LTBP2 gene analysis in the GLC3C-linked family and 94 CYP1B1-negative cases with primary congenital glaucoma

Abstract

Purpose: Primary congenital glaucoma (isolated trabeculodysgensis, PCG) generally presents between birth and 3 years of age. Recently, mutations in Latent Transforming Growth Factor (TGF)-beta Binding Protein 2 (LTBP2) have been reported in several families that were diagnosed with PCG, who actually had a more complex ocular phenotype with ectopia lentis and Marfanoid features. We screened this gene for mutations in the original Turkish GLC3C-linked PCG family and in a group of CYP1B1-negative British PCG cases and their matched normal control subjects.

Methods: The 36-coding exons of the LTBP2 gene were sequenced in 94 familial or sporadic CYP1B1-negative PCG cases and 96 matched normal control subjects.

Results: No disease-causing mutations were identified in the original GLC3C-linked family. Screening of LTBP2 in 94 PCG and 96 control subjects identified three novel synonymous variations (L429L, P680P, S1031S) in 12 PCG and seven control subjects. A novel heterozygous missense mutation (R538W) was also identified in 1 of 90 PCG cases that is unlikely to be disease-causative.

Conclusions: LTBP2 mutations were not found in the Turkish GLC3C-linked PCG family or in 94 British CYP1B1-negative PCG cases. Our data suggest that LTBP2 mutations are not a significant cause for isolated trabeculodysgenesis.

KEYWORDS::

• LTBP2
• PCG
• GLC3C
• CYP1B1-Negative

ACKNOWLEDGMENTS

We particularly want to thank the patients and families who have generously volunteered their time and provided samples for this study. We are also indebted to Mr Glen Brice and clinical colleagues for family ascertainment, clinical information and initial blood sampling of the individual subjects in this study.

Declaration of interest: This work was supported in part by The International Glaucoma Association (UK), The Glaucoma Foundation (New York), The US National Institutes of Health (National Eye Institute), Rosetrees Trust (UK), The Bluff Field Charitable Trust, St. George’s NHS Hospital Trust, St. George’s, University of London (UK), the NIHR Biomedical Research Center at Moorfields Eye Hospital and UCL Institute of Ophthalmology. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.