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Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis

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Abstract

Our study is aimed to explore the underlying genetic basis of myasthenia gravis. We collected a Chinese pedigree with myasthenia gravis, and whole-exome sequencing was performed on the two affected siblings and their parents. The candidate pathogenic gene was identified by bioinformatics filtering, which was further verified by Sanger sequencing. The homozygous mutation c.G40A (p.V14M) in interferon gamma receptor 1was identified. Moreover, the mutation was also detected in 3 cases of 44 sporadic myasthenia gravis patients. The p.V14M substitution in interferon gamma receptor 1 may affect the signal peptide function and the translocation on cell membrane, which could disrupt the binding of the ligand of interferon gamma and antibody production, contributing to myasthenia gravis susceptibility. We discovered that a rare variant c.G40A in interferon gamma receptor 1 potentially contributes to the myasthenia gravis pathogenesis. Further functional studies are needed to confirm the effect of the interferon gamma receptor 1 on the myasthenia gravis phenotype.

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Funding

This work was supported by the Shijiazhuang Science and Technology Bureau Foundation (No. 131460613), Science and Technology Agency Foundation of Hebei Province (No. 14277758D), Natural Science Foundation of Hebei Province (No. H2015106020), and Key Project of Hebei Provincial Administration of Traditional Chinese Medicine (No. 2014221).

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  1. Guoyan Qi and Peng Liu contributed equally to this work.

Authors and Affiliations

  1. Center of Treatment of Myasthenia Gravis Hebei Province, First Hospital of Shijiazhuang, Fangbei road No. 9, Shijiazhuang, Hebei Province, 050011, China

    Guoyan Qi, Peng Liu, Shanshan Gu, Hongxia Yang, Huimin Dong & Yinping Xue

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  1. Guoyan Qi
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  2. Peng Liu
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Correspondence to Guoyan Qi.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Qi, G., Liu, P., Gu, S. et al. Whole-exome sequencing reveals a rare interferon gamma receptor 1 mutation associated with myasthenia gravis. Neurol Sci 39, 717–724 (2018). https://doi.org/10.1007/s10072-018-3275-8

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