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

Authors: Yunsheng, Qiao; Tingting, Shao; Yuhong, Chen; Junyi, Chen; Xinghuai, Sun; Xueli, Chen;

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

Abstract

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.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.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.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.

Related Organizations
Keywords

Mutation, East Asian People, Humans, High-Throughput Nucleotide Sequencing, Proteins, Glaucoma, Placenta Growth Factor

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
3
Top 10%
Average
Average
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