An Arg311Gln NR2E3 Mutation in a Family With Classic Goldmann–Favre Syndrome

Abstract

Abstract: : Purpose: To report clinical and molecular genetic studies in a United Arab Emirates (UAE) family with classic Goldmann–Favre syndrome (GFS). Methods:We examined four siblings from a consanguineous UAE family; two were affected with GFS. The patients underwent slit lamp biomicroscopy, indirect ophthalmoscopy, color vision testing, fundus photography, fluorescein angiography (FA), electroretinography (ERG), electrooculography (EOG), and optical coherence tomography (OCT). Blood samples were obtained to study the NR2E3 gene after informed consent was secured. Mutation analysis of the coding regions of the NR2E3 gene were analyzed using automated sequencing methods. Results: The affected siblings were homozygous for a 932 G>A mutation in exon 6 that changes an arginine to a glutamine at position 311 of the NR2E3 protein. One unaffected sibling was a heterozygous carrier of this mutation. Both patients had poor vision and night blindness since very early childhood. Ophthalmoscopy showed macular and peripheral retinoschisis, confirmed by OCT, as well as clumps of pigment and sub–retinal fibrotic changes along the temporal vascular arcades and in the mid–peripheral fundus. ERG responses to low intensity stimuli were nonrecordable, whereas those to high intensity stimuli had abnormally slow waveforms that were not affected by the presence of a steady rod–desensitizing adaptive field. Conclusions: The classic phenotype in this family with GFS is caused by homozygous Arg311Gln mutations. OCT findings are dramatic and helpful in demonstrating the location of retinoschisis within the neurosensory retina.

Keywords: retinal degenerations: hereditary • genetics