Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging
| العنوان: | Phenotypic diversity in autosomal-dominant cone-rod dystrophy elucidated by adaptive optics retinal imaging |
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| المؤلفون: | Edwin M. Stone, Mina M. Chung, Hongxin Song, David R. Williams, Ethan A. Rossi, Lisa R. Latchney, Alfredo Dubra |
| المصدر: | The British Journal of Ophthalmology |
| بيانات النشر: | BMJ, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, retina, Optics and Photonics, Pathology, Visual acuity, genetic structures, Visual Acuity, degeneration, Fundus (eye), medicine.disease_cause, chemistry.chemical_compound, 0302 clinical medicine, Medicine, genetics, Rod cell, Fluorescein Angiography, Child, Mutation, medicine.diagnostic_test, imaging, Equipment Design, Middle Aged, Sensory Systems, Pedigree, Phenotype, medicine.anatomical_structure, dystrophy, Female, medicine.symptom, Tomography, Optical Coherence, Adult, medicine.medical_specialty, Adolescent, Genotype, Fundus Oculi, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, Electroretinography, Humans, Aged, Retina, business.industry, Dystrophy, Retinal, eye diseases, Laboratory Science, Ophthalmology, 030104 developmental biology, chemistry, 030221 ophthalmology & optometry, sense organs, business, Cone-Rod Dystrophies |
| الوصف: | PurposeSeveral 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 GUCA1A gene.MethodsNine 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.ResultsClinical 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 GUCA1A 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.ConclusionsAOSLO 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 GUCA1A. This finding suggests that a mutation in GUCA1A 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. |
| تدمد: | 1468-2079 0007-1161 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b466164deecfa68b0df015a4f02fb68bTest https://doi.org/10.1136/bjophthalmol-2017-310498Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b466164deecfa68b0df015a4f02fb68b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682079 00071161 |
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