CERKL Mutations Cause Retina-Wide Cone and Rod Disease With Prominent Maculopathy

Abstract

Purpose: : To define the phenotype of the retinal degeneration associated with mutations in the CERKL gene.

Methods: : Simplex and multiplex patients (ages 26-54) from unrelated families with a mutation in CERKL (R257X) were evaluated by ocular examination, kinetic and chromatic static perimetry, optical coherence tomography (OCT) and electroretinography (ERG).

Results: : Patients showed a spectrum of disease expression: from mild visual acuity loss to light perception; from a full kinetic field with relative central scotomas to remnant peripheral islands of function; from about 50% reduction of rod and cone ERG waveforms to non-detectable signals. Chromatic perimetry showed large central rod and cone scotomas; residual foveal islands of abnormal cone function could be present and supported the better acuities and central fixation. Peripheral rod and cone function was generally less affected than central function. OCT showed a small foveal island of outer nuclear layer (ONL) in those with preserved acuity and foveal fixation. Eccentric to an annular region of no discernible ONL, there was a measurable ONL in the near mid-periphery. Evidence of inner retinal remodeling was present in areas of ONL loss.

Conclusions: : CERKL mutations are associated with a widespread retinal degeneration of varying disease severity and macular vision loss. The disease expression first identified to be associated with CERKL (R257X) mutations was RP26, an autosomal recessive form of RP. The current subset of patients with the same mutation had a phenotype reminiscent of the cone-rod dystrophies (CRD), suggesting that CERKL should be considered among the molecular causes of CRD.

Keywords: retinal degenerations: hereditary