title: Sequencing of the DKK1 gene in patients with anorectal malformations and hypospadias.
abstract: Anorectal malformations (ARM) are rare congenital malformations of the gastrointestinal tract. Approximately 60% of the patients have additional congenital malformations, such as hypospadias. A recently published article showed that deletion of one single gene, dickkopf WNT signaling pathway inhibitor-1 (Dkk1), resulted in an imperforate anus with rectourinary fistula and preputial hypospadias in mice. To determine whether DKK1 also plays a role in the etiology of ARM and hypospadias in humans, we sequenced the four exons of the DKK1 gene in 17 patients affected with both ARM and hypospadias. No new potential disease-causing variant was identified. However, we detected a known non-synonymous variant in one patient, which was predicted in silico to be damaging, and the corresponding unaffected amino acid is highly conserved.
  
  
  CONCLUSIONS
  In this human study, a potential interesting non-synonymous variant was found in the DKK1 gene. Whether this variant plays a contributory role in the genesis of ARM or hypospadias would require a much larger study.
authors.affiliation: Department for Health Evidence (133), Radboud university medical center, P.O. Box 9101, 6500 HB, Nijmegen, The Netherlands, Romy.vandePutte@radboudumc.nl.
authors.forename: Romy
authors.initials: R
authors.lastname: van de Putte
authors.forename: Charlotte H W
authors.initials: CH
authors.lastname: Wijers
authors.forename: Ivo
authors.initials: I
authors.lastname: de Blaauw
authors.forename: Wout F J
authors.initials: WF
authors.lastname: Feitz
authors.forename: Carlo L M
authors.initials: CL
authors.lastname: Marcelis
authors.forename: Marina
authors.initials: M
authors.lastname: Hakobjan
authors.forename: Cornelius E J
authors.initials: CE
authors.lastname: Sloots
authors.forename: Yolande
authors.initials: Y
authors.lastname: van Bever
authors.forename: Han G
authors.initials: HG
authors.lastname: Brunner
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
authors.forename: Iris A L M
authors.initials: IA
authors.lastname: van Rooij
authors.forename: Loes F M
authors.initials: LF
authors.lastname: van der Zanden
mesh_terms: D000071056:Anorectal Malformations; D001006:Anus, Imperforate / Q000235:genetics*; D004247:DNA / Q000302:isolation & purification; D014644:Genetic Variation; D006801:Humans; D007021:Hypospadias / Q000235:genetics*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA
chemical_list: C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D004247:DNA