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 phenotypic outcome in the case of a 45,X/47,XYY female.


METHODS
Analysis of genomic DNA for mutations in SRY.


METHODS
An academic teaching hospital.


METHODS
A family that included one phenotypic female with 45,X/47,XYY mosaicism.


METHODS
Extraction of DNA, polymerase chain reaction analysis, nucleotide sequencing, and restriction enzyme analysis.


METHODS
Comparison of control and subject DNA sequences.


RESULTS
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 just upstream of a conserved DNA-binding motif. Neither other mutations nor nucleotide mosaicisms were found in the remaining regions of the gene. This mutation was not present in the patient's normal father.


CONCLUSIONS
The mutant SRY may be assumed to induce a nonfunctional SRY-coded protein that lacks a DNA-binding motif. These results explain the phenotypic female and the gonadal dysgenesis in the 45,X/ 47,XYY sex-reversed offspring.
Takagi
A
A
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Imai
A
A
Tamaya
T
T
D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D009030:Mosaicism / Q000235:genetics; D009687:Nuclear Proteins; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors; D014424:Turner Syndrome / Q000235:genetics; D014997:XYY Karyotype / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors