Testicular dysgenesis without adrenal insufficiency in a 46,XY patient with a heterozygous inactive mutation of steroidogenic factor-1

Tomonobu Hasegawa, Maki Fukami, Naoko Sato, Noriyuki Katsumata, Goro Sasaki, Keiko Fukutani, Ken Ichirou Morohashi, Tsutomu Ogata

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96 Citations (Scopus)


Steroidogenic factor-1 (SF-1) regulates multiple genes involved in the adrenal and gonadal development and in the biosynthesis of a variety of hormones, including adrenal and gonadal steroids, anti-Mullerian hormone (AMH), and gonadotropins. We identified a novel SF-1 mutation in a 27-yr-old Japanese patient with a 46,XY karyotype. Sequence analysis was performed for all the seven exons of SF-1, revealing a heterozygous single base pair deletion at exon 2 (18delC) that is predicted to cause a frameshift at the sixth codon and resultant termination at the 74th codon. Functional studies showed that the mutation produced no demonstrable protein and had no transcription activity or dominant negative effect. Clinical features included small dysgenetic testes with vasa deferentia and epididymides, absent uterus, blind-ending vagina, clitoromegaly, and psychosexual disturbance. Endocrine studies showed normal adrenal function (cortisol response to ACTH stimulation, 13.4→25.3 μg/dl) and primary hypogonadism (testosterone response to hCG stimulation, 0.57→0.76 ng/ml; gonadotropin responses to GnRH stimulation: LH, 10→59 mIU/ml; FSH, 36→69 mlU/ml), and urinary steroid hormone profile analysis indicated grossly normal steroidogenic enzyme activities. The results suggest that SF-1 haploinsufficiency can selectively impair testicular development and permit the biosynthesis of AMH and testosterone in dysgenetic testes and the production of gonadotropins in pituitary gonadotropes.

Original languageEnglish
Pages (from-to)5930-5935
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Issue number12
Publication statusPublished - 2004 Dec

ASJC Scopus subject areas

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


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