Complete androgen insensitivity due to a splice-site mutation in the androgen receptor gene and genetic screening with single-stranded conformation polymorphism.

Objective: To characterize the genetic defect in a family with complete androgen insensitivity syndrome and to determine whether single-stranded conformation polymorphism (SSCP) can be used to detect subtle mutations in the androgen receptor (AR) gene.

Design: Amplification, subcloning where appropriate, and sequencing of the AR gene in members of the affected family and to use SSCP to differentiate rapidly mutant from normal alleles.

Setting: Reproductive endocrinology clinic and laboratory in a university hospital.

Patients: A family of which two sisters (46XY) have complete androgen insensitivity syndrome.

Results: A novel single base (G --> A) mutation in the exon G-intron 7 junction of the AR gene caused an abnormal donor splice site leading to complete androgen insensitivity in both affected siblings. Their mother was demonstrated to be the heterozygous carrier of this mutation while the other two males in the family carried the normal allele. Single-stranded conformation polymorphism proved useful for defining the normal, mutant, and heterozygous carrier status of each member of this family.

Conclusions: This new mutation of the human AR gene illustrates the importance of exon G in receptor function. Single-stranded conformation polymorphism is a simple and rapid screening technique that can be used to detect unknown subtle mutations in the AR gene.