title: Investigation of FGF10 as a candidate gene in patients with anorectal malformations and exstrophy of the cloaca.
abstract: The spectrum of anorectal malformations (ARM) comprises anal stenosis, ectopic anus, recto-urogenital fistula, persistent cloaca, multisystem VACTERL (VATER associations including cardiac and limb anomalies) associations, and exstrophy of the cloaca (CE). The latter also constitutes the most severe form of the bladder exstrophy epispadias complex. Since recent data revealed that fibroblast growth factor 10 (fgf-10) invalidation in mice resulted in a genetically reproducible urorectal defect, we considered FGF10 a suitable candidate gene for ARM and CE, as the protein seems to be involved in the development of this primary developmental field. A total of 20 patients (ten with ARM and VACTERL association, respectively, and ten with CE) were analysed for genomic mutations in the coding regions and exon-intron boundaries of FGF10. Aside from a common FGF10 variant no deviation from the wild-type sequence could be detected and data obtained is not supportive of FGF10 as a genetic cause of ARMs or CE in the patients investigated. Nonetheless, mutations in possibly further upstream located promoter regions and/or unknown regulatory sequences or non-coding regions cannot be excluded. Furthermore, it cannot be ruled out that other genes involved in the signalling pathway of FGF10 may contribute to the formation of these congenital malformations.
authors.affiliation: Department of Clinical Chemistry and Pharmacology, University of Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: Victoria
authors.initials: V
authors.lastname: Krüger
authors.forename: Mercedeh
authors.initials: M
authors.lastname: Khoshvaghti
authors.forename: Heiko
authors.initials: H
authors.lastname: Reutter
authors.forename: Hannes
authors.initials: H
authors.lastname: Vogt
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Boemers
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000483:Alleles; D001003:Anal Canal / Q000002:abnormalities; D001746:Bladder Exstrophy / Q000097:blood / Q000235:genetics*; D002988:Cloaca / Q000002:abnormalities; D004247:DNA / Q000235:genetics*; D004065:Digestive System Abnormalities / Q000097:blood / Q000235:genetics*; D051526:Fibroblast Growth Factor 10 / Q000235:genetics*; D005787:Gene Frequency; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D012007:Rectum / Q000002:abnormalities
chemical_list: C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D004247:DNA