Substitution mutation C268Y causes 17 beta-hydroxysteroid dehydrogenase 3 deficiency

The 17 beta -hydroxysteroid dehydrogenase (HSD) type 3 isozyme catalyzes th e conversion of androstenedione to testosterone in the testis. Deleterious mutations in the HSD17B3 gene cause undermasculinization in genetic males a ttributable to impaired testosterone biosynthesis. Hence, a hallmark of thi s autosomal recessive disorder is a decreased plasma testosterone-to-andros tenedione ratio. Here, a novel C268Y substitution mutation in exon 10 of th e HSD17B3 gene, in a subject with 17 beta -HSD 3 deficiency, is reported. R econstitution experiments with recombinant protein reveal that substitution of tyrosine for cysteine at position 268 of 17 beta -HSD type 3 abrogates the enzymatic activity. This finding brings to 20 the number of mutations i n the HSD17B3 gene that cause male undermasculinization.