A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader-Willi syndrome
A paternal deletion of MKRN3, MAGEL2 and NDN does not result in Prader-Willi syndrome
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DOI：
10.1038/ejhg.2008.232
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发表时间：
2009-05-01
影响因子：
5.2
通讯作者：
Buiting, Karin
中科院分区：
文献类型：
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作者：
Kanber, Deniz;Giltay, Jacques;Buiting, Karin
Prader-Willi综合征(PWS)是由父亲15号染色体上5-6MbpDe-nevo缺失、母亲单亲15二体或印记缺陷引起的。这三种病变都导致仅在父亲染色体上活跃的印记基因MKRN3、MAGEL2、NDN、C15orf2、SNURF-Snrpn和70多个C/D盒snoRNA基因(SNORD)缺乏表达。这些基因中的任何一个对PWS的贡献尚不清楚，因为到目前为止还没有描述过单个基因突变。我们报告了两例PWS患者，他们在父亲的染色体上有一个不典型的缺失，该缺失不包括MKRN3，MAGEL2和NDN。在其中一例患者中，NDN具有正常的DNA甲基化模式并表达。在另一例患者中，由于45，X，der(X)t(X；15)(q28；q11.2)不平衡易位，这些基因的父系等位基因被删除。这位患者是肥胖和智力低下的，但没有PWS。我们的结论是，MKRN3、MAGEL2和NDN的缺失不足以引起PWS。
The Prader-Willi syndrome (PWS) is caused by a 5-6 Mbp de novo deletion on the paternal chromosome 15, maternal uniparental disomy 15 or an imprinting defect. All three lesions lead to the lack of expression of imprinted genes that are active on the paternal chromosome only: MKRN3, MAGEL2, NDN, C15orf2, SNURF-SNRPN and more than 70 C/D box snoRNA genes (SNORDs). The contribution to PWS of any of these genes is unknown, because no single gene mutation has been described so far. We report on two patients with PWS who have an atypical deletion on the paternal chromosome that does not include MKRN3, MAGEL2 and NDN. In one of these patients, NDN has a normal DNA methylation pattern and is expressed. In another patient, the paternal alleles of these genes are deleted as the result of an unbalanced translocation 45, X, der(X)t(X;15)(q28;q11.2). This patient is obese and mentally retarded, but does not have PWS. We conclude that a deficiency of MKRN3, MAGEL2 and NDN is not sufficient to cause PWS.