Tags

Type your tag names separated by a space and hit enter

Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis.
Hum Mutat 2007; 28(11):1074-83HM

Abstract

Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with Joubert syndrome and are the most common cause of the childhood recessive blindness known as Leber congenital amaurosis (LCA). An in-frame deletion in Cep290 shows rapid degeneration in the rod-rich mouse retina. To explore the mechanisms of the human retinal disease, we studied CEP290-LCA in patients of different ages (7-48 years) and compared results to Cep290-mutant mice. Unexpectedly, blind CEP290-mutant human retinas retained photoreceptor and inner laminar architecture in the cone-rich central retina, independent of severity of visual loss. Surrounding the cone-rich island was photoreceptor loss and distorted retina, suggesting neural-glial remodeling. The mutant mouse retina at 4-6 weeks of age showed similar features of retinal remodeling, with altered neural and synaptic laminae and Muller glial activation. The visual brain pathways in CEP290-LCA were anatomically intact. Our findings of preserved foveal cones and visual brain anatomy in LCA with CEP290 mutations, despite severe blindness and rapid rod cell death, suggest an opportunity for visual restoration of central vision in this common form of inherited blindness.

Authors+Show Affiliations

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. cideciya@mail.med.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17554762

Citation

Cideciyan, Artur V., et al. "Centrosomal-ciliary Gene CEP290/NPHP6 Mutations Result in Blindness With Unexpected Sparing of Photoreceptors and Visual Brain: Implications for Therapy of Leber Congenital Amaurosis." Human Mutation, vol. 28, no. 11, 2007, pp. 1074-83.
Cideciyan AV, Aleman TS, Jacobson SG, et al. Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. Hum Mutat. 2007;28(11):1074-83.
Cideciyan, A. V., Aleman, T. S., Jacobson, S. G., Khanna, H., Sumaroka, A., Aguirre, G. K., ... Swaroop, A. (2007). Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. Human Mutation, 28(11), pp. 1074-83.
Cideciyan AV, et al. Centrosomal-ciliary Gene CEP290/NPHP6 Mutations Result in Blindness With Unexpected Sparing of Photoreceptors and Visual Brain: Implications for Therapy of Leber Congenital Amaurosis. Hum Mutat. 2007;28(11):1074-83. PubMed PMID: 17554762.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Centrosomal-ciliary gene CEP290/NPHP6 mutations result in blindness with unexpected sparing of photoreceptors and visual brain: implications for therapy of Leber congenital amaurosis. AU - Cideciyan,Artur V, AU - Aleman,Tomas S, AU - Jacobson,Samuel G, AU - Khanna,Hemant, AU - Sumaroka,Alexander, AU - Aguirre,Geoffrey K, AU - Schwartz,Sharon B, AU - Windsor,Elizabeth A M, AU - He,Shirley, AU - Chang,Bo, AU - Stone,Edwin M, AU - Swaroop,Anand, PY - 2007/6/8/pubmed PY - 2007/11/14/medline PY - 2007/6/8/entrez SP - 1074 EP - 83 JF - Human mutation JO - Hum. Mutat. VL - 28 IS - 11 N2 - Mutations in the centrosomal-ciliary gene CEP290/NPHP6 are associated with Joubert syndrome and are the most common cause of the childhood recessive blindness known as Leber congenital amaurosis (LCA). An in-frame deletion in Cep290 shows rapid degeneration in the rod-rich mouse retina. To explore the mechanisms of the human retinal disease, we studied CEP290-LCA in patients of different ages (7-48 years) and compared results to Cep290-mutant mice. Unexpectedly, blind CEP290-mutant human retinas retained photoreceptor and inner laminar architecture in the cone-rich central retina, independent of severity of visual loss. Surrounding the cone-rich island was photoreceptor loss and distorted retina, suggesting neural-glial remodeling. The mutant mouse retina at 4-6 weeks of age showed similar features of retinal remodeling, with altered neural and synaptic laminae and Muller glial activation. The visual brain pathways in CEP290-LCA were anatomically intact. Our findings of preserved foveal cones and visual brain anatomy in LCA with CEP290 mutations, despite severe blindness and rapid rod cell death, suggest an opportunity for visual restoration of central vision in this common form of inherited blindness. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/17554762/Centrosomal_ciliary_gene_CEP290/NPHP6_mutations_result_in_blindness_with_unexpected_sparing_of_photoreceptors_and_visual_brain:_implications_for_therapy_of_Leber_congenital_amaurosis_ L2 - https://doi.org/10.1002/humu.20565 DB - PRIME DP - Unbound Medicine ER -