THE CLINICAL AND MOLECULAR-SPECTRUM OF ANDROGEN INSENSITIVITY SYNDROMES

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 geni tal ambiguity and may range from completely female to undervirilized b ut unequivocally male with infertility. This disorder is caused by mut ations of the androgen receptor and is an X-linked recessive trait. We have studied 47 patients with AIS and have characterized the underlyi ng molecular abnormality in the androgen receptor gene. Twenty patient s had complete AIS and twenty-seven had partial AIS. Of the latter, 11 were of predominantly female phenotypic appearance and gender was ass igned accordingly, while 16 were raised as males. Within the group of complete AIS, two patients had gross deletions within the gene, one ha d a small deletion, and one had an insertion. In the other patients wi th complete AIS, as well as all individuals with partial AIS, single n ucleotide substitutions within the coding region were detected, each l eading to an amino acid alteration. Seven codons were involved in more than one mutation in different cases. In addition, in one patient wit h spinal and bulbar muscular atrophy, an elongation of a glutamine-rep eat was characterized. We conclude that mutations in the androgen rece ptor gene may be present throughout the whole coding region. However, our study provides evidence that several mutational hot spots exist. ( C) 1996 Wiley-Liss, Inc.