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 defectiveandrogen receptor protein due to a mutation of the androgen receptor gene. this prevents normal androgen actionand thus leads to impaired virilization. a point mutation of the androgen receptor gene affecting two siblings withcomplete 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. theandrogen receptor gene was screened for mutations using an automated sequence analyzer (abi prism 310). both girlspossess one substitutions (g>a at position 2086 in exon 4), leading to d695n mutation. mother was found to be a heterozygouscarrier 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 containedpalpable gonads measuring 1.5 cm in largest diameter. ultrasound examination of the pelvis revealed absence of theuterus.serum follicle stimulating hormone (fsh), luteinizing hormone (lh), and testosterone values were higher than normalrange.to our knowledge this is the first confirmed instance of ais due to an ar mutation occurring in familial cases in thiscountry. furthermore, the phenotype has complete association with this mutation.