De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features
De novo mutations in CSNK2A1 are associated with neurodevelopmental abnormalities and dysmorphic features
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DOI：
10.1007/s00439-016-1661-y
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发表时间：
2016-07-01
期刊：
影响因子：
5.3
通讯作者：
Chung, Wendy K.
中科院分区：
文献类型：
--
作者：
Okur, Volkan;Cho, Megan T.;Chung, Wendy K.
全外显子组测序（WES）可用于有效识别与智力残疾等遗传异质性相关的新生遗传变异。我们对4102例(女性1847例；我们报告了5例与发育迟缓、智力残疾、行为问题、神经松弛、语言问题、小头畸形、厚脑回和畸形特征相关的神经发育障碍患者，在这些患者中，我们发现了CSNK2A1（编码CK2 α的基因，CK2蛋白激酶的催化亚基）的新生错义和典型剪接位点突变。一种普遍存在的丝氨酸/苏氨酸激酶，由两个调节（β）和两个催化（α和/或α '）亚基组成CSNK2A1的体细胞突变与多种癌症有关；然而，这是第一个描述与任何CK2亚基种系突变相关的人类疾病的研究。
Whole exome sequencing (WES) can be used to efficiently identify de novo genetic variants associated with genetically heterogeneous conditions including intellectual disabilities. We have performed WES for 4102 (1847 female; 2255 male) intellectual disability/developmental delay cases and we report five patients with a neurodevelopmental disorder associated with developmental delay, intellectual disability, behavioral problems, hypotonia, speech problems, microcephaly, pachygyria and dysmorphic features in whom we have identified de novo missense and canonical splice site mutations in CSNK2A1, the gene encoding CK2 alpha, the catalytic subunit of protein kinase CK2, a ubiquitous serine/threonine kinase composed of two regulatory (beta) and two catalytic (alpha and/or alpha') subunits. Somatic mutations in CSNK2A1 have been implicated in various cancers; however, this is the first study to describe a human condition associated with germline mutations in any of the CK2 subunits.