CEP290 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Centrosomal protein 290-KD
  • Expressed in ciliated cells throughout the body including the photoreceptor connecting cilium
  • Cilium formation and intracellular protein trafficking
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
Signs for LCA
  • Profound visual loss
  • Pendular nystagmus
  • Photophobia
  • Oculodigital sign
  • Keratoconus
  • Cataract
  • Normal fundal appearance or peripheral white flecks (younger patients)
  • Progressive retinal pigmentation and RPE atrophy
  • Coats’ like vasculopathy or chorioretinal coloboma are rare presentations
Visual function
  • Majority have VA 6/60 or worse at presentation
  • VA tends to remain stable over time
Systemic featuresJoubert syndrome 5
  • Neurological (hypotonia, ataxia, oculomotor apraxia)
  • Cerebellar vermis hypoplasia giving rise to the characteristic “molar tooth sign” on MRI
  • Psychomotor delay
  • Usually associated with juvenile nephronophthisis with CEP290 mutations
Senior-Loken syndrome 6
  • Juvenile nephronophthisis
  • Absence of neurologic/neuroradiologic features of Joubert syndrome
Bardet-Biedl syndrome

Meckel syndrome 4
  • Renal cysts
  • Occipital encephalocele
  • Hepatic ductal dysplasia and cysts
  • Post-axial polydactyly
  • Pre- or perinatal lethality
Key investigations
  • ERG: extinguished rod and cone responses
  • FAF: Central hyper-AF ring with peripheral hypo-AF
  • OCT: Preserved foveal outer retinal layers till the 4th decade before degenerating slowly; early parafoveal outer retinal loss
  • MRI brain and orbit
  • Renal ultrasound
  • Systemic assessment with a paediatrician and other relevant specialists
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
Further information

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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]

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Multimodal imaging

Multimodal imaging of a 34 year old man with CEP290-LCA. Colour fundus photograph (A) shows some bone-spicule RPE hyperpigmentation and retinal atrophy in the mid-periphery. FAF (B) shows a central hyper-AF ring and the posterior pole has normal AF. There is hypo-AF with discrete areas of RPE atrophy in the periphery. OCT of the macula (C) shows preserved outer retinal layers centrally and atrophy with increasing eccentricity.

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  1.  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
  2.  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
  3.  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
  4.  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
  5.  Cideciyan AV, Jacobson SG. Leber Congenital Amaurosis (LCA): Potential for Improvement of Vision. Invest Ophthalmol Vis Sci. 2019;60(5):1680-1695
  6.  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
  7.  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
  8.  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
  9.  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
  10.  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
  11.  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
  12.  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

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Updated on November 30, 2020

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