Case Report
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Jan 26, 2021; 9(3): 697-706
Published online Jan 26, 2021. doi: 10.12998/wjcc.v9.i3.697
Coinheritance of OLFM2 and SIX6 variants in a Chinese family with juvenile-onset primary open-angle glaucoma: A case report
Xue Yang, Nan-Nan Sun, Zhen-Ni Zhao, Shu-Xiang He, Miao Zhang, Dan-Dan Zhang, Xiao-Wei Yu, Jia-Min Zhang, Zhi-Gang Fan
Xue Yang, Nan-Nan Sun, Zhen-Ni Zhao, Miao Zhang, Dan-Dan Zhang, Xiao-Wei Yu, Jia-Min Zhang, Zhi-Gang Fan, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, Guangdong Province, China
Shu-Xiang He, Guangzhou KingMed Diagnostics Group Co., Ltd, Guangzhou 510060, Guangdong Province, China
Author contributions: Fan ZG conceived and designed the study; Zhang M, Yu XW and Zhang JM performed the experiments; Yang X, Zhao ZN and Zhang DD provided clinical research; Yang X and Sun NN wrote the manuscript; Yang X, Sun NN, He SX and Fan ZG reviewed and edited the manuscript; all authors read and approved the manuscript.
Supported by the Guangzhou Science and Technology Plan Project, No. 201803040020 and 201903010065; the Guangdong Natural Science Foundation, No. 2020A1515010168; and the Research Funds of the State Key Laboratory of Ophthalmology, No. PT1001022.
Informed consent statement: Informed written consent was obtained from the patient for publication of this report and any accompanying images.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhi-Gang Fan, MD, PhD, Professor, Chief Doctor, State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, No. 7 Jinsui Road, Tianhe District, Guangzhou 510060, Guangdong Province, China. fanzhg3@mail.sysu.edu.cn
Received: September 14, 2020
Peer-review started: September 14, 2020
First decision: November 20, 2020
Revised: November 26, 2020
Accepted: December 6, 2020
Article in press: December 6, 2020
Published online: January 26, 2021
Abstract
BACKGROUND

Juvenile-onset primary open-angle glaucoma (JOAG), characterized by severe elevation of intraocular pressure and optic neuropathy prior to the age of 40, is a rare subtype of primary open-angle glaucoma. Several genetic mutations have been associated with JOAG.

CASE SUMMARY

The proband patient was a young male, diagnosed with primary open-angle glaucoma at the age of 27. The patient and his unaffected parents who have been excluded from classic genetic mutations for primary open-angle glaucoma were included to explore for other possible genetic variants through whole genome sequencing and bioinformatics analysis. In this trio, we found two heterozygous variants inherited from the parents in the proband: c.281G>A, p.Arg94His in OLFM2 and c.177C>G, p.Ile59Met in SIX6. Both genetic mutations are predicted through bioinformatics analysis to replace evolutionary conserved amino acids, therefore rendering a pathogenic effect on proteins. In contrast, very low frequencies for these genetic mutations were recorded in most common control databases.

CONCLUSION

This is the first report on coinherited mutations of OLFM2 and SIX6 in a JOAG family, which shows the complexity of JOAG inheritance. Large-scale clinical screening and molecular functional investigations on these coinherited mutations are imperative to improve our understanding of the development of JOAG.

Keywords: Juvenile-onset primary open-angle glaucoma, Whole genome sequencing, Co-inheritance, OLFM2, SIX6, Case report

Core Tip: This report describes a case of juvenile-onset primary open-angle glaucoma (JOAG) with a coinheritance of OLFM2 and SIX6 variants, which might contribute to the onset of JOAG. This finding may enrich the genetic spectrum of JOAG and prompt us to further investigate the functional effects of the two variants on JOAG.