Complete Androgen Insensitivity Syndrome in A Black South African Family: A Clinical and Molecular Investigation

Abstract

To present the first report of a clinical and molecular investigation of a black South African family with complete androgen insensitivity syndrome (CAIS). Biochemical and chromosomal analyses were performed. In addition, the molecular study included microsatellite analysis and DNA sequencing. The index case, an unmarried 21-year-old black phenotypic female patient with primary amenorrhea, was identified in the Division of Endocrinology at a tertiary hospital affiliated with the University of the Witwatersrand. A detailed family history identified further potentially affected members (on the basis of primary amenorrhea), who were also included in the study. A total of 13 family members, including 6 affected subjects, were involved in the molecular study. All affected persons had a 46,XY karyotype, female phenotype, and hormonal profiles commensurate with their clinical diagnosis. The androgen receptor gene in an affected patient was examined for mutations by DNA sequencing. Mutation screening was extended to other family members. The genetic basis for CAIS in this large family is the missense mutation, D732Y, in exon 5 of the androgen receptor ligand-binding domain. To our knowledge, this is the first case report of CAIS in South Africa in which molecular genetic techniques were used to substantiate the clinical diagnosis. The findings in this study have implications for genetic counseling in this family.