Arch Gynecol Obstet (2004) 269:266–269 DOI 10.1007/s00404-002-0405-5 ORIGINAL ARTICLE G. Fogu · V. Bertini · S. Dessole · P. Bandiera · P. M. Campus · G. Capobianco · R. Sanna · G. Soro · A. Montella Identification of a mutant allele of the androgen receptor gene in a family with androgen insensitivity syndrome: detection of carriers and prenatal diagnosis Received: 8 July 2002 / Accepted: 17 July 2002 / Published online: 31 July 2003  Springer-Verlag 2003 Abstract We report the results of a molecular study of a large family segregating the complete form of the Androgen Insensitivity Syndrome (CAIS) in several family members from three generations. We identified the mutant allele by polymerase chain reaction (PCR) amplification of the short tandem repeat (CAG)n, highly polymorphic in the population, present in the first exon of the androgen receptor (AR) gene. In this family four different alleles were detected and one of these showed a perfect segregation with the disease. This study enabled us to identify the heterozygous females in this family. We think that this simple, indirect test, is also suitable for prenatal diagnosis of Morris’ syndrome when the mother is heterozygous for the size of the short tandem repeat and one affected subject in the family may be studied. Key words Androgen receptor gene · Linkage · Short tandem repeat · Complete androgen insensitivity syndrome Introduction In 1953 John Morris reported a series of 82 individuals who had a female phenotype despite the presence of bilateral testes. In this review the author described the cardinal features of a clinical syndrome known as “Androgen-Insensitivity Syndrome” (AIS), or Morris’ syndrome [16]. The spectrum of phenotypes in this condition ranges from individuals with ambiguous gen- italia or mild hypospadias (partial AIS), to individuals with the complete disorder (CAIS). The main phenotypic characteristics of individuals affected by the complete form of the androgen insensi- tivity syndrome (CAIS) are female external genitalia, a short, blind ending vagina, the absence of Wolffian duct- derived structures like epididymes, vas deferens and seminal vesicles, the absence of a prostate, development of gynecomastia and the absence of pubic and axillary hair [18]. At the time of the puberty, high testosterone levels are found, combined with high levels of luteinizing hormone, indicating a lack of target organ response to androgen hormone. The androgen’s effects are mediated by the androgen receptor (AR), a ligand-dependent transcription factor [1, 5, 23], thus a defective or absent receptor prevent the normal development of both internal and external male structures in 46 XY individuals [17, 25]. The AR is a protein of 110–114 KDa encoded by a single-copy gene located on the X chromosome at Xq11– 12 [10, 22]; mutations in this gene are thus expressed in emizygous (46 XY) individuals and the AIS is so an X- linked disease. A variety of mutations have been reported in the AR gene: single point mutations resulting in amino acid substitution or premature stopcodons, nucleotide G. Fogu Department of Physiological, Biochemical and Cellular Sciences, University of Sassari, Sassari, Italy G. Fogu · P. M. Campus · R. Sanna · G. Soro Centre of Clinical Genetics, University of Sassari, Sassari, Italy V. Bertini Department of Human and Hereditary Pathology, University of Pavia, Pavia, Italy S. Dessole ( ) ) · G. Capobianco Department of Pharmacology, Gynecology and Obstetrics, University of Sassari, Viale San Pietro 12, 07100 Sassari, Italy e-mail: dessole@uniss.it Tel.: +39-79228260 Fax: +39-79228265 P. Bandiera · A. Montella Department of Biomedical Sciences, University of Sassari, Sassari, Italy