Novel GATAD2B loss-of-function mutations cause intellectual disability in two unrelated cases
Novel GATAD2B loss-of-function mutations cause intellectual disability in two unrelated cases
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DOI：
10.1038/jhg.2016.164
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发表时间：
2017-04-01
影响因子：
3.5
通讯作者：
Wu, Lingqian
中科院分区：
文献类型：
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作者：
Luo, Xiaomei;Zou, Yongyi;Wu, Lingqian
GATA锌指结构域2B(GATAD2B)是甲基-CpG-结合蛋白-1复合体(MECP1)的一个亚基，其功能是去乙酰化甲基化的核小体并降低转录活性。最近，GATAD2B基因被认为是智力障碍(ID)患者的候选基因。在这项研究中，我们通过下一代测序(NGS)在两个无关的ID病例中发现了两个新的GATAD2B杂合移码突变。这两个突变c.80_81insGATGT和c.552_555delGAAA都会导致截短的蛋白质，这可能对神经发育不利。我们进行了Western blotting，观察到与正常对照组相比，目标蛋白减少了。这是首次在中国ID患者中发现GATAD2B。我们的发现将拓宽GATAD2B突变的范围，并促进基因诊断和咨询。
GATA zinc finger domain-containing 2B (GATAD2B) is a subunit of the methyl-CpG-binding protein-1 complex (MECP1), which deacetylates methylated nucleosomes and regresses transcriptional activity. Recently, GATAD2B has been elucidated as a candidate gene in patients with intellectual disability (ID). In this study, we identified two novel heterozygous frameshift mutations of GATAD2B in two unrelated ID cases through next-generation sequencing (NGS). Both of the mutations c.80_81insGATGT and c. 552_555delGAAA cause truncated proteins that might be detrimental to neurodevelopment. We performed western blotting and observed a reduction in the target protein compared with normal controls. This is the first report of GATAD2B in Chinese ID patients. Our findings will broaden the spectrum of GATAD2B mutations and facilitate genetic diagnosis and counseling.