A Novel mutation in peripheral leukocyte androgen receptor in Partial Androgen Insensitivity Syndrome (PAIS)

Abstract

The actions of testosterone and DHT are mediated by the intracellular androgen receptor (AR). It is located on the long arm of the X-chromosome at Xq11- 12. The external genitalia in individuals with PAIS ranges from ambiguous genitalia with hypospadias at birth and gynecomastia at puberty to milder forms with apparent normal phenotype, but infertile male. Urogenital tract ranges from testes that may be cryptorchid over Wolffian duct derivates emptying into the vagina to scrotal testes and normal Wolffian ducts. This is a case report of a 14.5 years old male adolescent which was referred to Institute of Endocrinology due to gynecomastia and female body proportions. Height 170 cm (+0.26 SD), weight 53.6 kg. Breast development was B3–4 and there was no axillary hair, but pubic hair according to Tanner stage P3. Bone age was 14 years (Greulich and Pyle). The subject had male external genitalia with scrotal testes of 10 ml in size. Varicocele was palpated round the upper pole of the left testis. Analysis of sex chromatin: 4/500 neutrophils revealed that the karyotype was 46,XY. Hormones: PRL 684 pmol/l, FSH 1.37 IU/l, LH 12.25 IU/l, E2 0.08 nmol/l, Testosterone 51.7 nmol/l. and 24.4 nmol/l when repeated. Sequence analysis of the AR revealed a CC to TT transition in codon 865 of Exon 7, predicting a Ser to Phe substitution. This mutation has not previously been described. Mastectomy and sclerotherapy of the left testicular vein has been performed. We think testis biopsy is mandatory in early adulthood, due to the increased risk of testis cancer.