Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly.
Cumulative ligand activity of NODAL mutations and modifiers are linked to human heart defects and holoprosencephaly.
复制标题
DOI：
10.1016/j.ymgme.2009.05.005
复制
发表时间：
2009-09
影响因子：
3.8
通讯作者：
Muenke, Maximilian
中科院分区：
文献类型：
--
作者：
Roessler, Erich;Pei, Wuhong;Ouspenskaia, Maia V.;Karkera, Jayaprakash D.;Velez, Jorge Ivan;Banerjee-Basu, Sharmilla;Gibney, Gretchen;Lupo, Philip J.;Mitchell, Laura E.;Towbin, Jeffrey A.;Bowers, Peter;Belmont, John W.;Goldmuntz, Elizabeth;Baxevanis, Andreas D.;Feldman, Benjamin;Muenke, Maximilian
模型生物体中与节点样信号的产生或传播干扰相关的旋眼和偏侧表型是导致人类出生缺陷的类似损伤的潜在例子。然而，人们对人类基因突变的类型及其致病组合知之甚少。在这里，我们描述了对一大组患者的人类 NODAL 基因的突变分析，这些患者的表型与 NODAL 配体功能减弱相一致。在患有先天性心脏缺陷 (CHD)、偏侧性异常（例如左右错误表型）和罕见的前脑无裂畸形 (HPE) 的患者中，检测到 NODAL 等位基因的生物活性显着降低。虽然许多 NODAL 变异是家族特异性突变的典型特征，但我们还报告了常见群体变异中活性显着降低的等位基因的存在。我们提出，其中一些常见变异可作为修饰因子，并有助于这些患者的最终表型结果；此外，我们与模型生物中的菌株特异性修饰剂进行了比较，以支持这种解释。
The cyclopic and laterality phenotypes in model organisms linked to disturbances in the generation or propagation of Nodal-like signals are potential examples of similar impairments resulting in birth defects in humans. However, the types of gene mutation(s) and their pathogenetic combinations in humans are poorly understood. Here we describe a mutational analysis of the human NODAL gene in a large panel of patients with phenotypes compatible with diminished NODAL ligand function. Significant reductions in the biological activity of NODAL alleles are detected among patients with congenital heart defects (CHD), laterality anomalies (e.g. left-right mis-specification phenotypes), and only rarely holoprosencephaly (HPE). While many of these NODAL variants are typical for family-specific mutations, we also report the presence of alleles with significantly reduced activity among common population variants. We propose that some of these common variants act as modifiers and contribute to the ultimate phenotypic outcome in these patients; furthermore, we draw parallels with strain-specific modifiers in model organisms to bolster this interpretation.
登录
查看更多内容
影响因子：
64.8
作者：
Brennan, J;Lu, CC;Robertson, EJ
通讯作者：
Robertson, EJ
影响因子：
9.2
作者：
Cole, F;Krauss, RS
通讯作者：
Krauss, RS
影响因子：
2.7
作者：
Andersson, Olov;Reissmann, Eva;Ibanez, Carlos F.
通讯作者：
Ibanez, Carlos F.
影响因子：
--
作者：
Hagos, Engda G.;Dougan, Scott T.
通讯作者：
Dougan, Scott T.
DOI：
10.1002/tera.1420160304
发表时间：
1977-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
MATSUNAGA, E;SHIOTA, K
通讯作者：
SHIOTA, K