Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings
Clinical characterisation of the multiple maternal hypomethylation syndrome in siblings
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DOI：
10.1038/sj.ejhg.5201993
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发表时间：
2008-04-01
影响因子：
5.2
通讯作者：
Hahnemann, Johanne M. D.
中科院分区：
文献类型：
--
作者：
Boonen, Susanne E.;Poerksen, Sven;Hahnemann, Johanne M. D.
我们提出了第一个临床报告的同胞与多母亲低甲基化综合征。两姐妹篇都患有短暂性新生儿糖尿病（TNDM）。通过亚硫酸氢盐处理的DNA的甲基化特异性PCR，我们在两个同胞中的以下母系甲基化位点发现了低甲基化的嵌合谱：ZAC（6 q24），KCNQ 1 OT 1（11p15.5），GRB 10（7p11.2-12），PEG 3（19 q13），PEG 1/MEST（7 q32）和NESPAS（20 q13）。虽然姐姐有一个温和的表型，年轻的一个是重病，并在11个月大时死亡。尽管存在表型差异，但姐妹篇有几种共同的TNDM和BWS表现。这个家族的血缘关系非常密切，父母是堂兄弟姐妹。我们认为，在这个家庭的遗传缺陷是一种新的，最有可能的常染色体隐性缺陷的甲基化机制，无论是在姐妹篇或在他们的母亲，影响她的卵母细胞印迹。复发与受影响的同胞在这个家庭报告的遗传咨询的影响。
We present the first clinical report of sibs with the multiple maternal hypomethylation syndrome. Both sisters presented with transient neonatal diabetes mellitus (TNDM). By methylation-specific PCR of bisulphite-treated DNA, we found a mosaic spectrum of hypomethylation at the following maternally methylated loci in both sibs: ZAC (6q24), KCNQ1OT1 (11p15.5), GRB10 (7p11.2-12), PEG3 (19q13), PEG1/MEST (7q32), and NESPAS (20q13). While the older sister has a milder phenotype, the younger one was severely ill and died at 11 months of age. Despite phenotypic differences, the sisters had several manifestations of both TNDM and BWS in common. The family is highly consanguineous, and the parents are first cousins. We suggest that the genetic defect in this family is a novel, most likely autosomal recessive defect of methylation mechanisms, either in the sisters or in their mother, affecting her oocyte imprinting. The recurrence with affected sibs as reported in this family has implications for genetic counselling.