Disrupted SOX10 Regulation of GJC2 Transcription Causes Pelizaeus-Merzbacher-Like Disease
Disrupted SOX10 Regulation of GJC2 Transcription Causes Pelizaeus-Merzbacher-Like Disease
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DOI：
10.1002/ana.22022
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发表时间：
2010-08-01
影响因子：
11.2
通讯作者：
Inoue, Ken
中科院分区：
文献类型：
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作者：
Osaka, Hitoshi;Hamanoue, Haruka;Inoue, Ken
间隙连接蛋白 γ-2 基因 GJC2 的突变会导致中枢性髓鞘形成不足疾病； Pelizaeus-Merzbacher 样疾病（PMLD；MIM311601）。使用纯合性作图和位置候选基因方法，我们在轻度 PMLD 患者的 GJC2 启动子内有效的 SOX10 结合位点处鉴定了纯合突变 (c.-167A>G)。从功能上讲，这种突变完全废除了 SOX10 结合并减弱了 GJC2 启动子活性。这些发现不仅表明 SOX10 至 GJC2 的转录失调是 PMLD 的一个原因，而且 GJC2 可能部分负责 SOX10 突变引起的中枢髓鞘形成不足。安神经学 2010；68:250-254
Mutations in the gap junction protein gamma-2 gene, GJC2, cause a central hypomyelinating disorder; Pelizaeus-Merzbacher-like disease (PMLD; MIM311601). Using a homozygosity mapping and positional candidate gene approach, we identified a homozygous mutation (c.-167A>G) within the GJC2 promoter at a potent SOX10 binding site in a patient with mild PMLD. Functionally, this mutation completely abolished the SOX10 binding and attenuated GJC2 promoter activity. These findings suggest not only that the SOX10-to-GJC2 transcriptional dysregulation is a cause of PMLD, but also that GJC2 may be in part responsible for the central hypomyelination caused by SOX10 mutations. ANN NEUROL 2010;68:250-254