De novo mutations of SETBP1 cause Schinzel-Giedion syndrome
De novo mutations of SETBP1 cause Schinzel-Giedion syndrome
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DOI：
10.1038/ng.581
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发表时间：
2010-06-01
期刊：
影响因子：
30.8
通讯作者：
Veltman, Joris A.
中科院分区：
文献类型：
--
作者：
Hoischen, Alexander;van Bon, Bregje W. M.;Veltman, Joris A.
Schinzel-Giedion综合征的特征是严重的智力迟钝、明显的面部特征和多种先天性畸形；大多数受影响的人在10岁之前死亡。我们对四个受影响个体（病例）的外显子组进行了测序，并在所有四个病例中发现了SETBP1的杂合新生变异。我们还通过Sanger测序在另外8个病例中发现了SETBP1突变。所有突变都聚集在一个高度保守的11bp外显子区域，表明存在显性负性或功能获得效应。
Schinzel-Giedion syndrome is characterized by severe mental retardation, distinctive facial features and multiple congenital malformations; most affected individuals die before the age of ten. We sequenced the exomes of four affected individuals (cases) and found heterozygous de novo variants in SETBP1 in all four. We also identified SETBP1 mutations in eight additional cases using Sanger sequencing. All mutations clustered to a highly conserved 11-bp exonic region, suggesting a dominant-negative or gain-of-function effect.