Abstract
Purpose :
The purpose of this paper is to describe the clinical features and molecular genetic findings of patients from three independent families with autosomal dominant cone dystrophy.
Methods :
The clinical evaluation of the patients included visual acuity test, dilated funduscopy, optical coherence tomography (OCT), autofluorescein imaging (FAF) and Ganzfeld electroretinography (GfERG). Detailed pedigrees were obtained. Whole exome sequencing (WES) was carried out in the index patients, and a targeted panel of 316 genes was analyzed. The identified mutations were confirmed, and the other family members were evaluated using Sanger sequencing.
Results :
All patients were presented with reduced visual acuity. Funduscopy showed pigmentary changes of the macular area. OCT images showed thinning of the outer layers of the retina with disruption of the ellipsoid zone in the central macular region. Nummular hyper/hypoautofluorescence pattern was shown on FAF imaging. Genetic testing has identified the same heterozygous variant, c.305A>G, leading to amino acid change in the GUCA1A gene in all of these patients.
Conclusions :
Imaging and electrophysiological characteristics showed cone dystrophy in three patients from independent families from the southwestern part of Hungary. The identified genetic variant, c.305A>G, (p.Asp102Gly) in GUCA1A, a gene known to be disease-causing in autosomal dominant cone/cone-rod dystrophy was not previously described and is absent in the major reference population databases. Based on ACMG classification and in silico tools, it is regarded as a likely pathogenic variant. Segregation analysis in some other family members confirms the pathogenicity of this variant, causing autosomal dominant cone dystrophy.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.