Androgen insensitivity syndromes (AIS) are due to end-organ resistance to androgenic
steroids in males leading to defective
virilization of the external genitalia. The phenotype encompasses a wide array of
genital ambiguity and may range from completely female to undervirilized but unequivocally male with
infertility. This disorder is caused by mutations of the
androgen receptor and is an X-linked recessive trait. We have studied 47 patients with AIS and have characterized the underlying molecular abnormality in the
androgen receptor gene. Twenty patients had complete AIS and twenty-seven had partial AIS. Of the latter, 11 were of predominantly female phenotypic appearance and gender was assigned accordingly, while 16 were raised as males. Within the group of complete AIS, two patients had gross deletions within the gene, one had a small deletion, and one had an insertion. In the other patients with complete AIS, as well as all individuals with partial AIS, single
nucleotide substitutions within the coding region were detected, each leading to an
amino acid alteration. Seven
codons were involved in more than one mutation in different cases. In addition, in one patient with
spinal and bulbar muscular atrophy, an elongation of a
glutamine-repeat was characterized. We conclude that mutations in the
androgen receptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist.