SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4.
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.
Mandel
Hannah
H
Metabolic Disease Unit, Meyer Children's Hospital, Haifa 31096, Israel.
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
D000015:Abnormalities, Multiple / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D038081:Organogenesis; D013256:Steroids / Q000652:urine; D013577:Syndrome; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism; D060528:Wnt4 Protein
D013256:Steroids; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein