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Tim Footz, Ordan J Lehmann, Michael A Walter; Whole exome sequencing identifies new candidate genes for Pigment Dispersion Syndrome. Invest. Ophthalmol. Vis. Sci. 2016;57(12):795. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Pigment Dispersion Syndrome (PDS) is characterized by the loss of pigment granules from the iris and subsequent diffuse deposition in various ocular structures, notably the trabecular meshwork. PDS is typically found in young myopic males and often leads to increased intraocular pressure and progressive optic nerve degeneration (glaucoma). As the genetic etiology of PDS is currently unknown and since glaucoma is a prominent cause of blindness worldwide, we searched for the gene or genes responsible for the disease.
We used whole exome sequencing of DNA from two Mennonite families with PDS plus pigmentary glaucoma (PG) to search for gene variants that are associated with PDS+PG. Lists of candidate variants for each separate family were filtered using the following criteria: absence in the unaffected, absence in population-wide databases (e.g. dbSNP), high experimental significance (p-value <1E-20), functionally classified as non-synonymous (including frameshift and nonsense), and located in exons or near splicesites. Subjective criteria were also applied, such as manual determination of poor quality reads and alignments, and relevance of the gene’s expression to ocular disease.
Two PDS+PG samples from Family 1 were sequenced at 203x coverage. From Family 2 one unaffected, one PDS+PG, and two PDS samples were sequenced at 148x coverage. For Family 1 ten candidate variants, in ten different genes, were determined. In Family 2 five candidate variants, in five different genes, were determined, but none are in common with Family 1. Additional sequencing experiments are underway to validate the authenticity of the predicted variants and to determine if any of these 15 candidate genes contribute to disease-associated variation in 113 additional cases of PDS.
The identification of candidate genes for PDS is an important first step towards characterization of the pathways that result in pigmentary glaucoma. Improved screening for the genetic causes of glaucoma will lead to earlier diagnosis and treatment to better manage this form of irreversible blindness.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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