Complete androgen insensitivity syndrome is frequently due to premature stop codons in exon 1 of the androgen receptor gene: an international collaborative report of 13 new mutations.
OBJECTIVE
To confirm the clinical diagnosis of complete androgen insensitivity syndrome (CAIS) by molecular genetic analysis and to determine the prevalence of exon 1 mutations in the androgen receptor (AR) transactivation defects of a large series of CAIS patients.


METHODS
International retrospective study.


METHODS
University Hospital of Montpellier, Department of Hormonology.


METHODS
105 patients with normal female external genitalia, bilateral intra-abdominal or inguinal testis, normal breast development, absent or sparse pubic hair, normal or high endogenous testosterone production, hypoplastic or absent wolffian structures, and 46,XY karyotype.


METHODS
Sequencing of the AR gene.


METHODS
Prevalence of AR exon 1 mutations.


RESULTS
Over a 10-year period (1997 to 2007), we identified 78 AR gene mutations in 105 patients with CAIS; 21 of them were located in exon 1, and 13 of these were new mutations. We report 13 new mutations in the AR gene. All but one were stop codons, and the last was a splicing abnormality.


CONCLUSIONS
The finding that 27% of the mutations in our cohort were localized in exon 1 versus 15% in previous works justifies the sequencing of this exon in patients with CAIS.
Philibert
Pascal
P
Service d'Hormonologie, Hôpital Lapeyronie, CHU de Montpellier, Montpellier, France.
Audran
Françoise
F
Pienkowski
Catherine
C
Morange
Isabelle
I
Kohler
Birgit
B
Flori
Elisabeth
E
Heinrich
Claudine
C
Dacou-Voutetakis
Catherine
C
Joseph
Marie-Geneviève
MG
Guedj
Anne-Marie
AM
Journel
Hubert
H
Hecart-Bruna
Annie-Claude
AC
Khotchali
Ines
I
Ten
Svetlana
S
Bouchard
Philippe
P
Paris
Françoise
F
Sultan
Charles
C
D017398:Alternative Splicing / Q000235:genetics; D013734:Androgen-Insensitivity Syndrome / Q000453:epidemiology* / Q000235:genetics*; D018389:Codon, Nonsense; D015331:Cohort Studies; D003299:Cooperative Behavior; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007391:International Cooperation; D008297:Male; D015995:Prevalence; D011944:Receptors, Androgen / Q000235:genetics*; D012189:Retrospective Studies
D018389:Codon, Nonsense; D011944:Receptors, Androgen