Sex-reversed phenotype in association with two novel mutations c.2494delA and c.T3004C in the ligand-binding domain of the androgen receptor gene.
OBJECTIVE
To establish the diagnosis of complete androgen insensitivity syndrome (CAIS) in two patients with characteristic clinical and hormonal findings, relative family history in one of them, and unusual Müllerian remnants in the other.


METHODS
Case report.


METHODS
Research laboratory in the Department of Medical Genetics at a university children's hospital.


METHODS
Two patients with 46,XY sex reversal and two maternal aunts of the first patient with the same clinical condition were tested.


METHODS
Bilateral gonadectomy was performed on both patients.


METHODS
Genetic counseling, cancer prophylaxis, hormone substitution therapy.


RESULTS
Molecular analysis revealed two novel mutations, a frameshift familial (c.2494delA) in patient 1 and a missense sporadic (c.T3004C) in patient 2. The c.2494delA mutation was also detected in two of the three affected maternal aunts of patient 1. Patient 2 presents an unusual persistence of Müllerian structures.


CONCLUSIONS
Genetic counseling of potential women carriers of androgen receptor (AR) mutations is crucial for the early diagnosis of the affected offspring. The presence of Müllerian remnants, although rare, should not exclude the diagnosis of CAIS. Both identified mutations are novel and provide further evidence for the correlation between specific AR mutations and phenotype.
Galani
Angeliki
A
Department of Medical Genetics, Athens University School of Medicine, Aghia Sofia Children's Hospital, Athens, Greece. agalani@med.uoa.gr
Sofocleous
Christalena
C
Karahaliou
Feneli
F
Papathanasiou
Asteroula
A
Kitsiou-Tzeli
Sofia
S
Kalpini-Mavrou
Ariadni
A
D000293:Adolescent; D000568:Amenorrhea / Q000235:genetics; D013734:Androgen-Insensitivity Syndrome / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002648:Child; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006061:Gonadal Dysgenesis, 46,XY / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006552:Hernia, Inguinal / Q000235:genetics; D006801:Humans; D008297:Male; D009095:Mullerian Ducts / Q000002:abnormalities; D020125:Mutation, Missense; D010375:Pedigree; D010641:Phenotype; D011944:Receptors, Androgen / Q000235:genetics*
C410798:AR protein, human; D011944:Receptors, Androgen