ASSESSMENT OF THE PHENOTYPIC RANGE SEEN IN DOYNE HONEYCOMB RETINAL DYSTROPHY

Objective: Using molecular genetics as the basis for diagnosis, to ass ess the phenotype in the family originally described as having dominan tly inherited Dog ne honeycomb retinal dystrophy (DHRD) linked to chro mosome 2p16. Design: Clinical examination including fluorescein angiog raphy was undertaken in 107 family members. Nine affected patients und erwent electroretinography, perimetry, dark adaptometry, color-contras t sensitivity measurement, and autofluorescent Fundus imaging. Patient s: The disease-associated haplotype used to allocate disease status wa s based on our further refinement of the DHRD locus to between loci D2 S2739 and D2S378. The study identified 50 affected patients. In additi on, previously published information on a further 8 individuals was us ed. The study population represented 6 generations of a 9-generation p edigree. Results: Three types of deposits were seen: large, soft druse n at the macula and abutting the optic nerve head; small, hard deposit s that in some patients radiated from the macula; and autofluorescent deposits. Most younger affected individuals exhibited small hard druse n only at the macula and had normal visual function. Information on 2 patients suggested that DHRD can be a cause of childhood-onset blindne ss. Advanced disease was associated with severe visual loss and poster ior pole atrophy without signs of drusen. Advanced age was not invaria bly associated with severe visual loss. Conclusions: Previously identi fied characteristics of DHRD were confirmed and new features identifie d. Contrary to previous reports, the constancy and severity of radial (basal laminar) drusen seen clinically are the only features that can be used to differentiate between DHRD and malattia leventinese. The hi ghly variable phenotype suggests that the influence of the DHRD-mutant gene mag be modulated by other genetic and/or environmental factors.