Overview
Gene (OMIM No.) |
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Function of gene/protein |
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Clinical phenotype (OMIM phenotype no.) | |
Inheritance |
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Signs for LCA |
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Visual function |
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Systemic features | Joubert syndrome 5
Meckel syndrome 4
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Key investigations |
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Molecular diagnosis | Next generation sequencing
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Management | OcularSystemic
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Therapies under research |
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Further information |
Additional information
Mutations in CEP290 account for 15-20% of LCA/EOSRD cases. The most common mutation in Europe and the US is the c.2991+1655 A>G splice-site mutation in intron 26, which introduces a pseudo-exon with a premature stop codon to about 50–75% of the CEP290 mRNA transcripts. The phenotype of this specific mutation tends to be only limited to the eye.[1],[2]
Multimodal imaging

References
- den Hollander AI, Koenekoop RK, Yzer S, et al. Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis. Am J Hum Genet. 2006;79(3):556-561
- Perrault I, Delphin N, Hanein S, et al. Spectrum of NPHP6/CEP290 mutations in Leber congenital amaurosis and delineation of the associated phenotype. Hum Mutat. 2007;28(4):416
- Sheck L, Davies WIL, Moradi P, et al. Leber Congenital Amaurosis Associated with Mutations in CEP290, Clinical Phenotype, and Natural History in Preparation for Trials of Novel Therapies. Ophthalmology. 2018;125(6):894-903
- McAnany JJ, Genead MA, Walia S, et al. Visual acuity changes in patients with leber congenital amaurosis and mutations in CEP290. JAMA Ophthalmol. 2013;131(2):178-182
- Cideciyan AV, Jacobson SG. Leber Congenital Amaurosis (LCA): Potential for Improvement of Vision. Invest Ophthalmol Vis Sci. 2019;60(5):1680-1695
- Feldhaus B, Weisschuh N, Nasser F, et al. CEP290 mutation spectrum and delineation of the associated phenotype in a large German cohort: a monocentric study. Am J Ophthalmol. 2019
- Valkenburg D, van Cauwenbergh C, Lorenz B, et al. Clinical Characterization of 66 Patients With Congenital Retinal Disease Due to the Deep-Intronic c.2991+1655A>G Mutation in CEP290. Invest Ophthalmol Vis Sci. 2018;59(11):4384-4391
- Brancati F, Barrano G, Silhavy JL, et al. CEP290 mutations are frequently identified in the oculo-renal form of Joubert syndrome-related disorders. Am J Hum Genet. 2007;81(1):104-113
- Valente EM, Silhavy JL, Brancati F, et al. Mutations in CEP290, which encodes a centrosomal protein, cause pleiotropic forms of Joubert syndrome. Nat Genet. 2006;38(6):623-625
- Leitch CC, Zaghloul NA, Davis EE, et al. Hypomorphic mutations in syndromic encephalocele genes are associated with Bardet-Biedl syndrome. Nat Genet. 2008;40(4):443-448
- Frank V, den Hollander AI, Brüchle NO, et al. Mutations of the CEP290 gene encoding a centrosomal protein cause Meckel-Gruber syndrome. Human Mutation. 2008;29(1):45-52
- Helou J, Otto EA, Attanasio M, et al. Mutation analysis of NPHP6/CEP290 in patients with Joubert syndrome and Senior-Løken syndrome. J Med Genet. 2007;44(10):657-663