title: Involvement of the WNT and FGF signaling pathways in non-isolated anorectal malformations: sequencing analysis of WNT3A, WNT5A, WNT11, DACT1, FGF10, FGFR2 and the T gene.
abstract: Anorectal malformations (ARMs) comprise a broad spectrum of anomalies, including             anal atresia, congenital anal fistula and persistence of the cloaca. Research             suggests that genetic factors play an important role in ARM development. However,             few genetic variants have been identified. Embryogenesis is orchestrated by crosstalk             of the wingless-type MMTV integration site family (WNT) and fibroblast growth             factor (FGF) signaling pathways in a process that involves several intracellular             cascades. Studies in mice have implicated several genes from these pathways in             the etiology of ARMs. We performed sequencing analysis of seven of these previously             reported genes in 78 patients with ARMs occurring within the context of at least             one additional congenital anomaly. No associations were identified with variants             in WNT3A, WNT5A, WNT11, DACT1, FGF10 or the T gene. In the FGFR2 gene, three novel             heterozygous nucleotide substitutions were identified. Further investigations,             including the study of family members, revealed that these variants were not causally             related to the phenotype in the present ARM cohort. Mutations in the seven investigated             genes may nonetheless be a cause of ARMs in rare cases. However, further studies             should consider genes encoding other proteins in the WNT/FGF signaling pathways             as possible candidates.
authors.affiliation: Institute of Human Genetics, University Hospital of Bonn, D-53127                     Bonn, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Draaken
authors.forename: Wiebke
authors.initials: W
authors.lastname: Prins
authors.forename: Claudia
authors.initials: C
authors.lastname: Zeidler
authors.forename: Alina
authors.initials: A
authors.lastname: Hilger
authors.forename: Sadaf S
authors.initials: SS
authors.lastname: Mughal
authors.forename: Jeanette
authors.initials: J
authors.lastname: Latus
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Boemers
authors.forename: Dominik
authors.initials: D
authors.lastname: Schmidt
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schmiedeke
authors.forename: Nicole
authors.initials: N
authors.lastname: Spychalski
authors.forename: Enrika
authors.initials: E
authors.lastname: Bartels
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000071056:Anorectal Malformations; D001006:Anus, Imperforate / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005326:Fetal Proteins / Q000235:genetics; D051526:Fibroblast Growth Factor 10 / Q000235:genetics; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D056726:Genetic Association Studies; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics; D060449:Wnt Signaling Pathway; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein / Q000235:genetics; D000098908:Brachyury Protein
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D005326:Fetal Proteins; D051526:Fibroblast Growth Factor 10; D005346:Fibroblast Growth Factors; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D051497:Receptor, Fibroblast Growth Factor, Type 2; D020825:T-Box Domain Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; D000098908:Brachyury Protein; C491683:DACT1 protein, human; C496463:FGF10 protein, human; C555510:WNT3A protein, human; C085389:WNT5A protein, human; C540523:Wnt11 protein, human; C496353:FGFR2 protein, human