Functional analysis of mutations in TGIF associated with holoprosencephaly
Functional analysis of mutations in TGIF associated with holoprosencephaly
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DOI：
10.1016/j.ymgme.2006.07.011
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发表时间：
2007-01-01
影响因子：
3.8
通讯作者：
Muenke, Maximilian
中科院分区：
文献类型：
--
作者：
El-Jaick, Kenia B.;Powers, Shannon E.;Muenke, Maximilian
无前脑畸形(HPE)是人类最常见的前脑和面部结构畸形。我们目前对HPE发病机制的理解试图将已知HPE基因突变所证明的遗传易感性与环境因素的表观遗传影响相结合。在多个人群队列中，人类TGIF基因的突变或缺失与H PE有关。在这里，我们检查了所有以前报道的突变的功能影响，并描述了另外四个变体。在TGIF的11个序列变异中，除了4个外，所有的序列都可以被证明是功能异常的。相反，在相关基因TGIF2中没有检测到潜在的致病序列变化。这些结果为TGIF在HPE中的作用提供了进一步的证据，并证明了对假定的疾病相关等位基因进行功能分析的重要性。由爱思唯尔公司出版。
Holoprosencephaly (HPE) is the most common structural malformation of the forebrain and face in humans. Our current understanding of the pathogenesis of HPE attempts to integrate genetic susceptibility, evidenced by mutations in the known HPE genes, with the epigenetic influence of environmental factors. Mutations or deletions of the human TGIF gene have been associated with H PE in multiple population cohorts. Here we examine the functional effects of all previously reported mutations, and describe four additional variants. Of the eleven sequence variations in TGIF, all but four can be demonstrated to be functionally abnormal. In contrast, no potentially pathogenic sequence alterations were detected in the related gene TGIF2. These results provide further evidence of a role for TGIF in HPE and demonstrate the importance of functional analysis of putative disease-associated alleles. Published by Elsevier Inc.