A Case of Wiedemann-Steiner Syndrome Associated with a 46,XY Disorder of Sexual Development and Gonadal Dysgenesis

Sex Dev. 2015;9(5):289-95. doi: 10.1159/000441512. Epub 2015 Nov 7.

Abstract

We report the case of a female patient suffering from a 46,XY disorder of sexual development (DSD) with complete gonadal dysgenesis and Wiedemann-Steiner Syndrome (WDSTS). The coexistence of these 2 conditions has not yet been reported. Using whole exome sequencing and comparative genome hybridization array, we identified a de novo MLL/KMT2A gene nonsense mutation which explains the WDSTS phenotype. In addition, we discovered novel genetic variants, which could explain the testicular dysgenesis observed in the patient, a maternally inherited 167-kb duplication of DAAM2 and MOCS1 genes and a de novo LRRC33/NRROS gene mutation. These genes, some of which are expressed during mouse gonadal development, could be considered as potentially new candidate genes for DSD.

Publication types

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

MeSH terms

  • Codon, Nonsense
  • Craniofacial Abnormalities / genetics
  • Developmental Disabilities / genetics
  • Disorder of Sex Development, 46,XY / genetics*
  • Female
  • Follow-Up Studies
  • Genitalia / pathology
  • Gonadal Dysgenesis, 46,XY / genetics*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Humans
  • Infant, Newborn
  • Malabsorption Syndromes / genetics
  • Male
  • Myeloid-Lymphoid Leukemia Protein / genetics*
  • Pedigree
  • Syndrome

Substances

  • Codon, Nonsense
  • KMT2A protein, human
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase