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.