Molecular genetics and pathophysiology of 17β-hydroxysteroid dehydrogenase 3 deficiency

Stefan Andersson, Wayne M. Geissler, Ling Wu, Daphne L. Davis, Melvin M. Grumbach, Maria I. New, Hans P. Schwarz, Sandra L. Blethen, Berenice B. Mendonca, Walter Bloise, Selma F. Witchel, Gordon B. Cutler, Jim Griffin III, Jean D. Wilson, David W Russell

Research output: Contribution to journalArticlepeer-review

193 Scopus citations


Autosomal recessive mutations in the 17β-hydroxysteroid dehydrogenase 3 gene impair the formation of testosterone in the fetal testis and give rise to genetic males with female external genitalia. Such individuals are usually raised as females, but virilize at the time of expected puberty as the result of increases in serum testosterone. Here we describe mutations in 12 additional subjects/families with this disorder. The 14 mutations characterized to date include 10 missense mutations, 3 splice junction abnormalities, and 1 small deletion that results in a frame shift. Three of these mutations have occurred in more than 1 family. Complementary DNAs incorporating 9 of the 10 missense mutations have been constructed and expressed in reporter cells; 8 of the 9 missense mutations cause almost complete loss of enzymatic activity. In 2 subjects with loss of function, missense mutations testosterone levels in testicular venous blood were very low. Considered together, these findings strongly suggest that the common mechanism for testosterone formation in postpubertal subjects with this disorder is the conversion of circulating androstenedione to testosterone by one or more of the unaffected 17β-hydroxysteroid dehydrogenase isoenzymes.

Original languageEnglish (US)
Pages (from-to)130-136
Number of pages7
JournalJournal of Clinical Endocrinology and Metabolism
Issue number1
StatePublished - 1996

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'Molecular genetics and pathophysiology of 17β-hydroxysteroid dehydrogenase 3 deficiency'. Together they form a unique fingerprint.

Cite this