title: 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.
authors.affiliation: Metabolic Disease Unit, Meyer Children's Hospital, Haifa 31096, Israel.
authors.forename: Hannah
authors.initials: H
authors.lastname: Mandel
authors.forename: Revital
authors.initials: R
authors.lastname: Shemer
authors.forename: Zvi U
authors.initials: ZU
authors.lastname: Borochowitz
authors.forename: Marina
authors.initials: M
authors.lastname: Okopnik
authors.forename: Carlos
authors.initials: C
authors.lastname: Knopf
authors.forename: Margarita
authors.initials: M
authors.lastname: Indelman
authors.forename: Arie
authors.initials: A
authors.lastname: Drugan
authors.forename: Dov
authors.initials: D
authors.lastname: Tiosano
authors.forename: Ruth
authors.initials: R
authors.lastname: Gershoni-Baruch
authors.forename: Mordechai
authors.initials: M
authors.lastname: Choder
authors.forename: Eli
authors.initials: E
authors.lastname: Sprecher
mesh_terms: 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
chemical_list: D013256:Steroids; C555581:WNT4 protein, human; D051153:Wnt Proteins; D060528:Wnt4 Protein