17β-hydroxysteroid dehydrogenase-3 (17βHSD3) deficiency is an autosomal recessive form of male pseudohermaphroditism due to impaired testicular conversion of androstenedione to testosterone. 46,XY homozygotes or compound heterozygotes for mutations of the HSD17B3 gene have testes and normally developed Wolffian duct derivatives, but they present with undervirilization of the external genitalia, which are often female. About twenty different mutations of the 17βHSD3 gene, located on chromosome 9q22, have been described up to now. In the current study, we describe an additional mutation of the HSD17B3 gene in a 36-yrs old Algerian woman. This subject was born with apparently normal female genitalia, from non-consanguineous parents. Breast development occurred at the age of 12 yrs. At the age of 17 yrs, she presented with primary amenorrhea, a clitoris hypertrophy, a blind-ending vagina and bilateral inguinal hernia. The gonads were removed and histological examination concluded to the presence of testis. Karyotype was 46,XY. As an adult, the hormonal biology was not relevant because of the previous bilateral gonadectomy and pelvic ultrasonography showed neither uterus, deferents, nor prostate. The presumed diagnosis of androgen insensitivity syndrome (AIS) was raised but molecular biology showed no mutation of the androgen receptor (AR) gene. We then sequenced the 17βHSD3 gene, and found a homozygous H271R mutation in exon 10, which is for the first time described. The diagnosis of 17βHSD3 deficiency should then be considered in prepubertal or gonadectomized patients with male pseudohermaphroditism in the absence of AR mutation because it is clinically indistinguishable from AIS. Functional studies of this new mutation are under current evaluation.
01 - 05 Apr 2006
European Society of Endocrinology