A Novel Homozygous RPE65 Mutation in Leber Congenital Amaurosis Associated With Cone-Rod Dystrophy

Détails

ID Serval
serval:BIB_AAEF312C6CE6
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Titre
A Novel Homozygous RPE65 Mutation in Leber Congenital Amaurosis Associated With Cone-Rod Dystrophy
Titre de la conférence
Investigative Ophthalmology and Visual Science
Auteur(s)
Abouzeid H., Othman I.S., Sabry S., Favre I., Herkenne C., Schorderet D.F., Munier F.L.
Organisation
ARVO E-Abstract 3083/A278
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
51
Langue
anglais
Résumé
Purpose: To report the clinical and genetic study of a family with Leber congenital amaurosis (LCA).
Methods: We studied a consanguineous family from Yemen in which three individuals were affected with LCA. Genomic DNA was prepared from venous leukocytes. Linkage analysis of all family members using polymorphic markers flanking the known LCA genes was performed, followed by direct sequencing of all the exons and intron-exon junctions of the RPE65 gene.
Results: The three affected were 5, 8 and 12 years old. Severe visual impairment and night blindness were noticed during infancy. Nystagmus was not a feature. Photophobia was only observed in the 8-year-old patient. The 5-year old youngest affected had a bilateral hyperopia of +3.50 and a visual acuity of 1/60. The oldest two had mild myopia and visual acuity limited to hand movements RE and counting fingers LE for the oldest and of 5/60 OD, 6/60 OS for the other. On fundus examination, they harbored common clinical features such as disc pallor, attenuated vessels, white flecks in the retina mid-periphery and bull's eye maculopathy. Electroretinograms of the oldest child were completely extinguished while residual scotopic responses with abolished photopic and flicker responses were observed in the two youngest. Sequencing identified a novel missense mutation, IVS2-3C>G, in the second RPE65 intron. The mutation was not detected in 80 ethnically matched normal individuals.
Conclusion: We have identified a novel LCA-related homozygous RPE65 mutation associated with a severe clinical presentation including an early and severe cone dysfunction. This is in contrast with the presentation associated with other RPE65 mutations predominantly causing a rod-cone dystrophy with residual cone function. The identified mutation potentially affects splicing of the third exon and could result in a loss of function. Definite functional consequences of this change still need to be characterized.
Création de la notice
17/12/2010 10:27
Dernière modification de la notice
20/08/2019 15:14
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