Phenotypic heterogeneity associated with identical mutations in residue 870 of the androgen receptor.
OBJECTIVE
Mutations in the androgen receptor (AR) gene result in an X-linked recessive form of male pseudohermaphroditism known as the androgen-insensitivity syndrome (AIS). The alterations most frequently observed are missense or nonsense point mutations in exons 4-8 of the AR gene that affect the steroid-binding domain of the receptor in subjects with various degrees of androgen resistance. Despite the increasing number of AR mutations identified, a reliable genotype-phenotype correlation has not been established and individuals with the same molecular defect may exhibit different phenotypes. Here, we studied a patients with an AIS characterized by bilateral gynecomastia, normal male external genitalia, and normal sperm counts.


METHODS
Exon-specific polymerase chain reaction, single-stranded conformational polymorphism, and sequencing analysis of the subject's AR gene were performed in addition to hormone-binding assays in skin fibroblasts from the patient.


RESULTS
A point mutation at codon 870 of the AR, changing alanine to valine, was detected.


CONCLUSIONS
As AR missense mutations changing alanine 870 to valine have been previously described in 3 unrelated patients showing severe AIS phenotypes, we conclude that phenotypic heterogeneity associated to identical mutations in the AR gene is probably due to individual functional differences in AR coregulator molecules.
Zenteno
Juan Carlos
JC
Servicio de Genética, Hospital General de México, Facultad de Medicina, UNAM, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D.F., México. skofman@servidor.unam.mx
Chávez
Bertha
B
Vilchis
Felipe
F
Kofman-Alfaro
Susana
S
D000328:Adult; D000595:Amino Acid Sequence; D003600:Cytosol / Q000378:metabolism; D013196:Dihydrotestosterone / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D018740:Genetic Heterogeneity; D006177:Gynecomastia / Q000235:genetics*; D006801:Humans; D007700:Kinetics; D008297:Male; D010641:Phenotype; D017354:Point Mutation; D011944:Receptors, Androgen / Q000235:genetics*; D012016:Reference Values; D012867:Skin / Q000166:cytology / Q000473:pathology; D013076:Sperm Count
D011944:Receptors, Androgen; D013196:Dihydrotestosterone