AIPL1 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: Aryl-hydrocarbon-interacting-protein-like 1
  • Photoreceptor development
  • Involved in the assembly of a key enzyme in the phototransduction cascade (PDE6)
Clinical phenotype
(OMIM phenotype no.)
  • Autosomal recessive
  • Autosomal dominant
Signs for LCA/EOSRD
  • Early onset severe visual loss
  • Pendular nystagmus
  • Oculodigital sign
  • Keratoconus
  • Cataracts
  • Fundus usually appears normal during infancy
  • Progressive pigmentary retinopathy in the mid-periphery
  • Progressive maculopathies, ranging from mild foveal pigmentary changes and bull’s eye lesion to full thickness atrophy
Visual function
  • Majority have PL vision (6/48 to NPL) which progressively worsens
Systemic features
  • No extraocular anomalies reported
Key investigations
  • ERG: absent responses/severe cone-rod dystrophy that worsens over time
  • FAF: Mottled AF in the posterior pole with absent AF in atrophic areas
  • OCT: Relative preservation of foveal outer retinal layers before 4 years of age; progressive foveal ONL thinning thereafter with increased inner retinal thickness and disorganized lamination
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal)
  • Whole exome sequencing
  • Whole genome sequencing
Therapies under research
  • None at present
Further information

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Additional information

Majority of AIPL1 mutations manifest as autosomal recessive Leber Congenital Amaurosis (LCA). However, a heterozygous variant involving a 12-base pair deletion were detected in two patients diagnosed as cone-rod dystrophy and juvenile-onset retinitis pigmentosa (RP). No further phenotypic detail was provided.[1]

Another patient with biallelic variants was diagnosed as RP at the age of 14 after presenting with reduced VA, nyctalopia and peripheral VF loss from the first decade of life. At age 45, there was equal loss of cone and rod ERG signals and he had a typical RP fundal phenotype. A small central island of VF was preserved till he was 67.

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  1.  Sohocki MM, Perrault I, Leroy BP, et al. Prevalence of AIPL1 mutations in inherited retinal degenerative disease. Mol Genet Metab. 2000;70(2):142-150
  2.  Jacobson SG, Cideciyan AV, Aleman TS, et al. Human Retinal Disease from AIPL1 Gene Mutations: Foveal Cone Loss with Minimal Macular Photoreceptors and Rod Function Remaining. Investigative Ophthalmology & Visual Science. 2011;52(1):70-79
  3.  Kolandaivelu S, Ramamurthy V. AIPL1 protein and its indispensable role in cone photoreceptor function and survival. Adv Exp Med Biol. 2014;801:43-48
  4.  van der Spuy J, Kim JH, Yu YS, et al. The expression of the Leber congenital amaurosis protein AIPL1 coincides with rod and cone photoreceptor development. Invest Ophthalmol Vis Sci. 2003;44(12):5396-5403
  5.  Tan MH, Mackay DS, Cowing J, et al. Leber congenital amaurosis associated with AIPL1: challenges in ascribing disease causation, clinical findings, and implications for gene therapy. PLoS One. 2012;7(3):e32330
  6.  Aboshiha J, Dubis AM, van der Spuy J, et al. Preserved outer retina in AIPL1 Leber’s congenital amaurosis: implications for gene therapy. Ophthalmology. 2015;122(4):862-864
  7.  Pennesi ME, Stover NB, Stone EM, Chiang PW, Weleber RG. Residual electroretinograms in young Leber congenital amaurosis patients with mutations of AIPL1. Invest Ophthalmol Vis Sci. 2011;52(11):8166-8173
  8.  Testa F, Surace EM, Rossi S, et al. Evaluation of Italian patients with leber congenital amaurosis due to AIPL1 mutations highlights the potential applicability of gene therapy. Invest Ophthalmol Vis Sci. 2011;52(8):5618-5624
  9.  Xu K, Xie Y, Sun T, Zhang X, Chen C, Li Y. Genetic and clinical findings in a Chinese cohort with Leber congenital amaurosis and early onset severe retinal dystrophy. Br J Ophthalmol. 2019

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Updated on November 30, 2020
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