Phenotypic characterization of a large family with RP10 autosomal-dominant retinitis pigmentosa: An Asp226Asn mutation in the IMPDH1 gene

• PURPOSE: To evaluate the clinical features associated with the RP10 form of autosomal-dominant retinitis pigmentosa in 11 affected members of various ages from one family with a defined IMPDH1 mutation (Asp226Asn). • DESIGN: Prospective, observational case series. • METHODS: Visual function assessment included visual acuity, color vision, visual field, dark adaptometry, full-field electroretinography (ffERG), and multifocal electroretinography (mfERG). Ophthalmologic examinations, fundus photography, and optical coherence tomographic scans were also performed. Blood samples were obtained to screen for basic immune function. • RESULTS: Visual acuity was slightly reduced in the teenage years and substantially reduced in association with cystoid macular edema (CME) at all ages. Color defects were observed in three patients (one teen, two adults). Dark-adapted thresholds were elevated. Visual fields were markedly constricted by age 40 (≤20 degrees). Rod and cone a-wave and b-wave ffERG responses were small or nondetectable by age 20, with greater rod than cone loss at all ages. The normal to significantly delayed ffERG cone b-wave implicit times in different patients were explained by their mfERG implicit times from the central retina. The amplification factors (log S) and recovery kinetics derived from the full-field rod a-waves were normal. Optical coherence tomography revealed subretinal fluid accumulation in the majority of eyes. Cystoid macular edema was diagnosed in four patients. No unusual immunologic findings were noted. • CONCLUSIONS: The Asp226Asn mutation is associated with a severe, early-onset form of retinal degeneration in members of this family.