Research Papers:

A novel mutation R190H in the AT-hook 1 domain of MeCP2 identified in an atypical Rett syndrome

Xiao Zhou, Yuangao Liao, Miaojing Xu, Zhong Ji, Yunqi Xu, Liang Zhou, Xiaoming Wei, Peiqian Hu, Peng Han, Fanghan Yang, Suyue Pan and Yafang Hu _

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Oncotarget. 2017; 8:82156-82164. https://doi.org/10.18632/oncotarget.18955

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Xiao Zhou1,2, Yuangao Liao1,3, Miaojing Xu1, Zhong Ji1, Yunqi Xu1, Liang Zhou1, Xiaoming Wei4, Peiqian Hu5, Peng Han4, Fanghan Yang2, Suyue Pan1 and Yafang Hu1

1Department of Neurology, Nanfang Hospital, The Southern Medical University, Guangzhou, China

2Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3The First People’s Hospital of Chenzhou, Chenzhou, China

4Beijing Genomics Institute, Shenzhen, China

5Department of Radiology, Nanfang Hospital, The Southern Medical University, Guangzhou, China

Correspondence to:

Yafang Hu, email: [email protected]

Suyue Pan, email: [email protected]

Keywords: AT-hook 1, methylation of histone 3, MECP2, next generation sequencing technology, Rett syndrome

Received: February 15, 2017     Accepted: May 10, 2017     Published: July 28, 2017


Background: Mutations in Methyl-CpG binding protein 2 (MECP2) have been identified as the disease-causing mutations in Rett Syndrome (RTT). However, no mutation in the AT-hook 1 domain of MECP2 has been reported in RTT yet. The function of AT-hook 1 domain of MECP2 has not been described either.

Methods: The clinical and radiological features of a girl with progressive hyperactivity and loss of acquired linguistic and motor functions were presented. Next generation sequencing was used to screen the causative gene. Effect of the mutant protein on histone 3 methylation was assessed in vitro experiment.

Results: The patient was diagnosed with an atypical RTT at the age of nine. Magnetic resonance imaging revealed a loss of whole-brain volume and abnormal myelination. Genetic analysis identified a de novo novel missense mutation of MECP2 (NM_004992, c.570G->A, p.Arg190His). This mutation is located in the AT-hook 1 domain of MeCP2 protein. Overexpression of the mutant MeCP2 in cultured neuroblastoma cells SH-SY5Y revealed increased level of dimethylated histone 3 lysine 9, a transcriptional repressor marker.

Conclusion: A novel missense mutation in AT-hook 1 domain of MeCP2 was identified in a patient with atypical RTT. Clinical data and in vitro experiment result imply that R190H mutation in AT-hook1 may cause dysfunction of MeCP2 and be a pathogenic variant.

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