Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2811745 | The American Journal of Human Genetics | 2008 | 9 Pages |
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-dependant inhibition of β-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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Authors
Hannah Mandel, Revital Shemer, Zvi U. Borochowitz, Marina Okopnik, Carlos Knopf, Margarita Indelman, Arie Drugan, Dov Tiosano, Ruth Gershoni-Baruch, Mordechai Choder, Eli Sprecher,