RT Journal Article
SR Electronic
T1 <em>CYP1B1</em> and <em>MYOC</em> variants in neonatal-onset versus infantile-onset primary congenital glaucoma
JF British Journal of Ophthalmology
JO Br J Ophthalmol
FD BMJ Publishing Group Ltd.
SP bjophthalmol-2020-318563
DO 10.1136/bjophthalmol-2020-318563
A1 Kaushik, Sushmita
A1 Luthra-Guptasarma, Manni
A1 Prasher, Dimple
A1 Dhingra, Deepika
A1 Singh, Nirbhai
A1 Kumar, Aman
A1 Sharma, Surya Prakash
A1 Kaur, Harpreet
A1 Snehi, Sagarika
A1 Thattaruthody, Faisal
A1 Pandav, Surinder Singh
YR 2021
UL http://bjo.bmj.com/content/early/2021/09/14/bjophthalmol-2020-318563.abstract
AB 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&gt;A, [p.R390H]. They required more surgeries and had a poorer outcome. On in-silico analysis c.1169G&gt;A, [p.R390H] scored very likely pathogenic. Two patients in the IO group who had the c.1294C&gt;G, [p.L432V] variant had a good outcome. Five of 14 NO-PCG and 8 of 29 IO-PCG harboured the variant c.227G&gt;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.