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Large De Novo Microdeletion in Epilepsy with Intellectual and Developmental Disabilities, with a Systems Biology Analysis

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Systems Neuroscience

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 21))

Abstract

Epilepsy is one of the most common complex neurological diseases. It is frequently associated with intellectual and developmental disabilities (ID/DD). In recent years, copy number variation (CNV), especially microdeletion, was proven to be a potential key factor of genetic epilepsy. In this paper, the authors tested the hypothesis that the large de novo rare CNV is an important cause of epilepsy with ID/DD. We performed a custom array comparative genomic hybridization (aCGH) to detect the CNVs of 96 Chinese epileptic patients with ID/DD. The aCGH was designed with a higher density probe coverage of 320 genes known to be involved in epilepsy and ID/DD with lower density whole-genome backbone coverage. We detected 9 large de novo rare microdeletions from 8 patients. These CNVs are located on 2q24.1, 2q33.1-q34, 5q13.2 (2 similar CNVs), 5q33.1-q34, 17p13.2, 22q11.21-q11.22 (2 identical CNVs) and Xp22.31. We also found that only a few genes in the CNVs are known epilepsy related genes. By analysis with systems biology, we found most of the genes are interacting genes known to be epilepsy related genes. We also found a gene motif “BGNADP”, constructed by BTD, GALNT10, NMUR2, AUTS2, DLG2 and PTPRD, would be a key motif in epilepsy and ID/DD. These findings strongly indicate that some large de novo rare microdeletion is an important pathological cause of epilepsy with ID/DD. Our study also found a gene motif “BGNADP” should be a key small network in epilepsy with ID/DD.

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Authors and Affiliations

  1. Department of Pediatrics, Peking University First Hospital, Peking University Health Science Center, Beijing, China

    Kai Gao, Yujia Zhang, Weijing Kong, Han Xie, Jingmin Wang, Ye Wu, Xiru Wu, Xiaoyan Liu, Yuehua Zhang & Yuwu Jiang

  2. Institute of Reproduction and Development, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China

    Ling Zhang & Feng Zhang

  3. Laboratory for Functional Study of Astrocytes, Department of Neurobiology, School of Basic Medical Sciences, Key Laboratory for Neuroscience, Ministry of Education, National Health and Family Planning Commission, Neuroscience Research Institute, Peking University, Beijing, China

    Albert Cheung-Hoi Yu

  4. Hai Kang Life Corporation Ltd., Beijing, China

    Albert Cheung-Hoi Yu

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    Albert Cheung-Hoi Yu

  2. Neuroscience Research Institute, Peking University, Beijing, China

    Lina Li

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Gao, K. et al. (2018). Large De Novo Microdeletion in Epilepsy with Intellectual and Developmental Disabilities, with a Systems Biology Analysis. In: Cheung-Hoi Yu, A., Li, L. (eds) Systems Neuroscience. Advances in Neurobiology, vol 21. Springer, Cham. https://doi.org/10.1007/978-3-319-94593-4_9

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