A novel sex-determining region on Y (SRY) nonsense mutation identified in a 45,X/47,XYY female

Objective: To determine whether an SRY mutation participated in the phenoty pic outcome in the case of a 45,X/47,XYY female. Design: Analysis of genomic DNA for mutations in SRY. Setting: An academic teaching hospital. Patient(s): A family that included one phenotypic female with 45,X/47,XYY m osaicism. Intervention(s): Extraction of DNA, polymerase chain reaction analysis, nuc leotide sequencing, and restriction enzyme analysis. Main Outcome Measure(s): Comparison of control and subject DNA sequences. Result(s): The patient demonstrated one nucleotide (thymine, T) deletion at position 422, leading to a frame-shift mutation. This mutation changes the codon for Tyr (TAT) to a stop codon (TAG) within the open reading frame ju st upstream of a conserved DNA-binding motif. Neither other mutations nor n ucleotide mosaicisms were found in the remaining regions of the gene. This mutation was not present in the patient's normal father. Conclusion(s): The mutant SRY may be assumed to induce a nonfunctional SRY- coded protein that lacks a DNA-binding motif. These results explain the phe notypic female and the gonadal dysgenesis in the 45,X/47,XYY sex-reversed o ffspring. (Fertil Steril(R) 1999;72:167-9. (C) 1999 by American Society for Reproductive Medicine.)