Progressive cone dystrophy with deutan genotype and phenotype

Abstract

To study the electroretinographic signals originating in the long-wavelength-sensitive (L) and middle-wavelength-sensitive (M) cone pathways by means of large-field and multifocal cone type-specific electroretinograms (ERGs) in a patient with progressive cone dystrophy. A 65-year-old male patient with colour vision disturbances (age at onset 10 years), loss of visual acuity (14 years), and central visual field defects (40 years) was investigated. Large-field flicker-ERG responses to stimuli that exclusively modulated the L-cones or the M-cones, or the two simultaneously (both in-phase and in counter-phase), were measured. Short-wavelength-sensitive (S) cones were not modulated. Multifocal ERGs (mfERGs) were also recorded, with a pattern-reversing display that modulated only the L- or the M-cones at equal cone contrasts and average quantal catches. Genetic analysis of L- and M-pigment genes was performed on genomic DNA isolated from peripheral venous blood. The patient showed a normal rod-driven ERG but reduced cone-driven electroretinographic amplitudes with normal implicit times in the International Society for Clinical Electrophysiology of Vision (ISCEV) standard ERG. The large-field flicker-ERG responses to pure L-cone modulation were significantly above noise level but were substantially reduced in comparison with both normal trichromatic subjects and (otherwise normal) deuteranopes. The L-cone driven electroretinographic implicit times and phases were within normal limits. The M-cone driven electroretinographic responses were not detectable. A model fit of all the L- and M-cone driven flicker-ERG data revealed that the responses were exclusively driven by the L-cones. Consistently, the cone type-specific mfERGs showed severely reduced but detectable responses to L-cone-isolating stimuli. The M-cone driven multifocal-ERG responses were undistinguishable from noise. The L- and M-pigment gene array consisted of only a single L-pigment gene. The complete coding sequence of this gene was determined and showed no abnormality. This patient exhibits a coincidence of progressive cone dystrophy and deuteranopia. The molecular genetic data of the L/M-pigment gene array is consistent with the deutan phenotype. It cannot be excluded that the rearrangement of the X-chromosome pigment gene array is responsible for the cone dystrophy in this patient. It is, however, suggested that the dichromacy and the cone dystrophy have different and independent genetic origins.