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

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.

SUBMITTER: Mandel H

PROVIDER: S-EPMC2253972 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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

Mandel Hannah H Shemer Revital R Borochowitz Zvi U ZU Okopnik Marina M Knopf Carlos C Indelman Margarita M Drugan Arie A Tiosano Dov D Gershoni-Baruch Ruth R Choder Mordechai M Sprecher Eli E

American journal of human genetics 20080101 1

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- ...[more]

PMID: 18179883

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