Mutations and sequence variants in the testis-determining region of the Y chromosome in individuals with a 46,XY female phenotype.
The testis-determining gene SRY (sex determining region, Y) is located on the short arm of the Y chromosome and consists of a single exon, the central third of which is predicted to encode a conserved motif with DNA binding/bending properties. We describe the screening of 26 patients who presented with 46,XY partial or complete gonadal dysgenesis for mutations in both the SRY open reading frame (ORF) and in 3.8 kb of Y-specific flanking sequences. DNA samples were screened by using the fluorescence-assisted mismatch analysis (FAMA) method. In two patients, de novo mutations causing complete gonadal dysgenesis were detected in the SRY ORF. One was a nonsense mutation 5' to the HMG box, whereas the other was a missense substitution located at the C terminus of the conserved motif and identical to one previously detected in an unrelated patient. In addition, two Y-specific polymorphisms were found 5' to the SRY gene, and a sequence variant was identified 3' to the SRY polyadenylation site. No duplications of the DSS region in 20 of these patients were detected.
Veitia
R
R
Unité d'Immunogénétique Humaine, Institut Pasteur, Paris, France.
Ion
A
A
Barbaux
S
S
Jobling
M A
MA
Souleyreau
N
N
Ennis
K
K
Ostrer
H
H
Tosi
M
M
Meo
T
T
Chibani
J
J
Fellous
M
M
McElreavey
K
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D017124:Conserved Sequence; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D005819:Genetic Markers; D006059:Gonadal Dysgenesis / Q000235:genetics*; D006801:Humans; D008297:Male; D009687:Nuclear Proteins; D016366:Open Reading Frames; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D051876:Sex-Determining Region Y Protein; D013737:Testis; D014157:Transcription Factors; D014960:X Chromosome; D014998:Y Chromosome
D017931:DNA Primers; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors