Due to an increased basal serum ratio of androstenedione/testosterone, 17 beta-hydroxysteroid dehydrogenase type 3 (17 beta-HSD 3) deficiency was initially suspected.
Mutations in the HSD17B3 gene causing 17β-HSD3 deficiency are responsible for a rare recessive form of 46, XY Disorders of Sex Development (46, XY DSD).
Mutations in the HSD17B3 gene are associated with a rare form of 46,XY disorder of sex development referred to as 17betaHSD3 deficiency (or as 17-ketosteroid reductase deficiency), due to impaired testicular conversion of Delta4-A into T. 46,XY patients with 17betaHSD3 deficiency are usually classified as female at birth, raised as such, but develop secondary male features at puberty.
The novel large duplication spanning exons 3-10 of the HSD17B3 gene that we report here in compound heterozygosity with the known p.R80Q leads to 17β-HSD-3 deficiency presenting as 46,XY Disorder of Sex Development.
This study aimed at the detection of HSD17B3 gene mutations in Egyptian patients with suspected diagnosis of 46,XY DSD due to 17-β-HSD-3 deficiency and at evaluation of phenotype/genotype relationship of these mutations.
These novel mutations may expand the mutation database of HSD17B3 gene and provide us new insights into the molecular mechanism of 17β-HSD3 deficiency.
Because of a low T/Δ4 ratio after a human chorionic gonadotropin stimulation test, a tentative diagnosis of 17βHSD-3 deficiency was made which was confirmed after genetic analysis of the HSD17B3 gene of the patient.
17Beta-hydroxysteroid dehydrogenase-3 deficiency: diagnosis, phenotypic variability, population genetics, and worldwide distribution of ancient and de novo mutations.