Restricted Disease in a Family With Autosomal Dominant Rod-Cone Dystrophy Carrying a Novel RHO Mutation

Abstract

Purpose: : To report the phenotype/genotype correlation of a French family with autosomal dominant retinal dystrophy due to a novel rhodopsin mutation.

Methods: : Detailed phenotypic characterization is performed on affected family members spanning 4 generations including precise family history, best corrected visual acuity, slit lamp examination, kinetic and static perimetry, full field and multifocal ERG according to ISCEV standards, fundus autofluorescence imaging and OCT. For genetic diagnosis, the coding exons and flanking regions of RHO are PCR amplified and sequenced. Segregation analysis is performed over 4 generations.

Results: : Onset of symptoms appears in the mid-thirties in this family with moderate night blindness and asymmetric visual loss. Affected family members show patchy area of chorioretinal atrophy with moderate decrease in ERG amplitudes for both scotopic and photopic responses but no implicit time shift consistent with restricted disease. A novel rhodopsin mutation c.620T>A leading to a p.Met207Lys substitution is identified, which co-segregates over 4 generations in this family with the phenotype and is not found in 548 control alleles.

Conclusions: : Restricted chorioretinal degeneration is associated with a novel rhodopsin mutation in the French family presented herein. Farrar et al. in 1992 reported a mutation at the same location but with a different amino-acid change (p.Met207Arg) in an autosomal dominant retinitis pigmentosa family. In this case affected patients showed early onset of symptoms and diffuse rod cone dystrophy. Consequences of this difference in amino-acid substitution upon rhodopsin function will be further discussed to explain differences in phenotypes.

Keywords: genetics • retinal degenerations: hereditary • degenerations/dystrophies