A novel missense mutation in hsd17b3 gene in two 46,xy siblings with female external gelitalia

Objective: deficiency of 17β-hydroxysteroid dehydrogenase type 3 (17β-hsd3),which catalyzes the synthesis of testosterone from δ4-androstenedione and is encoded by hsd17b3,is a rare cause of 46,xy disorders of sex development (dsd). up to now,over 30 mutations in hsd17b3 have been reported. to report two siblings with a novel mutation in hsd17b3 gene leading to 17β-hsd3 deficiency. case: a 15-year-old female patient was referred because of primary amenorrhea and signs of virilization. the chromosome analysis showed a 46,xy karyotype. hormonal evaluation revealed a high δ4-androstenedione level with a low serum testosterone/androstenedione (t/a) ratio. a homozygous missense mutation in hsd17b3 resulting in a premature stop codon (p.y287) was found. gonadectomy was performed after the molecular diagnosis and estrogen replacement therapy was initiated. screening of relevant mutation was performed in remaining family members. the father,mother,and a sibling were heterozygous,while a 12-year-old sibling who was raised as a female was homozygous for the same mutation. her karyotype was 46,xy as well. hormonal evaluation revealed a high δ4-androstenedione level with a low serum t/a ratio. gonadectomy was performed and estrogen replacement therapy was initiated consequently. conclusion: we emphasize that 17β-hsd3 deficiency should be considered in virilized female patients at puberty if the t/a ratio is less than 0.8 and the molecular analysis should be performed in both index case and the family members for precise diagnosis and genetic counselling. © 2016,galenos yayincilik. all rights reserved.