A detailed phenotypic description of autosomal dominant cone dystrophy due to a de novo mutation in the GUCY2D gene.
OBJECTIVE
The purpose of this study is to describe the phenotype of a family with de novo mutation in the GUCY2D.


METHODS
Five subjects, including two monozygotic twins, underwent ophthalmic clinical examination while some had autofluorescence imaging (AF) and optical coherence tomography (OCT). Symptomatic individuals underwent electrophysiological testing. The youngest subject (21 years) was also evaluated psychophysically. DNA obtained from the individuals was screened for mutations in GUCY2D. Microsatellite markers were used to determine the haplotype of 17p surrounding the GUCY2D gene.


RESULTS
The youngest subject had 6/18 visual acuity, an annulus of hyper-autofluorescence in the perifoveal region, and a subfoveal absence of outer segments on OCT. In the older individuals, severe thinning of inner retina and a patchy loss of photoreceptors and retinal pigment epithelium were observed in the perifoveal region. All three showed generalised cone system dysfunction with preserved rod function on electrophysiology. Psychophysical evaluation was consistent with poor cone function. Screening of the GUCY2D gene revealed the mutation p.R838H in all the affected individuals and was absent in the asymptomatic patients. Haplotyping showed that the mutation originated from the unaffected mother.


CONCLUSIONS
Autosomal dominant cone dystrophy due to GUCY2D can occur without a history in the antecedents due to a de novo mutation. This is important to consider in any simplex case with a similar phenotype. The phenotype description of this disorder is expanded with detailed description of the OCT findings. This paper describes the concordance of the phenotypic findings in the monozygotic twins.
1] Moorfields Eye Hospital NHS Foundation Trust, London, UK [2] Institute of Ophthalmology, University College London London, UK.
R
R
Mukherjee
1] Moorfields Eye Hospital NHS Foundation Trust, London, UK [2] Institute of Ophthalmology, University College London London, UK.
A G
AG
Robson
1] Moorfields Eye Hospital NHS Foundation Trust, London, UK [2] Institute of Ophthalmology, University College London London, UK.
G E
GE
Holder
Institute of Ophthalmology, University College London London, UK.
A
A
Stockman
1] Moorfields Eye Hospital NHS Foundation Trust, London, UK [2] Institute of Ophthalmology, University College London London, UK.
C A
CA
Egan
1] Moorfields Eye Hospital NHS Foundation Trust, London, UK [2] Institute of Ophthalmology, University College London London, UK.
A T
AT
Moore
1] Moorfields Eye Hospital NHS Foundation Trust, London, UK [2] Institute of Ophthalmology, University College London London, UK.
A R
AR
Webster
D000328:Adult; D000368:Aged; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D006162:Guanylate Cyclase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate; D011601:Psychophysics; D011956:Receptors, Cell Surface / Q000235:genetics*; D017949:Retinal Cone Photoreceptor Cells / Q000473:pathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D041623:Tomography, Optical Coherence; D014792:Visual Acuity; D055815:Young Adult
D011956:Receptors, Cell Surface; C110715:guanylate cyclase 1; D006162:Guanylate Cyclase