Sequence variants in ESR1 and OXTR are associated with Mayer-Rokitansky-Küster-Hauser syndrome

Acta Obstet Gynecol Scand. 2017 Nov;96(11):1338-1346. doi: 10.1111/aogs.13202. Epub 2017 Sep 21.


Introduction: Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus and the upper two-thirds of the vagina in otherwise phenotypically normal females. It is found isolated or associated with renal, skeletal and other malformations. Despite ongoing research, the etiology is mainly unknown. For a long time, the hypothesis of deficient hormone receptors as the cause for MRKHS has existed, supported by previous findings of our group. The aim of the present study was to identify unknown genetic causes for MRKHS and to compare them with data banks including a review of the literature.

Material and methods: DNA sequence analysis of the oxytocin receptor (OXTR) and estrogen receptor-1 gene (ESR1) was performed in a group of 93 clinically well-defined patients with uterovaginal aplasia (68 with the isolated form and 25 with associated malformations).

Results: In total, we detected three OXTR variants in 18 MRKHS patients with one leading to a missense mutation, and six ESR1 variants in 21 MRKHS patients, two of these causing amino acid changes and therefore potentially disease.

Conclusions: The identified variants on DNA level might impair receptor function through different molecular mechanisms. Mutations of ESR1 and OXTR are associated with MRKHS. Thus, we consider these genes potential candidates associated with the manifestation of MRKHS.

Keywords: DNA; Mayer-Rokitansky-Küster-Hauser syndrome; estrogen receptor-1; oxytocin receptor; single nucleotide variation.

MeSH terms

  • 46, XX Disorders of Sex Development / genetics*
  • Adolescent
  • Adult
  • Congenital Abnormalities / genetics*
  • Estrogen Receptor alpha / genetics*
  • Female
  • Genetic Variation
  • Humans
  • Middle Aged
  • Mullerian Ducts / abnormalities*
  • Mutation, Missense
  • Receptors, Oxytocin / genetics*
  • Sequence Analysis, DNA


  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Receptors, Oxytocin

Supplementary concepts

  • Mullerian aplasia

Associated data

  • GENBANK/NM_000916.3