Clinical Characterization of RP10 in a Large Family With an Identified (Asp226Asn) IMPDH1 Mutation

Abstract

Abstract: : Purpose: To evaluate the clinical features associated with the RP10 form of autosomal dominant retinitis pigmentosa (adRP) in individuals with a defined IMPDH1 mutation. Methods: Affected (n=11; 13–60 yrs) and unaffected individuals (n=2; 16 & 24 yrs) from a large family with an Asp226Asn missense mutation were examined. Visual function assessment included visual acuity, color vision, visual field (30–2), dark adaptometry, dark–adapted full–field electroretinography (ffERG), multifocal electroretinography (mfERG), fundus photography, optical coherence tomography (OCT), and a routine ophthalmologic examination. Blood samples were obtained from all participants for basic immune function screening. Patients were divided into two groups based on age for data analysis: teens (n=4; 13–19 yrs) and adults (n=7; ≥20 yrs). Results: Visual acuity was reduced at an early age; affected teens had acuities of 20/32 to 20/100. Visual fields were also markedly constricted (mean=38 degrees) and dark–adapted thresholds were elevated 1.1 log units on average. Visual fields were progressively constricted with age resulting in field ≤20 degrees by age 40 and ≤10 degrees by age 60; dark–adapted thresholds exhibited further elevation (adult mean=1.8 log units). ffERGs were typical of severe RP and included low or non–detectable rod ERGs by age 20 and greater rod than cone loss at all ages. Additional ERG findings in this family were normal to significantly delayed ffERG cone b–wave implicit times that corresponded with implicit times of mfERG responses from the macula. Color defects were observed in 3 individuals (1 teen, 2 adults). OCT revealed foveal swelling in the majority of eyes and cystoid macular edema was diagnosed in 3 individuals. No unusual immunologic findings were noted. Conclusions: The Asp226Asn mutation is associated with a relatively severe, early onset form of retinal degeneration in this family. Visual function measures illustrate significant visual impairment by 20 years of age.

Keywords: retinal degenerations: hereditary • mutations • electroretinography: clinical