MAP3K1-related gonadal dysgenesis: Six new cases and review of the literature

Andrea Granados, Veronica I. Alaniz, Lauren Mohnach, Hayk Barseghyan, Eric Vilain, Harry Ostrer, Elisabeth H. Quint, Ming Chen, Catherine E. Keegan

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


Investigation of disorders of sex development (DSD) has resulted in the discovery of multiple sex-determining genes. MAP3K1 encodes a signal transduction regulator in the sex determination pathway and is emerging as one of the more common genes responsible for 46,XY DSD presenting as complete or partial gonadal dysgenesis. Clinical assessment, endocrine evaluation, and genetic analysis were performed in six individuals from four unrelated families with 46,XY DSD. All six individuals were found to have likely pathogenic MAP3K1 variants. Three of these individuals presented with complete gonadal dysgenesis, characterized by bilateral streak gonads with typical internal and external female genitalia, while the other three presented with partial gonadal dysgenesis, characterized by incomplete testicular development, resulting in clitoral hypertrophy with otherwise typical female external genitalia. Testing for MAP3K1 variants should be considered in patients with 46,XY complete or partial gonadal dysgenesis, particularly in families with multiple members affected with 46,XY DSD. Identification of a MAP3K1 variant should prompt an evaluation for DSD in female siblings of the proband.

Original languageEnglish (US)
Pages (from-to)253-259
Number of pages7
JournalAmerican Journal of Medical Genetics, Part C: Seminars in Medical Genetics
Issue number2
StatePublished - Jun 2017


  • 46,XY DSD
  • MAP3K1
  • disorders of sex development
  • gonadal dysgenesis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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