[Complete androgen insensitivity in an Icelandic family caused by mutation in the steroid binding region of the androgen receptor.].

INTRODUCTION

Androgen insensitivity syndrome (AIS) is a X-linked rescessive disorder characterized by impairment of the androgen-dependant male sexual differentiation. The cause of AIS is in most cases a mutation in the gene of the androgen receptor on the X chromosome. In this study we describe an Icelandic family with two girls with AIS. A search for mutations in the androgen receptor gene was performed in order to identify the genetical and molecular basis for AIS in this family.

MATERIAL AND

METHODS

Genomic DNA was isolated from two girls with complete AIS and their close relatives. PCR was used to amplify all eight exons of the androgen receptor gene of the two AIS girls and SSCP used to screen for mutations. DNA fragments showing abnormal SSCP pattern were subjected to nucleotide sequencing. PCR based diagnostic method was developed and used to detect the mutation causing AIS in the family.

RESULTS AND

CONCLUSIONS

Using SSCP and DNA sequencing a CGA to CAA missense mutation in exon 5 at codon 752 was identified. The mutation causes in an Arg to Gln amino acid substitution (R752Q mutation) in the ligand binding domain of the androgen receptor and a complete androgen insensitivity. Members of the family were genotyped using a PCR based method for identification of the mutant allele. The results strongly indicated a de novo mutation in a germ cell of the maternal grandmother, as the mutation was not found in her blood leucocytes. The diagnostic test provided a basis for genetic counselling for the family.