Human Molecular Genetics

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© 1992 Oxford University Press

RESEARCH-ARTICLE

Androgen receptor gene mutations identified by SSCP in fourteen subjects with androgen insensitivity syndrome

J. A. Batch⁺, D. M. Williams, H. R. Davies, B. D. Brown, B. A. J. Evans¹, I. A. Hughes and M. N. Patterson^*

Department of Paediatrics, University of Cambridge, Addenbrooke's Hospital Hills Road, Cambridge CB2 2QQ, UK ¹Department of Child Health, University of Wales College of Medicine Heath Park, Cardiff CF4 4XN, UK

^*To whom correspondence should be addresses

Received July 9, 1992; Revised August 17, 1992; Accepted August 17, 1992

The androgen insensitivity syndrome (AIS) is a disorder of male sexual development resulting in a wide range of clinical phenotypes. AIS is classified into two phenotypic forms: complete (CAIS) and partial (PAIS). To determine the molecular basis of the phenotypic diversity in AIS, we have studied 27 subjects (13 CAIS, 14 PAIS), spanning the full range of AIS phenotypes. We report the results of a mutation screen of the androgen receptor gene. The coding regions of the gene were amplified by the polymerase chain reaction and screened for single strand conformation polymorphisms to identify mutations. This was followed by DNA sequencing of putative mutant segments. Androgen receptor gene mutations were identified in nine CAIS and five PAIS subjects. Two of the CAIS mutations in exon A resulted in frameshifts. A third CAIS mutation resulted in the deletion of a single amino acid from the ligand binding domain of the receptor. All other mutations caused single amino acid substitutions in the ligand binding domain. These results suggest that mutations affecting the ligand binding domain of the androgen receptor are the most frequent cause of AIS, although some cases of PAIS may be the result of other, as yet undefined, genetic lesions.

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⁺Present address: Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Flemington Road, Parkille, Melbourne 3052, Australia

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