Identification of TP53BP2 as a Novel Candidate Gene for Primary Open Angle Glaucoma by Whole Exome Sequencing in a Large Multiplex Family.
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.
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.|Department of Clinical Genetics, Academic Medical Centre, Amsterdam, the Netherlands.
Shazia
S
Micheal
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Nicole T M
NTM
Saksens
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Barend F
BF
Hogewind
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Muhammad Imran
MI
Khan
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
Carel B
CB
Hoyng
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands. Anneke.denHollander@radboudumc.nl.|Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands. Anneke.denHollander@radboudumc.nl.
Anneke I
AI
den Hollander
D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D003198:Computer Simulation; D059472:Exome; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005902:Glaucoma, Open-Angle / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D000073359:Exome Sequencing
D051017:Apoptosis Regulatory Proteins; C090468:TP53BP2 protein, human
Primary open angle glaucoma; TP53BP2; Whole exome sequencing