<i>CYP1B1</i> and <i>MYOC</i> variants in neonatal-onset versus infantile-onset primary congenital glaucoma.

Abstract

To compare <i>CYP1B1</i> and <i>MYOC</i> variants in a cohort of neonatal-onset (NO) and infantile-onset (IO) primary congenital glaucoma (PCG). 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. <i>CYP1B1</i> and <i>MYOC</i> 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. Babies with <i>CYP1B1</i> 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 <i>CYP1B1</i> 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 <i>MYOC</i> gene, which was scored benign by in-silico analysis, and was also found in 2 of 15 normal controls. Patients with <i>CYP1B1</i> pathogenic variants had a poorer outcome than those without. We found more NO PCG babies with <i>CYP1B1</i> mutations compared with IO PCG. This may be one of the reasons for NO PCG having a poorer prognosis compared with IO PCG.