Rod and Cone-Mediated Function in Choroideremia Carriers with Mutations in the REP-1 Gene

Abstract

Abstract: : Purpose: To evaluate rod and cone-mediated function in X- linked choroideremia (CHM) carriers with different REP-1 gene mutations and several degrees of fundus abnormalities. Methods: Sixteen CHM female carriers (age range: 11-64 years; V.A.: 0.8-1) underwent to a complete ophthalmologic examination, including Farnsworth D-15 colour test, Goldmann perimetry, Humphrey 10-2 perimetry, Ganzfeld scotopic and photopic ERGs according to ISCEV standards and focal macular ERG (central 12°). Sixteen age-matched control subjects were also tested. Results: Fundus abnormalities included pigmented stippling and focal atrophy of retinal pigmented epithelium in both macula and periphery. When compared to controls, CHM carriers showed, on average, reduced scotopic ERG b-wave amplitude (by 20%, p < 0.01). Photopic and focal ERG amplitudes did not differ between patients and controls. Scotopic and photopic b-wave implicit times of individual patients tended to increase with increasing age, and were altered only in the elder patients. D-15 test was normal in all patients. Goldmann fields were mildly (15°) restricted in five patients. In four patients central perimetric sensitivity was abnormally reduced (p < 0.05). REP-1 gene mutations detected in female carriers were deletions, nonsense mutations, splice-site mutations and frame shift alterations. Conclusions: CHM carriers, independently from age and the type of REP-1 mutations, show losses mainly in the rod-mediated function. Instead, central and peripheral cone-mediated function tends to be more preserved and shows abnormalities only in elder patients. This finding suggests that rod photoreceptors may be the initial site of dysfunction in coroideremia carriers.

Keywords: retinal degenerations: hereditary • electrophysiology: clinical • choroid