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Biallelic variants in CPAMD8 are associated with primary open-angle glaucoma and primary angle-closure glaucoma
  1. Xueqing Li,
  2. Wenmin Sun,
  3. Xueshan Xiao,
  4. Lei Fang,
  5. Shiqiang Li,
  6. Xing Liu,
  7. Qingjiong Zhang
  1. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong, China
  1. Correspondence to Professor Qingjiong Zhang, Pediatric and Genetic Eye Clinic, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, 54 Xianlie Road, Guangzhou 510060, Guangdong, China; zhangqji{at}mail.sysu.edu.cn

Abstract

Background/Aims This study aims to assess the contribution of biallelic CPAMD8 variants in patients with different forms of glaucoma, especially primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), based on a systematic analysis of exome sequencing (ES).

Methods Potentially pathogenic CPAMD8 variants were selected from the ES data of 5307 subjects with various eye conditions through multiple bioinformatics analyses. Of the 5307 subjects, 1221 probands had different forms of primary glaucoma. The genotype–phenotype correlation was assessed by a systematic review of biallelic CPAMD8 variants that including our data and data from the literature. The expression profile of CPAMD8 in human tissues was determined at the mRNA and protein levels.

Results Biallelic CPAMD8 variants, including one frameshift and six missense variants, were exclusively present and significantly enriched in patients with glaucoma (one with juvenile open-angle glaucoma (JOAG), two with POAG and two with PACG) compared with none of the 4086 probands with other eye conditions in this cohort (p=4.1E-07). The effect of variants in these patients is relatively mild compared with that reported in patients with anterior segment dysgenesis or primary congenital glaucoma. CPAMD8 mRNA was highly expressed in the optic nerve, ciliary body, retina and iris, whereas the CPAMD8 protein was mainly detected in the nonpigmented epithelium of the iris and ciliary process, determined by immunohistochemistry.

Conclusions The data from this study not only provide further evidence to support the association of biallelic CPAMD8 variants with JOAG but also suggest that biallelic CPAMD8 variants might be associated with POAG and PACG.

  • ciliary body
  • genetics
  • glaucoma
  • iris
  • public health

Data availability statement

Data are available on reasonable request. The data in this article are available from the corresponding author on reasonable request.

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Data availability statement

Data are available on reasonable request. The data in this article are available from the corresponding author on reasonable request.

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Footnotes

  • Contributors XL carried out the experiments and prepared tables and figures. QZ and XL analysed the data. XL, XX, SL and LF recruited subjects. QZ, XL, and WS participated in drafting of the manuscript. QZ designed and supervised this work, collected exome sequencing data for CPAMD8, as well as revised the manuscript.

  • Funding This work was supported by the Fundamental Research Funds of the State Key Laboratory of Ophthalmology.

  • Competing interests None declared.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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