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.
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.
摘要：
UNASSIGNED：原发性先天性青光眼（PCG）的特征是前房角发育异常。尽管有几个基因与PCG相关，仅在约20%的中国患者中检测到致病突变.先前通过连锁分析在PCG家系中鉴定了GLC3B(1p36.2-36.1)和GLC3C(14q24.3)基因座。然而,在这些基因座中没有致病基因的报道。本研究旨在在这些遗传区域中寻找新的PCG相关基因。
UNASSIGNED：将来自100名PCG患者和200名正常对照的DNA样本合并并使用位于GLC3B和GLC3C基因座（±1Mb）周围的133个位置候选基因的定制组进行测序。PCG相关基因通过变异在患者和对照之间的分布而被优先考虑。使用Sanger测序进行所选变体的确认和共分离分析。
UNASSIGNED：患者组和对照组在筛选后分别含有116和147个罕见变异。三个基因（ZC2HC1C，VPS13D,和PGF）根据两组之间的变体分布进行优先排序。仅在PCG患者中发现了罕见的PGF变体。
未经授权：据我们所知，这是第一项旨在探索GLC3B和GLC3C位点的新PCG相关基因的研究。我们的初步结果表明，ZC2H1C之间存在潜在的关联，VPS13D,PGF,和PCG。然而,需要进行更大规模的队列研究和功能检测,以便为所提出的基因型-表型关联提供进一步的证据.
UNASSIGNED：将来自100名PCG患者和200名正常对照的DNA样本合并并使用位于GLC3B和GLC3C基因座（±1Mb）周围的133个位置候选基因的定制组进行测序。PCG相关基因通过变异在患者和对照之间的分布而被优先考虑。使用Sanger测序进行所选变体的确认和共分离分析。
UNASSIGNED：患者组和对照组在筛选后分别含有116和147个罕见变异。三个基因（ZC2HC1C，VPS13D,和PGF）根据两组之间的变体分布进行优先排序。仅在PCG患者中发现了罕见的PGF变体。
未经授权：据我们所知，这是第一项旨在探索GLC3B和GLC3C位点的新PCG相关基因的研究。我们的初步结果表明，ZC2H1C之间存在潜在的关联，VPS13D,PGF,和PCG。然而,需要进行更大规模的队列研究和功能检测,以便为所提出的基因型-表型关联提供进一步的证据.
