Paternal somatic and germ-line mosaicism for a sex-determining region on Y (SRY) missense mutation leading to recurrent 46,XY sex reversal

Randall S. Hines, Keith A. Hansen, Sandra P.T. Tho, Iqbal Khan, Yue Y. Zhang, Paul G. McDonough, Leo Plouffe

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Objective: To determine the etiology for recurrent 46,XY sex reversal in a family with two Swyer siblings. Design: Deoxyribonucleic acid (DNA) from peripheral lymphocytes and sperm were analyzed for duplication of the dosage sensitive sex locus (DSS) and for mutations in sex-determining region on Y (SRY). Setting: An academic teaching hospital. Patients: A family consisting of mother, father, and five phenotypic daughters, of which two were 46,XY sex-reversed females. Intervention: Deoxyribonucleic acid (DNA) extraction, polymerase chain reaction (PCR), Southern blotting, dosage densitometry, single-strand conformation polymorphism (SSCP), and sequencing. Main Outcome Measure: Comparison of control and subject DNA. Results: Deoxyribonucleic acid (DNA) analysis of SRY in genomic DNA from the 46,XY sex-reversed siblings revealed identical missense mutations (T → G) in both sisters. Analysis of the SRY gene in paternal lymphocyte and sperm DNA revealed mosaicism for wild and mutant (T → G) SRY sequences. SRY analysis of sperm DNA also demonstrated the same mosaicism for the T → G missense mutation. Conclusion: A postembryonic SRY mutation gave rise to paternal mosaicism for two distinct cell populations (SRY+/SRY-). The presence of a wild type SRY in the somatic cell line may account for a normal pattern of male sexual differentiation, whereas the presence of a mutated SRY in the germ line resulted in two 46,XY sex-reversed offspring. These results confirm a proposed mechanism for the condition of recurrent 46,XY sex-reversed females.

Original languageEnglish (US)
Pages (from-to)675-679
Number of pages5
JournalFertility and sterility
Issue number4
StatePublished - Apr 1997


  • 46,XY sex reversal
  • DNA
  • DSS
  • SRY
  • SSCP
  • Swyer
  • mosaicism

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology


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