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A novel heterozygous c.733 T > G MYOC mutation associated with juvenile-onset open-angle glaucoma in a Chinese family

Eye volume 37, pages 2488–2493 (2023)Cite this article

Subjects

Abstract

Aims

To detect mutations in juvenile-onset open-angle glaucoma in a Chinese family and to describe the characteristic ophthalmic phenotypes of this pedigree.

Methods

There were 14 individuals in this four-generation pedigree. All living members of the family underwent comprehensive ophthalmic examinations. Five patients presented with elevated intraocular pressures. All of them shared early-onset disease, with a mean onset age of 14.4 years and continuing aggressive damage to their optic nerves. Hyperpigmentation in the trabecular meshwork and sometimes-broad iris processes were noted in this family using gonioscopy. All exons of candidate genes (MYOC, OPTN, CYP1B1) were amplified using the polymerase chain reaction, and analysed with an ABI 3700XL Genetic Analyser.

Results

A heterozygous missense mutation in exon 3 (c.733 T > G) of the MYOC gene was found in the five JOAG patients and one 7-year-old boy with no ophthalmic manifestation of glaucoma, but it was absent in other members of the family and in the controls. This mutation resulted in a transversion of cysteine to glycine (Cys245Gly).

Conclusions

We concluded the novel MYOC c.733 T > G mutation found in a Chinese family with JOAG caused a severe type of JOAG exhibiting early onset, high IOP, and severe optic nerve damage. Interestingly, unlike other reported MYOC mutation families, our patients exhibited marked angle pigmentation and iris processes.

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Fig. 1: The hereditary features of the family.
Fig. 2: Optic disc features of affected members with varying ages and disease durations.
Fig. 3: Goniophotographs showed that the features of the anterior chamber angle in the family varied with age. TM: the trabecular meshwork.
Fig. 4: Model of the OLF domain of the Cys245Gly myoc protein, combined from the two structures. The two cysteines are highlighted as spheres (245 in red, 433 in yellow).

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Data availability

The data that support the findings of this study are available on reasonable request from the corresponding author.

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Acknowledgements

We thank Wei Liu and Lili Chen for their work in collecting clinical data. We also thank Dr. Zhe Sun for assistance with structural modelling.

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Author notes

  1. These authors contributed equally: Aiai Dai, Xuan Cheng.

Authors and Affiliations

  1. Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Aiai Dai

  2. Senior Department of Ophthalmology, the Third Medical Center of PLA General Hospital, Beijing, China

    Xuan Cheng, Runpu Li, Xuhui Gao, Shuxian Li & Tiecheng Liu

  3. Department of Gastroenterology and Hepatology, Guangdong Second Provincial General Hospital, Guangdong, China

    Weifeng Wang

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Contributions

Study concept and design: TL, AD and XC. Data collection, analysis and interpretation: AD, XC, WW, RL, XG and SL. Drafting the article: AD and XC. Critical revision of the manuscript: TL and WW. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Tiecheng Liu.

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Dai, A., Cheng, X., Wang, W. et al. A novel heterozygous c.733 T > G MYOC mutation associated with juvenile-onset open-angle glaucoma in a Chinese family. Eye 37, 2488–2493 (2023). https://doi.org/10.1038/s41433-022-02359-x

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