Complete androgen insensitivity syndrome in a black South African family: a clinical and molecular investigation.
OBJECTIVE
To present the first report of a clinical and molecular investigation of a black South African family with complete androgen insensitivity syndrome (CAIS).


METHODS
Biochemical and chromosomal analyses were performed. In addition, the molecular study included microsatellite analysis and DNA sequencing.


RESULTS
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.


CONCLUSIONS
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.
Scott
Emma C
EC
Department of Internal Medicine, Chris Hani Baragwanath Hospital and University of the Witwatersrand, Johannesburg, South Africa.
Greenberg
Tarryn S
TS
Arndt
Silke
S
Ramsay
Michele
M
Shires
Roy
R
D000293:Adolescent; D000328:Adult; D000568:Amenorrhea / Q000175:diagnosis / Q000235:genetics; D013734:Androgen-Insensitivity Syndrome / Q000175:diagnosis* / Q000235:genetics; D044383:Black People / Q000235:genetics; D002871:Chromosome Banding; D004252:DNA Mutational Analysis; D004958:Estradiol / Q000097:blood; D005192:Family Health; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D011944:Receptors, Androgen / Q000235:genetics; D013019:South Africa; D013739:Testosterone / Q000097:blood
D011944:Receptors, Androgen; D013739:Testosterone; D004958:Estradiol; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone