PURPOSE: The mammalian sex determining gene, sex region Y chromosome (SRY), is now firmly established as the testis determining locus. The SRY locus is close to the short arm Y terminus and just distal to zinc finger Y region (ZFY), a locus previously thought to be involved in testicular differentiation and the male phenotype. We report on XX sex reversal, a rare sex chromosomal disorder in humans. MATERIALS AND METHODS: Routine amniocentesis revealed an XX fetal karyotype, although at birth the neonate was phenotypically male. Radiographic evaluation showed a normal male urethra and the absence of any female internal genitalia. Subsequent molecular analysis with polymerase chain reaction amplified sequences of the SRY and ZFY loci were positive. RESULTS: This case is the fourth in our series of XX sex reversed male individuals and to our knowledge the first to be diagnosed perinatally. In all cases the SRY and ZFY loci are present, presumably on the paternal X chromosome, as well as a Klinefelter phenotype. These sex reversing translocations are thought to be due to an unequal meiotic recombination of the distal X and Y short arms during male gametogenesis. The tendency for XY translocations to break between the SRY and ZFY loci was not seen in these apparent microtranslocation cases. CONCLUSIONS: These 4 cases demonstrate the usefulness of molecular followup of clinically perplexing sexual discordance. We conclude that SRY and ZFY polymerase chain reaction amplification studies should be performed when sexual discrepancies are noted on prenatal ultrasound and karyotype analysis.
PURPOSE: The mammalian sex determining gene, sex region Y chromosome (SRY), is now firmly established as the testis determining locus. The SRY locus is close to the short arm Y terminus and just distal to zinc finger Y region (ZFY), a locus previously thought to be involved in testicular differentiation and the male phenotype. We report on XX sex reversal, a rare sex chromosomal disorder in humans. MATERIALS AND METHODS: Routine amniocentesis revealed an XX fetal karyotype, although at birth the neonate was phenotypically male. Radiographic evaluation showed a normal male urethra and the absence of any female internal genitalia. Subsequent molecular analysis with polymerase chain reaction amplified sequences of the SRY and ZFY loci were positive. RESULTS: This case is the fourth in our series of XX sex reversed male individuals and to our knowledge the first to be diagnosed perinatally. In all cases the SRY and ZFY loci are present, presumably on the paternal X chromosome, as well as a Klinefelter phenotype. These sex reversing translocations are thought to be due to an unequal meiotic recombination of the distal X and Y short arms during male gametogenesis. The tendency for XY translocations to break between the SRY and ZFY loci was not seen in these apparent microtranslocation cases. CONCLUSIONS: These 4 cases demonstrate the usefulness of molecular followup of clinically perplexing sexual discordance. We conclude that SRY and ZFY polymerase chain reaction amplification studies should be performed when sexual discrepancies are noted on prenatal ultrasound and karyotype analysis.