Androgen receptor gene mutations in 46, XY females

The androgen insensitivity syndrome is a heterogeneous disorder with a wide spectrum of phenotypic abnormalities, ranging from complete female to ambiguous forms that more closely resemble males. The primary abnormality is a defective androgen receptor protein due to a mutation of the androgen receptor gene. This prevents normal androgen action and thus leads to impaired virilization. A point mutation of the androgen receptor gene affecting two siblings with complete androgen insensitivity syndrome is described. On examination they both had normal external female genitalia.Genomic DNA was extracted from EDTA-preserved blood samples and isolated according to standard procedures. The androgen receptor gene was screened for mutations using an automated sequence analyzer (ABI Prism 310). Both girls possess one substitutions (G>A at position 2086 in exon 4), leading to D695N mutation. Mother was found to be a heterozygous carrier for this mutation. GTG banded karyotype of the girls showed they both have male karyotype (46, XY). In addition, the SRY gene screening showed they both have intact SRY gene. The labioscrotal folds contained palpable gonads measuring 1.5 cm in largest diameter. Ultrasound examination of the pelvis revealed absence of the uterus. Serum follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone values were higher than normal range. To our knowledge this is the first confirmed instance of AIS due to an AR mutation occurring in familial cases in this country. Furthermore, the phenotype has complete association with this mutation.