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A Novel Nonsense Mutation in ARR4 Leads to X-linked High Myopia: A Genetic Paradox
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  • Dejian Yuan,
  • Tizhen Yan,
  • Ning Tang,
  • Shiqiang Luo,
  • Biao Yin,
  • Jun Huang,
  • Jianqiang Tan,
  • Qiuhua Wang,
  • Xin Zhong,
  • Ling Zhang,
  • Meirong Wei,
  • Victor Wei Zhang,
  • Lizhu Chen,
  • Xiaoli Liu,
  • Li Xie,
  • Zehui Xu,
  • Yueyuan Lan,
  • Taobo Hu,
  • Jing Guo,
  • Zhong Lin
Dejian Yuan
Liuzhou Maternal and Child Healthcare Hospital
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Tizhen Yan
Liuzhou Maternal and Child Healthcare Hospital
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Ning Tang
Liuzhou Maternal and Child Healthcare Hospital
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Shiqiang Luo
Liuzhou Maternal and Child Healthcare Hospital
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Biao Yin
Liuzhou Maternal and Child Healthcare Hospital
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Jun Huang
Liuzhou Maternal and Child Healthcare Hospital
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Jianqiang Tan
Liuzhou Maternal and Child Healthcare Hospital
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Qiuhua Wang
Liuzhou Maternal and Child Healthcare Hospital
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Xin Zhong
Liuzhou Maternal and Child Healthcare Hospital
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Ling Zhang
Liuzhou Maternal and Child Healthcare Hospital
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Meirong Wei
Liuzhou Maternal and Child Healthcare Hospital
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Victor Wei Zhang
Baylor College of Medicine Department of Molecular and Human Genetics
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Lizhu Chen
Liuzhou Maternal and Child Healthcare Hospital
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Xiaoli Liu
Liuzhou Maternal and Child Healthcare Hospital
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Li Xie
Liuzhou Maternal and Child Healthcare Hospital
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Zehui Xu
Liuzhou Maternal and Child Healthcare Hospital
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Yueyuan Lan
Liuzhou Maternal and Child Healthcare Hospital
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Taobo Hu
Peking University People’s Hospital
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Jing Guo
Sun Yat-sen University First Affiliated Hospital
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Zhong Lin
Liuzhou Maternal and Child Healthcare Hospital
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Abstract

ARR4 has been associated with X-linked, female-limited, high myopia. However, using exome sequencing (ES) in a Southern Chinese family, we identified the first hemizygous high myopia case in a male patient. A novel truncated mutation (ARR4: c.569C>G, p.S190*), which co-segregated with the disease phenotype in affected members, was identified in this family. Because the proband’s father was a hemizygote for the ARR4 variant, the present study demonstrated a case where high myopia caused by ARR4 is not X-linked, female-limited. This implied that a complicated X-linked inheritance pattern may exist for ARR4. Thus, the results of this study expanded the variant spectrum in ARR4 and provided additional information for genetic counseling, prenatal testing and diagnosis. Moreover, we characterized the pathogenic role of ARR4 c.569C>G (p.S190*) and demonstrated that the mutant protein accumulated under ER stress and was degraded by the proteasome.