March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
The Clinical Effect of Homozygous ABCA4 Alleles in 14 Patients
Author Affiliations & Notes
  • Kaoru Fujinami
    Genetics, Genetics,
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Panagiotis I. Sergouniotis
    Genetics, Genetics,
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Donna S. Mackay
    Genetics, Genetics,
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Alice E. Davidson
    Genetics, Genetics,
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Anthony T. Moore
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Anthony G. Robson
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Graham E. Holder
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Michel Michaelides
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Andrew R. Webster
    Moorfields Eye Hospital, London, United Kingdom
    UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships  Kaoru Fujinami, None; Panagiotis I. Sergouniotis, None; Donna S. Mackay, None; Alice E. Davidson, None; Anthony T. Moore, None; Anthony G. Robson, None; Graham E. Holder, None; Michel Michaelides, None; Andrew R. Webster, None
  • Footnotes
    Support  NIHR Biomedical Research Centre for MEH and IOO; Foundation Fighting blindness US; Fight For Sight; MEH Special trustees; Macular Disease Society;Suzuken Foundation, Daiwa Anglo-Japannese Foundation
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 4567. doi:
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      Kaoru Fujinami, Panagiotis I. Sergouniotis, Donna S. Mackay, Alice E. Davidson, Anthony T. Moore, Anthony G. Robson, Graham E. Holder, Michel Michaelides, Andrew R. Webster; The Clinical Effect of Homozygous ABCA4 Alleles in 14 Patients. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4567.

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

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Abstract
 
Purpose:
 

To report the phenotypic findings in a group of patients with homozygous ABCA4 alleles. Retinopathy due to mutation of ABCA4 is highly variable. The common occurrence of heterozygous variants hinders the determination of the severity of specific mutations. Thus a cohort of individuals with homozygous variants was ascertained to gain insight into the retinopathy caused by specific alleles.

 
Methods:
 

A detailed history was obtained. Colour, autofluorescence and SD-OCT imaging was investigated. ISCEV standard electrophysiology was undertaken for functional assessment. An ophthalmoscopic phenotype was assigned based on that reported by Fishman et al. Arch Ophthalmol. 1999. An electrophysiological phenotype was assigned based on the three groups reported by Lois et al. Arch Ophthalmol. 2001. ABCA4 mutation detection was performed with ABCR400 microarray (Asper biotech) and direct sequencing in relatives to assess segregation.

 
Results:
 

Overall 14/248 individuals (9/202 families) were identified to harbor presumed disease-associated homozygous ABCA4 variants including; p.R1300X, p.Q2220X, IVS28+4 C>T, p.V931M / p.R1705Q, p.R212C, p.C1488R, p.R1640W, p.G1961E. The summarized results of the clinical features are shown in the table. Five out of six patients, homozygous for presumed null alleles had early onset (<10yrs) disease and all six had group 3 electrophysiological phenotypes. Two siblings with p.G1961E had adult-onset disease, the type 1 ophthalmoscopic phenotype and group 1 electrophysiological phenotype.

 
Conclusions:
 

The phenotypes represented in patients with homozygous variants give insights into individual alleles. Null alleles have severe functional effects, certain missense alleles are similar to nulls, and the common allele, p.G1961E, has a mild structural and functional effect on the adult retina.  

 
Keywords: electroretinography: clinical • genetics • retinal degenerations: hereditary 
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