Diagnosis, Phenotypic Variability, Population Genetics, and Worldwide Distribution of Ancient and de Novo Mutations*

17b-Hydroxysteroid dehydrogenase-3 (17bHSD3) deficiency is an autosomal recessive form of male pseudohermaphroditism caused by mutations in the HSD17B3 gene. In a nationwide study on male pseudohermaphroditism among all pediatric endocrinol-ogists and clinical geneticists in The Netherlands, 18 17bHSD3-deficient index cases were identified, 12 of whom initially had received the tentative diagnosis androgen insensitivity syndrome (AIS). The phenotypes and genotypes of these patients were stud-ied. Endocrine diagnostic methods were evaluated in comparison to mutation analysis of the HSD17B3 gene. RT-PCR studies wer