title: Clinical and molecular spectrum of patients with 17β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) deficiency.
abstract: The enzyme 17β-hydroxysteroid dehydrogenase type 3 (17-β-HSD3) catalyzes the conversion of androstenedione to testosterone in the testes, and its deficiency is a rare disorder of sex development in 46,XY individuals. It can lead to a wide range of phenotypic features, with variable hormonal profiles. We report four patients with the 46,XY karyotype and 17-β-HSD3 deficiency, showing different degrees of genital ambiguity, increased androstenedione and decreased testosterone levels, and testosterone to androstenedione ratio < 0.8. In three of the patients, diagnosis was only determined due to the presence of signs of virilization at puberty. All patients had been raised as females, and female gender identity was maintained in all of them. Compound heterozygosis for c.277+2T>G novel mutation, and c.277+4A>T mutation, both located within the intron 3 splice donor site of the HSD17B3 gene, were identified in case 3. In addition, homozygosis for the missense p.Ala203Val, p.Gly289Ser, p.Arg80Gln mutations were found upon HSD17B3 gene sequencing in cases 1, 2, and 4, respectively.
authors.affiliation: Departamento de Pediatria, Faculdade de Ciências Médicas, Universidade Estadual de Campinas, Campinas, SP, Brazil.
authors.forename: Carla Cristina Telles de Sousa
authors.initials: CC
authors.lastname: Castro
authors.forename: Guilherme
authors.initials: G
authors.lastname: Guaragna-Filho
authors.forename: Flavia Leme
authors.initials: FL
authors.lastname: Calais
authors.forename: Fernanda Borchers
authors.initials: FB
authors.lastname: Coeli
authors.forename: Ianik Rafaela Lima
authors.initials: IR
authors.lastname: Leal
authors.forename: Erisvaldo Ferreira
authors.initials: EF
authors.lastname: Cavalcante-Junior
authors.forename: Isabella Lopes
authors.initials: IL
authors.lastname: Monlleó
authors.forename: Silma Regina Ferreira
authors.initials: SR
authors.lastname: Pereira
authors.forename: Roberto Benedito de Paiva E
authors.initials: RB
authors.lastname: Silva
authors.forename: José Roberto Erbolato
authors.initials: JR
authors.lastname: Gabiatti
authors.forename: Antonia Paula
authors.initials: AP
authors.lastname: Marques-de-Faria
authors.forename: Andrea Trevas
authors.initials: AT
authors.lastname: Maciel-Guerra
authors.forename: Maricilda Palandi De
authors.initials: MP
authors.lastname: Mello
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra-Junior
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000172:deficiency* / Q000235:genetics; D000293:Adolescent; D002675:Child, Preschool; D012734:Disorders of Sex Development / Q000201:enzymology* / Q000235:genetics; D005260:Female; D006061:Gonadal Dysgenesis, 46,XY / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*
chemical_list: D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3