Journal article
Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging
British journal of ophthalmology, Vol.102(1), pp.136-141
01/2018
DOI: 10.1136/bjophthalmol-2017-310498
PMCID: PMC5754866
PMID: 29074494
Abstract
Several genes causing autosomal-dominant cone-rod dystrophy (AD-CRD) have been identified. However, the mechanisms by which genetic mutations lead to cellular loss in human disease remain poorly understood. Here we combine genotyping with high-resolution adaptive optics retinal imaging to elucidate the retinal phenotype at a cellular level in patients with AD-CRD harbouring a defect in the gene. Nine affected members of a four-generation AD-CRD pedigree and three unaffected first-degree relatives underwent clinical examinations including visual acuity, fundus examination, Goldmann perimetry, spectral domain optical coherence tomography and electroretinography. Genome-wide scan followed by bidirectional sequencing was performed on all affected participants. High-resolution imaging using a custom adaptive optics scanning light ophthalmoscope (AOSLO) was performed for selected participants. Clinical evaluations showed a range of disease severity from normal fundus appearance in teenaged patients to pronounced macular atrophy in older patients. Molecular genetic testing showed a mutation in in segregating with disease. AOSLO imaging revealed that of the two teenage patients with mild disease, one had severe disruption of the photoreceptor mosaic while the other had a normal cone mosaic. AOSLO imaging demonstrated variability in the pattern of cone and rod cell loss between two teenage cousins with early AD-CRD, who had similar clinical features and had the identical disease-causing mutation in . This finding suggests that a mutation in does not lead to the same degree of AD-CRD in all patients. Modifying factors may mitigate or augment disease severity, leading to different retinal cellular phenotypes.
Details
- Title: Subtitle
- Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging
- Creators
- Hongxin Song - University of RochesterEthan A Rossi - Department of Ophthalmology, Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USAEdwin Stone - Department of Ophthalmology andVisual Sciences, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USALisa Latchney - University of Rochester, Flaum Eye Institute, Rochester, New York, USADavid Williams - University of RochesterAlfredo Dubra - Department of Ophthalmology, Stanford University, Palo Alto, California, USAMina Chung - University of Rochester, Flaum Eye Institute, Rochester, New York, USA
- Resource Type
- Journal article
- Publication Details
- British journal of ophthalmology, Vol.102(1), pp.136-141
- DOI
- 10.1136/bjophthalmol-2017-310498
- PMID
- 29074494
- PMCID
- PMC5754866
- NLM abbreviation
- Br J Ophthalmol
- ISSN
- 0007-1161
- eISSN
- 1468-2079
- Publisher
- England
- Grant note
- R01 EY004367 / NEI NIH HHS R01 EY014375 / NEI NIH HHS F32 EY021669 / NEI NIH HHS R01 EY021786 / NEI NIH HHS P30 EY001319 / NEI NIH HHS
- Language
- English
- Date published
- 01/2018
- Academic Unit
- Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980094402771
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