A novel E153X point mutation in the androgen receptor gene in a patient with complete androgen insensitivity syndrome.
OBJECTIVE
To study a 46, XY newborn patient with a phenotype suggestive of an androgen insensitivity syndrome to confirm an anomaly in the AR gene.


METHODS
Genomic DNA from leukocytes was isolated in order to analyze SRY gene by PCR and sequencing of the eight exons of AR gene. Isolation of human Leydig cell mesenchymal precursors from the testis was performed in order to study testosterone production and response to hCG stimulation in culture.


RESULTS
Surgical exploration disclosed two testes, no Wolffian structures and important Müllerian derivatives. The SRY gene was present in peripheral blood leukocytes. Sequencing of the AR gene evidenced a previously unreported G to T transversion in exon 1 that changed the normal glutamine 153 codon to a stop codon. Interstitial cell cultures produced sizable amounts of testosterone and were responsive to hCG stimulation.


CONCLUSIONS
This E153X nonsense point mutation has not been described previously in cases of AIS, and could lead to the synthesis of a short truncated (153 vs 919 residues) non functional AR probably responsible for the phenotype of complete androgen insensitivity syndrome (CAIS).
Copelli
S B
SB
Laboratoire d'Hormonologie, H pital Lapeyronie et INSERM U 439 Pathologie des récepteurs nucléaires, Montpellier-France. copelli@fend.guti.sld.ar
Lumbroso
S
S
Audran
F
F
Pellizzari
E H
EH
Heinrich
J J
JJ
Cigorraga
S B
SB
Sultan
C
C
Chemes
H E
HE
D013734:Androgen-Insensitivity Syndrome / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009687:Nuclear Proteins; D010375:Pedigree; D017354:Point Mutation; D011944:Receptors, Androgen / Q000235:genetics*; D051876:Sex-Determining Region Y Protein; D013737:Testis / Q000473:pathology; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011944:Receptors, Androgen; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D014157:Transcription Factors