April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Clinical Spectrum of Patients With AIPL1 Mutations in Recessive Inherited Retinal Dystrophies
Author Affiliations & Notes
  • M. H. Tan
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
    Genetics and Paediatrics,
    Moorfields Eye Hospital, London, United Kingdom
  • H. V. Tran
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
    Genetics and Paediatrics,
    Moorfields Eye Hospital, London, United Kingdom
  • A. J. Smith
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • R. Henderson
    Genetics and Paediatrics,
    Moorfields Eye Hospital, London, United Kingdom
  • I. Russell-Eggitt
    Genetics and Paediatrics,
    Moorfields Eye Hospital, London, United Kingdom
  • A. G. Robson
    Department of Electrodiagnostics,
    Moorfields Eye Hospital, London, United Kingdom
  • A. R. Webster
    Genetics and Paediatrics,
    Moorfields Eye Hospital, London, United Kingdom
  • G. E. Holder
    Department of Electrodiagnostics,
    Moorfields Eye Hospital, London, United Kingdom
  • R. R. Ali
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
    NIHR Biomedical Research Centre for Ophthalmology, London, United Kingdom
  • A. T. Moore
    Genetics and Paediatrics,
    Moorfields Eye Hospital, London, United Kingdom
    NIHR Biomedical Research Centre for Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  M.H. Tan, None; H.V. Tran, None; A.J. Smith, None; R. Henderson, None; I. Russell-Eggitt, None; A.G. Robson, None; A.R. Webster, None; G.E. Holder, None; R.R. Ali, None; A.T. Moore, None.
  • Footnotes
    Support  Medical Research Council (MRC) UK ; European Union AAV-EYE ; Fonds National Suisse de la Recherche Scientifique ; SICPA Foundation
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 3087. doi:https://doi.org/
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      M. H. Tan, H. V. Tran, A. J. Smith, R. Henderson, I. Russell-Eggitt, A. G. Robson, A. R. Webster, G. E. Holder, R. R. Ali, A. T. Moore; Clinical Spectrum of Patients With AIPL1 Mutations in Recessive Inherited Retinal Dystrophies. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3087. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To report the spectrum of clinical phenotype and genotype associated with Lebers Congenial Amaurosis (LCA) and autosomal recessive childhood onset retinal dystrophy caused by AIPL1 sequence variants in a single institution.

Methods: : A total of 292 unrelated probands with LCA or childhood onset autosomal recessive retinal dystrophy were screened for mutations in AIPL1 using a combination of microarray LCA chip analysis (Asper-Ophthalmics) and bidirectional sequencing of 6 exons including splice donor and acceptor sites. The results of clinical evaluation, electrophysiology (ERG) and imaging were reviewed.

Results: : Seven homozygotes and 12 compound heterozygotes were identified. Of the compound heterozygotes, 8 patients had novel sequence variants. The age of patients at time of onset of symptoms ranged from birth to 48 months (mean age of onset=9.8+/-3.5 months [SEM]). Visual acuities ranged from no light perception to logMar 0.12.Thirteen patients (68%) presented with nystagmus. Nyctalopia was present in 10 (53%). Fundus appearance ranged from near-normal appearance to variable degrees of chorioretinal atrophy and peripheral bone-spicule pigmentation. White dots at the level of the retinal pigment epithelium were seen in 9 (42%) patients. Macular atrophy was present in 10 (53%), mostly in patients with homozygous or null mutations. OCT analysis showed variable retinal thinning. Goldman perimetry showed severe constriction. In 5 patients tested according to International Standards, rod ERG was undetectable in 7 of 10 eyes and markedly subnormal in 3 eyes of 2 subjects. Bright flash ERG a-waves were undetectable in 5 of 10 eyes and subnormal in the others. In the 3 subjects with detectable 30Hz flicker ERGs, waveforms were markedly delayed and reduced. In 4 individuals tested with surface peri-orbital electrodes, ERGs were undetectable or subnormal consistent with generalized cone and rod system dysfunction.

Conclusions: : Mutations in the AIPL1 gene result in a spectrum of phenotypes. Null mutations are more likely to be associated with severe retinal disease and maculopathy.

Keywords: gene screening • mutations • retinal degenerations: hereditary 
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