Research Paper Volume 13, Issue 19 pp 23338—23347
A novel mutation in PCK2 gene causes primary angle-closure glaucoma
- 1 Department of Ophthalmology, 3201 Hospital, Xi’an Jiaotong University Health Science Center, Hanzhong, Shaanxi 723000, China
- 2 The First People’s Hospital of Xianyang, Xianyang, Shaanxi 712000, China
- 3 Department of Ophthalmology, Shaanxi Provincial People’s Hospital, Xi’an, Shaanxi 710068, China
- 4 College of Medical Laboratory Science, Guilin Medical University, Guilin, Guangxi 541004, China
- 5 Guihang Guiyang Hospital Affiliated to Zunyi Medical University, Guiyang, Guizhou 550000, China
Received: August 4, 2021 Accepted: October 3, 2021 Published: October 14, 2021
https://doi.org/10.18632/aging.203627How to Cite
Copyright: © 2021 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Primary angle-closure glaucoma (PACG) is an ophthalmic genetic disease characterized by direct contact between the iris and trabecular meshwork, resulting in an obstructed outflow of aqueous humor from the eye. However, it is unclear as to what role genetics plays in the development of PACG. The present study investigated the disease-causing mutation in a five-generation Chinese PACG family using whole-genome sequencing. A novel heterozygous missense mutation c.977C>T in PCK2 gene was identified in five affected family members, but not in any unaffected and 86 unrelated healthy individuals. This nucleotide substitute is predicted to result in a proline to leucine substitution p.Pro326Leu. Furthermore, the function of this mutation was analyzed through various in vitro assays using the RGC-5 cell line. Our results demonstrate that the p.Pro326Leu mutation induces RGC-5 cell cycle arrest and apoptosis with a decreased BcL-XL. The increasing P53, P27, P21, AKT, and P-GSK3α were also detected in the cells transfected with c.977C>T mutation, suggesting that this mutation within PCK2 gene cause PACG through impairment of AKT/GSK3α signaling pathway.