gene mutations cause high myopia in humans and mice.

Apr 11, 2022

Contributor: Qi Tian,Ping Tong,Gong Chen,Meichun Deng,Tian'e Cai,Runyi Tian,Zimin Zhang,Kun Xia,Zhengmao Hu

gene mutations cause high myopia in humans and mice.

High myopia (HM) is a leading cause of blindness that has a strong genetic predisposition. However, its genetic and pathogenic mechanisms remain largely unknown. Thus, this study aims to determine the genetic profile of individuals from two large Chinese families with HM and 200 patients with familial/sporadic HM. We also explored the pathogenic mechanism of HM using HEK293 cells and a mouse model.
The participants underwent genome-wide linkage analysis and exome sequencing. Visual acuity, electroretinogram response, refractive error, optical parameters and retinal rod cell genesis were measured in knockout mice. Immunofluorescent staining, biotin-labelled membrane protein isolation and electrophysiological characterisation were conducted in cells transfected with overexpression plasmids.
A novel HM locus on Xp22.2-p11.4 was identified. Variant c.539C>T (p.Pro180Leu) in gene was co-segregated with HM in the two families. Another variant, c.458G>A (p.Arg153Gln), was identified in a sporadic sample. The knockout mice showed myopia-related phenotypes, decreased electroretinogram responses and impaired retinal rod cell genesis. Variants c.458G>A and c.539C>T altered the localisation of GlyRα2 on the cell membrane and decreased agonist sensitivity.
was identified as a novel HM-causing gene. Its variants would cause HM through altered visual experience by impairing photoperception and visual transmission.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

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About The Expert

Qi Tian

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Ping Tong

Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China huzhengmao@sklmg.edu.cn tongping@csu.edu.cn xiakun@sklmg.edu.cn.

Gong Chen

Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Meichun Deng

Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Province Key Laboratory of Basic and Applied Hematology, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Department of Biochemistry and Molecular Biology, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Tian’e Cai

Reproductive Center, Sanya Central Hospital, Sanya, Hainan, People’s Republic of China.

Runyi Tian

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Zimin Zhang

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Kun Xia

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China huzhengmao@sklmg.edu.cn tongping@csu.edu.cn xiakun@sklmg.edu.cn.

Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Zhengmao Hu

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China huzhengmao@sklmg.edu.cn tongping@csu.edu.cn xiakun@sklmg.edu.cn.

Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

Hunan Key Laboratory of Animal Models for Human Disease, School of Life Sciences, Central South University, Changsha, Hunan, People’s Republic of China.

References

PubMed