No association between mutations in the human androgen receptor GGN repeat and inter-sex conditions

The functional role of the GGN repeat in the human androgen receptor gene is unknown, although mutations in this region have been found in patients with inter-sex conditions. We have investigated the prevalence of GGN mutations in the androgen receptor in the Swedish population and their relation to male reproductive function. A physical examination and semen analysis was carried out in 223 men under medical examination before military service and in 94 men referred due to infertility and having sperm concentrations <5 x 10(6)/ml. The GGN and CAG repeats in the androgen receptor gene were directly sequenced. Both populations contained two predominant alleles of 23 and 24 GGN repeats, 83.8 and 90.5% respectively. Four mutations, three in the conscripts and one among the infertile men, were found, resulting in three GGC to GGT substitutions and one GGT to GGC substitution. None of the men presented with genital abnormalities, but two conscripts had low ejaculate volumes (0.3 and 0.9 ml). All men carrying a mutation also had GGN lengths >or=24. Three subjects with GGN >24, with no mutations and with normal seminal volumes, were also found. Our findings indicate that point mutations in the GGN repeat are frequently found in the general male population (1.3%; 95% CI: 0.3-3.9%), but are usually not associated with profound changes in the male phenotype.