Objective To compare CYP1B1 and MYOC variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG). Methods This prospective observational study included 43 infants with PCG (14 NO and 29 IO) presenting between January 2017 and January 2019 with a minimum 1-year follow-up. CYP1B1 and MYOC genes were screened using Sanger sequencing with in-silico analysis of the variants using Polymorphism Phenotyping v.2 and Protein Variation Effect Analyser platforms. Allelic frequency was estimated using Genome Aggregation Database (gnomAd). Disease presentation and outcome were correlated to the genetic variants in both groups. Results Babies with CYP1B1 mutations had more severe disease at presentation and worse outcomes. Six of 14 (42.8%) NO glaucoma and 5 of 29 (17.2%) IO harboured CYP1B1 mutations. Five of six babies in the NO group and three of five in the IO group harboured the variant c.1169G>A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G>A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C>G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G>A, [p.R76K] in the MYOC gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls. Conclusions Patients with CYP1B1 pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with CYP1B1 mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG. Data are available upon reasonable request. All data relevant to the study are available on reasonable request.

中文翻译：

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新生儿发病与婴儿发病原发性先天性青光眼中的 CYP1B1 和 MYOC 变异

目的 比较新生儿发病 (NO) 和婴儿发病 (IO) 原发性先天性青光眼 (PCG) 队列中的 CYP1B1 和 MYOC 变异。方法 这项前瞻性观察研究纳入了 2017 年 1 月至 2019 年 1 月期间就诊的 43 名 PCG 婴儿（14 名 NO 和 29 名 IO），并进行了至少 1 年的随访。使用 Sanger 测序筛选 CYP1B1 和 MYOC 基因，并使用 Polymorphism Phenotyping v.2 和 Protein Variation Effect Analyzer 平台对变异进行计算机分析。使用基因组聚合数据库 (gnomAd) 估计等位基因频率。疾病表现和结果与两组的遗传变异相关。结果 CYP1B1 突变的婴儿在就诊时有更严重的疾病和更差的结果。14 例 NO 青光眼中有 6 例 (42.8%) 和 29 例 IO 青光眼中有 5 例 (17.2%) 携带 CYP1B1 突变。NO 组的 6 个婴儿中有 5 个和 IO 组的 5 个婴儿中有 3 个携带变异体 c.1169G>A，[p.R390H]。他们需要更多的手术并且结果更差。在计算机分析中，c.1169G>A，[p.R390H] 得分很可能致病。IO 组中有 c.1294C>G，[p.L432V] 变体的两名患者有良好的结果。14 例 NO-PCG 中的 5 例和 29 例 IO-PCG 中的 8 例在 MYOC 基因中携带变异 c.227G>A，[p.R76K]，通过计算机分析评分为良性，并且还在 15 例中的 2 例中发现正常控制。结论 具有 CYP1B1 致病性变异的患者比没有的患者预后更差。与 IO PCG 相比，我们发现更多具有 CYP1B1 突变的 NO PCG 婴儿。这可能是 NO PCG 与 IO PCG 相比预后较差的原因之一。可根据合理要求提供数据。