Partial deletion of DMRT1 causes 46,XY ovotesticular disorder of sexual development

Eur J Endocrinol. 2012 Jul;167(1):119-24. doi: 10.1530/EJE-12-0136. Epub 2012 May 9.

Abstract

Objective: Ovotesticular disorder of sexual development (DSD) is an unusual form of DSD, characterized by the coexistence of testicular and ovarian tissue in the same individual. In a subset of patients, ovotesticular DSD is caused by 46,XX/46,XY chimerism or mosaicism. To date, only a few monogenetic causes are known to be associated with XX and XY ovotesticular DSD.

Design and methods: Clinical, hormonal, and histopathological data, and results of high-resolution array-comparative genomic hybridization (CGH) were obtained from a female patient with 46,XY ovotesticular DSD with testicular tissue on one side and an ovary harboring germ cells on the other. Results obtained by array-CGH were confirmed by RT-quantitative PCR.

Results: We detected a deletion of ∼35 kb affecting exons 3 and 4 of the DMRT1 gene in a female patient with 46,XY ovotesticular DSD. To the best of our knowledge, this is the smallest deletion affecting DMRT1 presented to this point in time.

Conclusions: We suggest that haploinsufficiency of DMRT1 is sufficient for both XY gonadal dysgenesis and XY ovotesticular DSD. Furthermore, array-CGH is a very useful tool in the molecular diagnosis of DSD.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Exons
  • Female
  • Gonadal Dysgenesis, 46,XY / diagnosis
  • Gonadal Dysgenesis, 46,XY / genetics*
  • Haploinsufficiency / genetics*
  • Humans
  • Infant, Newborn
  • Ovotesticular Disorders of Sex Development / diagnosis
  • Ovotesticular Disorders of Sex Development / genetics*
  • Transcription Factors / genetics*

Substances

  • DMRT1 protein
  • Transcription Factors