Supplementary Material for: Functional Impact of Novel Androgen Receptor Mutations on the Clinical Manifestation of Androgen Insensitivity Syndrome

Androgens are responsible for the development and maintenance of male
sex characteristics. Dysfunctions in androgen action due to mutations
in the androgen receptor gene (AR) can lead to androgen
insensitivity syndrome (AIS) that can be classified as mild (MAIS),
partial (PAIS), or complete (CAIS). We have analyzed functional effects
of p.Ser760Thr, p.Leu831Phe, p.Ile899Phe, p.Leu769Val, and p.Pro905Arg
mutations and the combination p.Gln799Glu + p.Cys807Phe that were
identified in patients with PAIS or CAIS. The p.Leu769Val and
p.Pro905Arg mutations showed complete disruption of AR action under
physiological hormone concentrations; however, they differed in high DHT
concentrations especially in the N/C terminal interaction assay.
Mutations p.Ser760Thr, p.Leu831Phe, p.Ile899Phe presented
transactivation activities higher than 20% of the wild type in
physiological hormone concentrations and increased with higher DHT
concentrations. However, each one showed a different profile in the N/C
interaction assay. When p.Gln799Glu and p.Cys807Phe were analyzed in
combination, transactivation activities <10% in physiologic hormone
conditions indicated an association with a CAIS phenotype. We conclude
that the functional analysis elucidated the role of mutant ARs, giving
clues for the molecular mechanisms associated with different clinical
AIS manifestations. Differences in hormone-dependent profiles may
provide a basis for the response to treatment in each particular case.