SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4 by Mandel Hannah, Shemer Revital, Borochowitz Zvi U, Okopnik Marina, Knopf Carlos, Indelman Margarita, Drugan Arie, Tiosano Dov, Gershoni-Baruch Ruth, Choder Mordechai, Sprecher Eli in American journal of human genetics (2008). PubMed

Abstract

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.

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