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Diem K Bui, Nieraj Jain, G Baker Hubbard, Suma Shankar; Novel genetic variants causing hereditary vitreoretinopathies. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3147.
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© ARVO (1962-2015); The Authors (2016-present)
Hereditary vitreoretinal degenerations encompass a heterogeneous group of disorders characterized by variable ocular and orofacial features and skeletal abnormalities. We report novel disease-causing genetic variants and characterize the associated phenotypes, expanding the clinical and genotypic spectrum of these vitreoretinopathies.
We retrospectively identified individuals with a clinical diagnosis of hereditary vitreoretinopathy presenting to our institution from 2010 to 2015 and harboring novel disease-causing genetic variants, as determined by targeted next generation sequencing and array complimentary genomic hybridization. We characterized the associated clinical features and severity of disease in these individuals.
Five subjects were identified, all of whom developed visual symptoms between the ages of 3 and 10. Three subjects had a clinical diagnosis of Stickler syndrome, with features of high myopia, retinal detachment, cataract, and characteristic systemic findings. Best corrected visual acuity ranged from 20/25 to loss of the eye and no light perception. These subjects had novel mutations in the COL2A1 gene on 12q: c.1052delG (frameshift), c.2530C>T (p.Q844X), and intragenic deletion of exon 45 to exon 52. One subject with eye involvement as well as developmental delay and failure to thrive had a 12q12-q13.11 deletion including the entire COL2A1 gene. Another subject with bilateral retinal detachment and severe pigmentary retinopathy had a de novo heterozygous, likely pathogenic deletion encompassing exon 8 of the VCAN gene on 5q. The subject with the contiguous deletion including the entire COL2A1 gene had the most severe phenotype and the subject with the intragenic deletion in COL2A1 had the mildest phenotype. All cases demonstrated autosomal dominant inheritance.
Genetic testing is an invaluable adjunctive tool for diagnosis and counseling in conditions with phenotypic variability. This study expands the clinical and genotypic spectrum of hereditary vitreoretinopathies. These novel mutations are all autosomal dominant and this information as well as targeted testing of family members can help in more accurate risk predictions and disease management.
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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