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David Andrew Terrell, Rachel M Huckfeldt, Eric A Pierce, Emily Margaret Place; Phenotypic variability in patients with CDHR1 mutations. Invest. Ophthalmol. Vis. Sci. 2019;60(9):376.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this project was to evaluate any genotype-specific influences of the phenotypic variability associated with CDHR1.
We identified patients evaluated at Massachusetts Eye and Ear for whom next generation sequencing with the Genetic Eye Disease panel for retinal genes identified pathogenic variants in CDHR1. Clinical data including visual acuity, Goldmann visual fields, electrophysiology, and retinal imaging was assessed.
Seven patients (ages 28-69) were identified with two pathogenic CDHR1 variants, and all possessed at least one copy of the synonymous c.783G>A mutation (p.Pro216Pro). Three individuals were homozygous for this mutation whereas the other four were heterozygous. Segregation testing was performed in heterozygous cases. Three of the patients had macula-predominant disease with full field ERGs that were only mildly subnormal. One of these individuals was homozygous for the c.783G>A mutation whereas the other were compound heterozygous. The additional four subjects had retinitis pigmentosa, and of these, two were homozygous for synonymous c.783G>A mutation.
Evaluation revealed significant phenotypic variability even among patients with the same genotype. These data emphasize the contributions of genetic modifiers and other factors to phenotype. Furthermore, the synonymous c.783G>A mutation has previously been suggested to cause only mild abnormality of protein function, and data from our case series suggests that this pathogenic variant gives rise to a wide array of clinical disease.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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