title: Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly.
abstract: The AXIN1 gene has been implicated in caudal duplication anomalies. Its coding region was sequenced in both members of a monozygotic (MZ) twin pair discordant for a caudal duplication anomaly, but no mutation was found. Using bisulfite sequencing, we examined methylation at the promoter region of the AXIN1 gene in these twins and in twin and age-matched singleton controls. Methylation of the promoter region in peripheral blood mononucleated cells was variable among individuals, including MZ pairs. In the MZ pair discordant for the caudal duplication, this region of the affected twin was significantly more methylated than that of the unaffected twin (P < .0001), which was significantly more methylated than those of the controls (P = .02). We have confirmed that this CpG island does function as a promoter in vitro and that its activity is inversely proportional to the extent of methylation. This finding raises the possibility that hypermethylation of the AXIN1 promoter, by mechanisms as yet undetermined, is associated with the malformation. This case may be paradigmatic for some cases of MZ discordance.
authors.affiliation: School of Molecular and Microbial Biosciences, University of Sydney, Australia.
authors.forename: N A
authors.initials: NA
authors.lastname: Oates
authors.forename: J
authors.initials: J
authors.lastname: van Vliet
authors.forename: D L
authors.initials: DL
authors.lastname: Duffy
authors.forename: H Y
authors.initials: HY
authors.lastname: Kroes
authors.forename: N G
authors.initials: NG
authors.lastname: Martin
authors.forename: D I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: M
authors.initials: M
authors.lastname: Campbell
authors.forename: M G
authors.initials: MG
authors.lastname: Coulthard
authors.forename: E
authors.initials: E
authors.lastname: Whitelaw
authors.forename: S
authors.initials: S
authors.lastname: Chong
mesh_terms: D060466:Axin Protein; D001483:Base Sequence; D002420:Cauda Equina / Q000002:abnormalities*; D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D006801:Humans; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000235:genetics*; D014430:Twins, Monozygotic
chemical_list: C555451:AXIN1 protein, human; D060466:Axin Protein; D017931:DNA Primers; D012097:Repressor Proteins