Screening of candidate genes at GLC3B and GLC3C loci in Chinese primary congenital glaucoma patients with targeted next generation sequencing

ABSTRACT

Background

Primary congenital glaucoma (PCG) is characterized by developmental abnormalities of the anterior chamber angle. Although several genes have been associated with PCG, pathogenic mutations could only be detected in about 20% of Chinese patients. GLC3B (1p36.2–36.1) and GLC3C (14q24.3) loci were previously identified in PCG pedigrees via linkage analysis. However, no causative genes were reported in these loci. This study was designed to search for novel PCG-related genes in these genetic regions.

Materials and methods

DNA samples from 100 PCG patients and 200 normal controls were pooled and sequenced using a customized panel of 133 positional candidate genes located around GLC3B and GLC3C loci (±1Mb). PCG-related genes were prioritized by the distribution of variants between patients and controls. Confirmation of selected variants and co-segregation analysis were performed using Sanger sequencing.

Results

Patient and control group contained 116 and 147 rare variants respectively after screening. Three genes (ZC2HC1C, VPS13D, and PGF) were prioritized according to the distribution of variants between the two groups. Rare variants of PGF were only identified in PCG patients.

Conclusions

To the best of our knowledge, this is the first study aiming at exploring novel PCG-related genes at GLC3B and GLC3C loci. Our preliminary results suggest that there are potential associations between ZC2HC1C, VPS13D, PGF, and PCG. However, larger cohort studies and functional assays are required to provide further evidence for the proposed genotype-phenotype association.

KEYWORDS:

• Primary congenital glaucoma
• next generation sequencing
• novel PCG-related genes

Acknowledgement

The samples used for the analyses described in this manuscript were obtained from the EENT Biobank. We would like to thank all the participants and the staffs for their valuable contribution to this research.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Author’s contributions

X.C., J.C., and X.S. conceived and designed the study; Y.C., J.C., and X.C. recruited participants and collected the samples; Y.Q. and T.S. made contributions to data acquisition and analysis; Y.Q. drafted the manuscript. All authors reviewed and approved the final manuscript.

Availability of data and materials

The datasets generated and analysed during the current study are available in NCBI under the accession number PRJNA802337 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA802337/).

Ethics approval and consent to participate

This study was approved by the Human Research Ethics Committee of the Eye and ENT Hospital of Fudan University and adhered to the tenets of the Declaration of Helsinki. All subjects or their legal guardians have provided written informed consents.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/13816810.2022.2109683.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81770968 to X.C., 81870661 to J.C.].