在一对同卵双胞胎中，其中一个患有尾端重复畸形，其AXIN1基因的DNA甲基化增加。
Increased DNA methylation at the AXIN1 gene in a monozygotic twin from a pair discordant for a caudal duplication anomaly.
作者信息
Oates N A, van Vliet J, Duffy D L, Kroes H Y, Martin N G, Boomsma D I, Campbell M, Coulthard M G, Whitelaw E, Chong S
机构信息
School of Molecular and Microbial Biosciences, University of Sydney, Australia.
出版信息
Am J Hum Genet. 2006 Jul;79(1):155-62. doi: 10.1086/505031. Epub 2006 May 22.
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.
AXIN1基因与尾部重复异常有关。在一对单卵双胎（MZ）中，其中一个患有尾部重复异常，另一个正常，对他们的AXIN1基因编码区进行了测序，但未发现突变。我们采用亚硫酸氢盐测序法，检测了这对双胞胎以及年龄匹配的双胎和单胎对照中AXIN1基因启动子区域的甲基化情况。外周血单个核细胞中启动子区域的甲基化在个体间存在差异，包括MZ双胞胎对。在患尾部重复异常的MZ双胞胎对中，患病双胞胎该区域的甲基化程度显著高于未患病的双胞胎（P <.0001），且显著高于对照组（P =.02）。我们已证实该CpG岛在体外确实起到启动子的作用，且其活性与甲基化程度呈负相关。这一发现提示，AXIN1启动子的高甲基化可能通过尚未明确的机制与该畸形相关。这种情况可能是某些MZ不一致病例的典型代表。
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