Background: The androgen receptor A645D mutation has been described in one patient with ambiguous genitalia and one boy with normal phenotype.
Objective: Because of this phenotypic variation, we screened a cohort of men from the general population (n = 293) as well as men with the following disorders of the genital tract for the mutation: men with prostate cancer (n = 89), testicular cancer (n = 87), and infertility (n = 103). We also investigated the influence of the polymorphic CAG and GGN repeats on the phenotypic outcome.
Results: The A645D variant was found in three men from the general population (1.0%). These men did not differ regarding testosterone or LH concentrations, compared with the rest of this population. In addition, two men with prostate cancer (2.3%) and one infertile man (1.0%) presented with the mutation. No statistical differences in frequency were noted between the study groups, and none of these individuals had any genital malformations. All men who presented with the mutation carried an extraordinarily short GGN repeat of 10 base triplets in combination with long CAG repeats of 26-28 (average 27.3). In contrast, men with GGN=10, but CAG less than 26 did not have the A645D mutation. A single-nucleotide polymorphism analysis revealed that the A645D variant has emerged from the most common haplogroup in our population.
Conclusions: We conclude that the A645D mutation, which is present in 1% of the general Swedish population, is linked to GGN10 and long CAG repeats. Its effect on androgen receptor function is currently unknown.