Three Novel Peripherin/RDS Mutations Associated With Pattern Dystrophy

Abstract

Purpose:: Phenotype genotype correlation in three novel peripherin/RDS mutations

Methods:: Phenotypic characterisation including symptoms, fundus findings, autofluorescence and optical coherence tomography imaging and electrophysiology of three unrelated probands was carried out. Mutational screening for the peripherin/RDS gene was performed using standard protocols.

Results:: One patient (I ) a mutation was identified in a highly conserved region of coding DNA resulting in a six amino acid sequence change (pGly202-Asp207del6). This was associated with a pattern dystrophy phenotype. In the other two patients mutations resulted in two different frameshift mutations leading to a premature termination codon. In patient II (c259-266del8) a much severer phenotype was noted characterised by pseudofundus flavimaculatus with severe abnormalities of the rod amplitudes and implicit times on electrophysiology testing with no electro-oculogram light rise. An insertion (c.707dupA) in exon 2 was identified in patient (III) and was associated with a pseudofundus flavimaculatus phenotype, with mild rod abnormalities affecting amplitudes and implicit times, and a subnormal EOG light rise.

Conclusions:: This case series presents three novel mutations of the peripherin/RDS gene associated with pattern dystrophy/pseudofundus flavimaculatus, and in one case quite severe rod involvement. There is a wide variation in phenotypic expressivity associated with the peripherin RDS gene, which seems to depend on the type of mutation its location in the protein structure. Identification of a familial mutation allows for the possibility of predictive genetic testing for adult members of the family in which the mutation is identified.

Keywords: retinal degenerations: hereditary • gene screening • inner retina dysfunction: hereditary