Mutations in the conserved domain of SRY are uncommon in XY gonadal dysgenesis.
In order to evaluate the role of SRY in the determination of the testis, we sequenced the conserved domain of the SRY gene in 8 patients with 46,XY gonadal dysgenesis and 3 patients with related disorders, and compared our data with those obtained in 6 other similar studies. In our study, a 609-bp fragment of SRY was amplified by the polymerase chain reaction and the internal conserved motif was sequenced. SRY sequences did not differ from those in normal males in any of our patients. Overall, 5 de novo mutations have been identified among 56 patients with sporadic XY gonadal dysgenesis (8.9%), and 2 de novo mutations have been identified among 18 patients with related conditions (11%). The unexpectedly low frequency of mutations within the SRY conserved domain in these patients could be caused by undetected Y-linked mutations outside the conserved domain in regions that control transcription during development (e.g., promoter/enhancer regions) or to downstream mutations in other sex-determining genes that need not map to the Y.
Pivnick
E K
EK
Department of Pediatrics, University of Tennessee, Memphis 38105.
Wachtel
S
S
Woods
D
D
Simpson
J L
JL
Bishop
C E
CE
D000293:Adolescent; D001483:Base Sequence; D002675:Child, Preschool; D017124:Conserved Sequence / Q000235:genetics*; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics*; D012734:Disorders of Sex Development / Q000235:genetics; D005260:Female; D006059:Gonadal Dysgenesis / Q000235:genetics*; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D016133:Polymerase Chain Reaction; D012730:Sex Chromosomes; D012733:Sex Differentiation / Q000235:genetics; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors
D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors