Molecular genetics and pathophysiology of 17 beta-hydroxysteroid dehydrogenase 3 deficiency.

17β-hydroxysteroid dehydrogenase 3 deficiency in a male pseudohermaphrodite

“…A molecular basis of this disorder has been shown to be the result of any of twenty mutations in the HSD17B3 gene, a gene that appears to be expressed predominately or exclusively in the testes (7,9). The majority of these mutations have been reconstituted by transient expression in cultured cells, and their functional consequences determined (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

“…The purified DNA was then used as a template in PCR using oligonucleotide pairs and PCR conditions as described by Andersson et al (7). The nucleotide sequence of the 11 exons including splice junctions were determined by cycle sequencing using a thermostable DNA polymerase.…”

“…To date, a total of 20 mutations of the HSD17B3 gene have been identified, including sixteen missense mutations, three splice junction abnormalities, and one small deletion that results in a frame shift mutation. Genetically, patients can be homozygous or compound heterozygous (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

The molecular basis of male sexual differentiation

“…At least five different isoenzymes of 17b-HSD exist (35). Only mutations in the type 3 enzyme have been demonstrated to be responsible for defective sex differentiation in patients with 17b-HSD deficiency (36)(37)(38)(39). This disorder is characterised by a severe virilisation defect in 46,XY individuals who, however, show strong signs of virilisation during puberty with marked phallic enlargement (36).…”

“…The 17b-HSD 3-gene is located on chromosome 9p22, spanning over 11 exons and encoding a protein of 310 amino acids. To date, 17 different mutations have been described in the 17b-HSD 3-gene, in association with the clinical findings of 17b-HSD deficiency (36)(37)(38)(39)(40)(41)(42). This enzyme is expressed only in the testes, compatible with its important role in testicular androgen formation.…”