abnormalities and short stature associated with Turner's syndrome. We have examined four patients with XY gonadal dysgenesis for the presence and absence of SRY and the DNA sequence of the gene. The results showing that one was negative for SRY and another had a mutation within the gene have confirmed the etiological role of SRY in XY gonadal dysgenesis. However, the other two patients with short stature had apparently normal SRY. DNA sequencing of the SRY gene showed 100% nucleotide sequence identity with the reported cloned sequence. Sex reversal in two of the present cases may be due to mutation at a locus other than SRY in the sex-determining pathway, a gene potentially involved in the determination of human sexual constitution.