SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4

Am J Hum Genet. 2008 Jan;82(1):39-47. doi: 10.1016/j.ajhg.2007.08.005.


The WNT-signaling pathway plays a major role during mammalian embryogenesis. We report a novel autosomal-recessive syndrome that consists of female to male sex reversal and renal, adrenal, and lung dysgenesis and is associated with additional developmental defects. Using a candidate-gene approach, we identified a disease-causing homozygous missense mutation in the human WNT4 gene. The mutation was found to result in markedly reduced WNT4 mRNA levels in vivo and in vitro and to downregulate WNT4-dependent inhibition of beta-catenin degradation. Taken together with previous observations in animal models, the present data attribute a pivotal role to WNT4 signaling during organogenesis in humans.

MeSH terms

  • Abnormalities, Multiple / genetics*
  • DNA Mutational Analysis
  • Female
  • Genes, Recessive
  • Humans
  • Male
  • Mutation, Missense
  • Organogenesis*
  • Steroids / urine
  • Syndrome
  • Wnt Proteins / genetics*
  • Wnt Proteins / metabolism
  • Wnt4 Protein


  • Steroids
  • WNT4 protein, human
  • Wnt Proteins
  • Wnt4 Protein