Mutations in the chromatin-associated protein ATRX
Mutations in the chromatin-associated protein ATRX
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DOI：
10.1002/humu.20734
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发表时间：
2008-06-01
期刊：
影响因子：
3.9
通讯作者：
Traeger-Synodinos, Joanne
中科院分区：
文献类型：
--
作者：
Gibbons, Richard J.;Wada, Takahito;Traeger-Synodinos, Joanne
ATRX属于SNF2蛋白家族，其中许多已被证明具有染色质重塑活性。编码基因X的体质突变可引起α -地中海贫血精神发育迟滞（ATR-X）综合征和各种相关疾病，这些疾病通常与深度发育迟缓、面部畸形、生殖器异常和α -地中海贫血有关。在白血病前期α地中海贫血骨髓增生异常综合征（ATMDS）中观察到获得性ATRX突变。ATRX的突变已被证明会干扰基因表达和DNA甲基化。这是一份127个突变的综合报告，其中32个是首次报道。错义突变集中在两个主要的功能域。截断突变在某种程度上似乎被“拯救”了，因此，大多数（如果不是全部的话）构象ATRX突变似乎都是次异形。
ATRX belongs to the SNF2 family of proteins, many of which have been demonstrated to have chromatin remodeling activity. Constitution mutations in the X,encoded gene give rise to alpha thalassemia mental retardation (ATR-X) syndrome and a variety of related conditions that are often associated with profound developmental delay, facial dysmorphism, genital abnormalities, and alpha thalassemia. Acquired mutations in ATRX are observed in the preleukemic condition alpha thalassemia myelodysplastic syndrome (ATMDS). Mutations in ATRX have been shown to perturb gene expression and DNA methylation. This is a comprehensive report of 127 mutations including 32 reported here for the first time. Missense mutations are shown to cluster in the two main functional domains. The truncating mutations appear to be "rescued" to some degree and so it appears likely that most if not all constitutional ATRX mutations are hypomorphs.