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 complet e androgen insensitivity syndrome and to determine whether single-stra nded conformation polymorphism (SSCP) can be used to detect subtle mut ations in the androgen receptor (AR) gene. Design: Amplification, subc loning where appropriate, and sequencing of the AR gene in members of the affected family and to use SSCP to differentiate rapidly mutant fr om normal alleles. Setting: Reproductive endocrinology clinic and labo ratory in a university hospital. Patients: A family of which two siste rs (46 XY) have complete androgen insensitivity syndrome. Results: A n ovel 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 dem onstrated to be the heterozygous carrier of this mutation while the ot her two males in the family carried the normal allele. Single-stranded conformation polymorphism proved useful for defining the normal, muta nt, and heterozygous carrier status of each member of this family. Con clusions: This new mutation of the human AR gene illustrates the impor tance of exon G in receptor function. Single-stranded conformation pol ymorphism is a simple and rapid screening technique that can be used t o detect unknown subtle mutations in the AR gene.