The Cone Photoreceptor Mosaic in Aniridia: Within-Family Phenotype-Genotype Discordance.
Adolescent
Adult
Aged
Aniridia
/ diagnosis
Case-Control Studies
Cell Count
DNA
/ genetics
DNA Mutational Analysis
Female
Gene Deletion
Genotype
Humans
Male
Middle Aged
Ophthalmoscopy
PAX6 Transcription Factor
/ genetics
Phenotype
Retinal Cone Photoreceptor Cells
/ metabolism
Tomography, Optical Coherence
/ methods
Visual Acuity
Young Adult
Journal
Ophthalmology. Retina
ISSN: 2468-6530
Titre abrégé: Ophthalmol Retina
Pays: United States
ID NLM: 101695048
Informations de publication
Date de publication:
06 2019
06 2019
Historique:
received:
19
09
2018
revised:
30
01
2019
accepted:
30
01
2019
entrez:
9
6
2019
pubmed:
9
6
2019
medline:
23
1
2020
Statut:
ppublish
Résumé
Investigate in vivo cone photoreceptor structure in familial aniridia caused by deletion in the PAX6 gene to elucidate the complexity of between-individual variation in retinal phenotype. Descriptive case-control study. Eight persons with congenital aniridia (40-66 yrs) from 1 family and 33 normal control participants (14-69 yrs), including 7 unaffected family members (14-53 yrs). DNA was isolated from saliva samples and used in polymerase chain reaction analysis to amplify and sequence exons and intron or exon junctions of the PAX6 gene. High-resolution retinal images were acquired with OCT and adaptive optics scanning light ophthalmoscopy. Cone density (CD; in cones per square millimeter) and mosaic regularity were estimated along nasal-temporal meridians within the central 0° to 5° eccentricity. Horizontal spectral-domain OCT line scans were segmented to analyze the severity of foveal hypoplasia (FH) and to measure retinal layer thicknesses. Within-family variability in macular retinal layer thicknesses, cone photoreceptor density, and mosaic regularity in aniridia compared with normal control participants. DNA sequencing revealed a known PAX6 mutation (IV2-2delA). Those with aniridia showed variable iris phenotype ranging from almost normal appearance to no iris. Four participants with aniridia demonstrated FH grade 2, 2 demonstrated grade 3 FH, and 1 demonstrated grade 4 FH. Visual acuity ranged from 0.20 to 0.86 logarithm of the minimum angle of resolution. Adaptive optics scanning light ophthalmoscopy images were acquired from 5 family members with aniridia. Foveal CD varied between 19 899 and 55 128 cones/mm The results showed considerable variability in foveal development within a family carrying the same PAX6 mutation. This, together with the structural and functional variability within each grade of foveal hypoplasia, underlines the importance of advancing knowledge about retinal cellular phenotype in aniridia.
Identifiants
pubmed: 31174676
pii: S2468-6530(18)30702-4
doi: 10.1016/j.oret.2019.01.020
pmc: PMC6557282
mid: NIHMS1010878
pii:
doi:
Substances chimiques
PAX6 Transcription Factor
0
PAX6 protein, human
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
523-534Subventions
Organisme : NEI NIH HHS
ID : P30 EY001730
Pays : United States
Informations de copyright
Copyright © 2019 American Academy of Ophthalmology. All rights reserved.
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