Abstract

Primary open angle glaucoma (POAG) is a major type of glaucoma characterized by progressive loss of retinal ganglion cells with associated visual field loss without an identifiable secondary cause. Genetic factors are considered to be major contributors to the pathogenesis of glaucoma. The aim of the study was to identify the causative gene in a large family with POAG by applying whole exome sequencing (WES). WES was performed on the DNA of four affected family members. Rare pathogenic variants shared among the affected individuals were filtered. Polymerase chain reaction and Sanger sequencing were used to analyze variants segregating with the disease in additional family members. WES analysis identified a variant in TP53BP2 (c.109G>A; p.Val37Met) that segregated heterozygously with the disease. In silico analysis of the substitution predicted it to be pathogenic. The variant was absent in public databases and in 180 population-matched controls. A novel genetic variant in the TP53BP2 gene was identified in a family with POAG. Interestingly, it has previously been demonstrated that the gene regulates apoptosis in retinal ganglion cells. This supports that the TP53BP2 variant may represent the cause of POAG in this family. Additional screening of the gene in patients with POAG from different populations is required to confirm its involvement in the disease.

Highlights

  • Glaucoma is a leading cause of irreversible blindness worldwide, affecting more than 60 million people around the world [1]

  • We used whole exome sequencing (WES) to identify the genetic defect in a large family with primary open angle glaucoma (POAG)

  • We identified potentially pathogenic variants in the TP53BP2 (c.109G>A; p.Val37Met) and MAPKAPK2 (c.305G>A; p.Arg102His) genes

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Summary

Introduction

Glaucoma is a leading cause of irreversible blindness worldwide, affecting more than 60 million people around the world [1]. Glaucoma comprises a group of heterogeneous optic neuropathies, characterized by progressive optic nerve degeneration. Primary open angle glaucoma (POAG) represents the major type of glaucoma affecting about 35 million people worldwide and is characterized by a juvenile or adult onset. Patients with POAG have characteristic glaucomatous optic nerve damage with corresponding visual field defects and an open anterior chamber angle at gonioscopy, but no other (congenital) anomalies [2, 3]. One of the significant risk factors for POAG is elevation of intraocular pressure (IOP). Well-studied risk factors associated with POAG include age, family history, gender, ethnicity, central corneal thickness, and myopia. Genetic factors play an important role in the disease etiology

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