Testicular Feminization in two Siblings; Is This the Same Mutation?

Objective: Complete form of androgen insensitivity was first described by Morris and Mahesh in 1960s. This X-linked trait occurs in one of 20,000 to 64,000 male births. Androgen receptor gene is located on the short arm of the X chromosome. 200 mutations are known at this locus. External genital tract is phenotypically feminine with short blind vagina. Uterus, often Fallopian tubes, Mϋllerian and Wolffian remnants are absent. End organ insensitivity leads to sparse pubic and axillary hair. Patients often present as adolescent girls with primary amenorrhea and bilateral inguinal hernia.
Case Report: Third offspring of a first cousin marriage was assessed in routine neonatal examination a few hours after birth. Systemic physical examination was normal, external genital tract had normal female appearance. There was a bilateral direct inguinal hernia containing ovoid masses. Karyotype was 46XY. The first offspring was 15 years old and raised as female, with history of bilateral orchiectomy and herniorrhaphy in early infancy. Recent laparoscopy showed that uterus was absent. Karyotype was 46XY. Other sibling was a normal male with 46XY karyotype and coincidental idiopathic nephrocalcinosis. May be these are same mutations on the same gene locus. DNA analysis and sequencing will clear this dilemma.
Conclusion: Ocurrence of androgen insensitivity has been reported in literature for 3 decades. In the recent decade, authors achieved the ability to clarify the mutations completely. DNA sequencing and assessing 5 alpha reductase activity in genital skin fibroblasts in these two siblings is strongly recommended.

Keywords
Androgen insensitivity , CAIS , Iranian siblings , Phenotype , Testicular feminization