Clinical and Molecular Findings in a CDHR1 Retinal Dystrophy Cohort

Abstract

Purpose : The cadherin-related family member 1 is a transmembrane photoreceptor protein encoded by CDHR1 (OMIM 609502). Mutations in CDHR1 are associated with cone-rod dystrophy (CRD 15), retinitis pigmentosa (RP 65) and late-onset macular dystrophy. This work aims to:
1. Describe the clinical and molecular findings in a retinal dystrophy cohort attributed to autosomal recessive CDHR1 variants.
2. Report novel pathogenic CDHR1 variants in ethnic/racial groups not previously known to be affected by disease associated with this gene.

Methods : Ten retinal dystrophy patients harboring biallelic CDHR1 variants were identified from the National Eye Institute clinic records. Pertinent demographic and historical data as well as genetic testing results were collected. Initial visit and follow-up data were analyzed including visual acuity, color vision, Goldman visual field (GVF) testing, color fundus photography (CFP), fundus autofluorescence (FAF), optical coherence tomography (OCT), electroretinography (ERG).

Results : Six males and four females (mean age at the most recent clinic visit 49.0 ± 13.7 years) from nine families of African American, Asian, and European (including Greek) origins were identified. Age at the time of initial symptoms showed a bimodal distribution with peaks in the second (for RP patients) and fifth (for CRD patients) decades of life. Vision loss was the most common presenting symptom. Best corrected visual acuity at last visit ranged from 20/20 to 20/2000 (average LogMAR 0.8 or 20/125). Notable asymmetry of the degree of macular atrophy was present in two patients. Color vision deficits were more severe in patients with larger areas of macular atrophy. GVF testing revealed constriction of visual fields in three patients diagnosed with RP, while seven patients with maculopathy or CRD had central scotoma that mirrored the degree of macular atrophy. Macular involvement was noted in all patients on CFP, FAF, and OCT. Unrecordable scotopic ERG responses distinguished the RP patients. Novel pathogenic variants included a 7-bp deletion common to three patients of Greek origin.

Conclusions : Despite the variable phenotype of CDHR1-associated retinal dystrophies, an involvement of the macula is a common manifestation in this patient cohort. Notable asymmetry in macular involvement is highlighted in two patients. Novel mutations affecting patients of African American and Greek background are reported.

This is a 2021 ARVO Annual Meeting abstract.