PubMed1995
OBJECTIVE: Androgen insensitivity syndrome is a disorder of male sexual development which results in varying degrees of undervirilization in 46XY individuals with functional testes. In the most severe form, complete androgen insensitivity syndrome (CAIS), patients have a normal female appearance. Although CAIS is not life-threatening, affected individuals are infertile and require counselling, gonadectomy, hormone therapy, and sometimes vaginoplasty. Many families therefore request genetic counselling. Defects in the androgen receptor gene account for most if not all cases of CAIS. The purpose of this study was to evaluate the use of the polyglutamine and polyglycine trinucleotide repeat polymorphisms in the first exon of the androgen receptor gene for carrier status determination in three CAIS families. In two of these families novel mutations in the androgen receptor gene were subsequently identified which allowed confirmation of carrier status and also a prenatal diagnosis to be made in one family. PATIENTS: Three CAIS families were studied. The index cases all presented with a clinical phenotype typical of CAIS. MEASUREMENTS: Family members were typed initially for the polyglutamine repeat. In one family this was not informative and the polyglycine repeat was therefore studied. In this and one further family, the androgen receptor gene was sequenced to identify the mutation causing the CAIS. RESULTS: On the basis of information from trinucleotide repeat analysis carrier status could be assessed in each family. In one family, evidence for somatic instability of the polyglutamine repeat was found. In the same family, a novel mutation in the androgen receptor gene, which substituted valine for leucine 881, was identified. Other family members were subsequently typed for the mutation and a prenatal diagnosis was performed. A novel mutation was also identified in a second family substituting the glycine codon at position 371 with a stop codon. Other family members were typed for this mutation. CONCLUSIONS: Both the polyglutamine and polyglycine repeat polymorphisms are useful for the genetic counselling of complete androgen insensitivity syndrome families. In some cases, however, where the family history is limited, more precise information can be provided only once the androgen receptor mutation causing the complete androgen insensitivity syndrome has been identified.