Purpose: To compare the phenotype of patients with heterozygous mutation in GUCY2D or GUCA1A causing autosomal dominant cone or cone–rod dystrophies.
Methods: Five patients from one family with GUCA1A and nine patients from four families with GUCY2D mutations were included. Psychophysical and electrophysiological examinations were performed to study retinal function. Fundus autofluorescence imaging and spectral domain optical coherence tomography were performed for morphologic characterization.
Results: Genetic analysis revealed the mutation c.451C>T (p.L151F) in the GUCA1A family. In the GUCY2D group, c.2512C>T (p.R838C) was the most frequent (2 families), c.2512C>G (p.R838G) and c.2513G>A (p.R838H) were found in one family each. Visual acuity was reduced to 0.04 to 0.7 in GUCA1A and to 0.014 to 0.5 in patients with GUCY2D. Dark adaptation showed elevated thresholds in the GUCY2D group. Scotopic electroretinography revealed a tendency to a more affected rod function in the GUCY2D group. Photopic electroretinography showed residual or absent responses in both groups. Fundus alterations were confined to the macula in both groups.
Conclusion: GUCA1A and GUCY2D mutations are both accompanied by similar pattern of generalized cone dysfunction with a tendency to less involvement of the rod photoreceptors and a less severe phenotype in patients with GUCA1A.
Heterozygous mutations of the GUCY2D (encoding retGC-1) and GUCA1A genes (encoding GCAP1) are known to cause autosomal dominant cone and cone–rod dystrophies. In this study, a tendency to a less severe phenotype and less involvement of the rod photoreceptors in patients with GUCA1A despite the similar pathophysiological background was observed.
*Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany;
†Molecular Genetics Laboratory, Institute for Ophthalmic Research, University of Tübingen, Tübingen, Germany;
‡Department of Ophthalmology, University of Regensburg, Regensburg, Germany; and
¶Werner Reichardt Centre for Integrative Neuroscience (CIN), University of Tübingen, Tübingen, Germany.
Reprint requests: Ditta Zobor, MD, Institute for Ophthalmic Research, University of Tübingen, Schleichstrasse 12-16, Tübingen 72076, Germany; e-mail: firstname.lastname@example.org
Supported by a personal grant of the Kerstan Foundation to D. Zobor and a grant KFO134-Ko2176/1-2 to S. Kohl.
This work was supported by a grant of the BMBF (O1GM1108A) to BW, SK and EZ and of Deutsche Forschungsgemeinschaft (EXC307, CIN) to EZ.
None of the authors have any conflicting interests to disclose.