title: GUCY2D- or GUCA1A-related autosomal dominant cone-rod dystrophy: is there a phenotypic difference?
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: *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.
authors.forename: Ditta
authors.initials: D
authors.lastname: Zobor
authors.forename: Eberhart
authors.initials: E
authors.lastname: Zrenner
authors.forename: Bernd
authors.initials: B
authors.lastname: Wissinger
authors.forename: Susanne
authors.initials: S
authors.lastname: Kohl
authors.forename: Herbert
authors.initials: H
authors.lastname: Jägle
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D003623:Dark Adaptation / Q000502:physiology; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005799:Genes, Dominant; D056726:Genetic Association Studies; D006162:Guanylate Cyclase / Q000235:genetics*; D051604:Guanylate Cyclase-Activating Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology
chemical_list: C496736:GUCA1A protein, human; D051604:Guanylate Cyclase-Activating Proteins; D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase