XX-SEX REVERSAL - MOLECULAR ANALYSIS OF THE SRY ZFY-REGIONS/

Purpose: The mammalian sex determining gene, sex region Y chromosome ( SRY), is now firmly established as the testis determining locus. The S RY 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 te sticular differentiation and the male phenotype. We report on XX sex r eversal, a rare sex chromosomal disorder in humans. Materials and Meth ods: Routine amniocentesis revealed an XX fetal karyotype, although at birth the neonate was phenotypically male. Radiographic evaluation sh owed a normal male urethra and the absence of any female internal geni talia. Subsequent molecular analysis with polymerase chain reaction am plified 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 cas es the SRY and ZFY loci are present, presumably on the paternal X chro mosome, as well as a Klinefelter phenotype. These sex reversing transl ocations 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 se en in these apparent microtranslocation cases. Conclusions: These 4 ca ses demonstrate the usefulness of molecular followup of clinically per plexing sexual discordance. We conclude that SRY and ZFY polymerase ch ain reaction amplification studies should be performed when sexual dis crepancies are noted on prenatal ultrasound and karyotype analysis.