新功能、新界面、新体验,扫描即可下载生物谷APP!
首页 » 白血病 » Nat Gene:白血病相关的基因突变或影响儿童的机体发育

Nat Gene:白血病相关的基因突变或影响儿童的机体发育

来源:生物谷 2014-03-10 23:26

2014年3月10日 讯 /生物谷BIOON/ --近日,一项刊登在国际杂志Nature Genetics上的研究论文中,来自伦敦癌症研究所的研究人员通过研究发现,和儿童白血病相关的基因突变(DNA甲基转移酶基因突变)或许会影响患者的生长和智力发育,早在之前研究者就发现了DNA甲基转移酶基因(DNMT3A)的突变和儿童白血病相关。

所有的儿童均比其同龄儿童身高高,其具有类似的面部特征以及智力障碍,这些遗传突变并没有在其父母机体中出现,所有儿童的病症均为DNMT3A过度发育综合征;研究者开展这项研究旨在鉴别出引发这些儿童发育障碍的原因,DNMT3A基因对于儿童发育至关重要,因为其可以将甲基标记添加于DNA上从而来确定哪些基因何时处于活性状态。

令研究者感兴趣的是DNMT3A的突变仅仅发生在白血病患儿的机体中,而且在白血病患儿中的突变和在DNMT3A过度发育综合征患者中的突变并不一样。文章中研究者对152个DNMT3A过度发育综合征障碍患儿和其父母进行分析研究发现了一些新型遗传突变,研究者Nazneen Rahman教授表示,DNMT3A突变可以作为一种新型的人类发育障碍的原因,而本文的研究对于揭示患者出现发育障碍的原因也非常关键。

由于突变在儿童机体中出现的比率较高,而且并不是由父母遗传而来,因此家庭中其他儿童的发病风险似乎非常低;研究者希望鉴别出的新型遗传突变为更好地揭示个体发育障碍以及开发新型的疗法提供一定的思路和研究基础。(生物谷Bioon.com)

doi:10.1038/ng.2917
Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability

Katrina Tatton-Brown, Sheila Seal, Elise Ruark, Jenny Harmer, Emma Ramsay, Silvana del Vecchio Duarte, Anna Zachariou, Sandra Hanks, Eleanor O'Brien, Lise Aksglaede, Diana Baralle, Tabib Dabir, Blanca Gener, David Goudie, Tessa Homfray, Ajith Kumar, Daniela T Pilz, Angelo Selicorni, I Karen Temple, Lionel Van Maldergem, Naomi Yachelevich, Childhood Overgrowth Consortium, Robert van Montfort & Nazneen Rahman

Overgrowth disorders are a heterogeneous group of conditions characterized by increased growth parameters and other variable clinical features such as intellectual disability and facial dysmorphism1. To identify new causes of human overgrowth, we performed exome sequencing in ten proband-parent trios and detected two de novo DNMT3A mutations. We identified 11 additional de novo mutations by sequencing DNMT3A in a further 142 individuals with overgrowth. The mutations alter residues in functional DNMT3A domains, and protein modeling suggests that they interfere with domain-domain interactions and histone binding. Similar mutations were not present in 1,000 UK population controls (13/152 cases versus 0/1,000 controls; P < 0.0001). Mutation carriers had a distinctive facial appearance, intellectual disability and greater height. DNMT3A encodes a DNA methyltransferase essential for establishing methylation during embryogenesis and is commonly somatically mutated in acute myeloid leukemia2, 3, 4. Thus, DNMT3A joins an emerging group of epigenetic DNA- and histone-modifying genes associated with both developmental growth disorders and hematological malignancies5.

温馨提示:87%用户都在生物谷APP上阅读,扫描立刻下载! 天天精彩!


相关标签

最新会议 培训班 期刊库