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Vision science
Original article
TNFRSF21 mutations cause high myopia
  1. Hong Pan1,2,3,
  2. Shijing Wu1,
  3. Jing Wang4,
  4. Tian Zhu1,
  5. Tengyan Li3,
  6. Bo Wan1,
  7. Beihong Liu2,3,
  8. Yan Luo1,
  9. Xu Ma2,3,
  10. Ruifang Sui1,
  11. Binbin Wang2,3
  1. 1 Department of Ophthalmology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
  2. 2 Graduate School of Peking Union Medical College, Beijing, China
  3. 3 Center for Genetics, National Research Institute for Family Planning, Beijing, China
  4. 4 Department of Medical Genetics and Developmental Biology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
  1. Correspondence to Professor Ruifang Sui, Department of Ophthalmology, Peking Union Medical College Hospital, Beijing 100730, China; hrfsui{at}163.com; Professor Binbin Wang, Center for genetics, National Research Institute for Family Planning, Beijing 100081, China; wbbahu{at}163.com; Professor Xu Ma, Center for genetics, National Research Institute for Family Planning, Beijing 100081, China; genetic88{at}126.com

Abstract

Background High myopia (HM) is one of the leading causes of vision impairment worldwide, accompanied by a series of pathological ocular complications. Studies have shown that genetic factors play an important role in the pathogenesis of HM. The aim of our study is to identify a candidate gene for a large family with non-syndromic HM.

Methods A large Chinese family, including 12 patients with non-syndromic HM, and 220 unrelated patients with HM, were recruited from the Department of Ophthalmology, Peking Union Medical College Hospital. Three affected subjects from the large family were selected to perform whole exome sequencing (WES). Rare heterozygous variants shared by all three subjects were retained and then Sanger sequencing was used to determine whether any of the remaining variants cosegregated with the disease phenotype. Furthermore, all coding regions of the candidate genes were analysed in 220 unrelated patients with HM. Immunofluorescence assay was used to detect the expression of the candidate gene in the eye. Annexin V/PI staining and flow cytometry were applied to detect cell apoptotic changes.

Results WES identified a novel TNF receptor superfamily member 21 (TNFRSF21) variant, P146A, in a large Chinese family with HM, and another three rare heterozygous variants (P202L, E240* and A440G) in TNFRSF21 were found in 220 unrelated cases with HM. Immunofluorescence assay indicated that it is strongly expressed in the mouse eye. Compared with the wild type, the P146A variant could significantly increase adult retinal pigment epithelial cell line-19 cell apoptotic levels.

Conclusions Variants in TNFRSF21 cause non-syndromic HM in Chinese population.

  • high myopia
  • whole exome sequencing
  • TNFRSF21

https://doi.org/10.1136/jmedgenet-2018-105684

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    Footnotes

    • HP and SW contributed equally.

    • XM, RS and BW contributed equally.

    • Contributors HP and SW wrote the manuscript. HP and JW performed the WES data analysis. RS, SW, TZ, BW and YL examined the patients and collected all the HM samples. HP and BL carried out the functional experiments. The Sanger sequencing in unrelated patients with HM was performed by HP and TL. XM, RS and BW designed the experiments.

    • Funding This work was supported by the National Key Research and Development Program of China (2016YFC1000307), the Central Public Interest Scientific Institution Basal Research Fund (2019GJZ02), the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS 2016-12M-1-002), the National Natural Science Foundation of China (81873687), the National Science and Technology Basic Work (2014FY130100) and the National Infrastructure of Chinese Genetic Resources (YCZYPT [2017]01-6).

    • Competing interests None declared.

    • Patient consent for publication Obtained.

    • Ethics approval The study was approved by the Institute Review Board of PUMCH and the National Research Institute for Family Planning.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information.