Analysis of early-onset glaucoma genes in primary congenital glaucoma patients residing in North India identifies an additional case with THBS1 Arg1034Cys

Purpose To analyze exome sequence data from Indian cases with primary congenital glaucoma (PCG) for pathogenic variants.Materials/Methods In this cross-sectional observational study, ten consecutive, unrelated patients with a clinical diagnosis of PCG residing in India were enrolled. Medical history, family history, and complete ocular examination were carried out for all patients. Whole-exome sequencing was performed and analyzed for pathogenic variants.Results Pathogenic or likely pathogenic variants in CYP1B1 and FOXC1 were identified in 3 cases, CYP1B1 c.1169 G>A; p.Arg390His (homozygous in 2 cases) and FOXC1 c479_481; p.Asn160del in one case. One case carried a single CYP1B1 allele c.1094 G>A; p.Gly365Glu that was predicted to be pathogenic and another case carried a TEK variant of uncertain significance (c.1798 G>T; p.Val600Leu). Of interest, one case was found to harbor a recently described THBS1 missense allele (c.3100C>T; p.Arg1034Cys) involving the same amino acid residue (p.Arg1034) previously found to be altered in three PCG families with diverse ancestry.Conclusions Likely disease-causing variants in previously known early onset glaucoma genes were identified in 4 of 10 cases analyzed in this study, including a recurrent THBS1 missense mutation p.Arg1034Cys. This study is the second report of a THBS1 missense mutation in PCG and provides additional support for the contribution of this gene to PCG phenotypes.