January 2013
Volume 54, Issue 1
Letters to the Editor  |   January 2013
Retinal Phenotypes in Patients Homozygous for the G1961E Mutation in the ABCA4 Gene
Author Notes
Investigative Ophthalmology & Visual Science January 2013, Vol.54, 520. doi:10.1167/iovs.12-11472
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      David S. M. Burton, Manir Ali, Martin McKibbin; Retinal Phenotypes in Patients Homozygous for the G1961E Mutation in the ABCA4 Gene. Invest. Ophthalmol. Vis. Sci. 2013;54(1):520. doi: 10.1167/iovs.12-11472.

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

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We read with great interest the article by Burke et al., “Retinal Phenotypes in Patients Homozygous for the G1961E Mutation in the ABCA4 Gene.” 1  
The article, which describes a series of 12 patients and the range of ocular phenotypes associated with homozygosity for the G1961E mutation in the ABCA4 gene, concludes that the phenotype is usually at the milder end of the disease spectrum and with a later onset of visual symptoms than would be typically seen in Stargardt disease. 
We have recently seen two Asian male siblings with visual loss beginning late in the third decade. The asymptomatic parents were first cousins and four of the seven children were affected. In addition to loss of visual acuity, the proband reported increasing light sensitivity and used tinted lenses both indoors and outside. Visual acuity at the time of examination, aged 32 years, was counting fingers and hand movements only. There was a bull's eye maculopathy and flecks, limited to the perifoveal area. Although the appearance was in keeping with Stargardt disease, the late age of onset and the limited area of retinal involvement were felt to be unusual. However, genetic analysis subsequently identified heterozygous mutations in the ABCA4 gene, that is, G1961E and a novel splice site mutation (c.3328+1G>C). 
An earlier study by Cella et al. 2 reported the phenotype of patients who were both heterozygous and homozygous for the G1961E mutation. Three of the 15 cases were homozygous but the latest age of onset of 67 years was in a patient with heterozygous ABCA4 mutations. The phenotype for the heterozygous cases is similar to that reported by Simonelli and colleagues. 3 Collectively, these reports suggest that there may not be a meaningful difference in the phenotype and specifically the age of onset between homozygous and heterozygous carriers of the G1961E mutation. 
Burke TR Fishman GA Zernant J Retinal phenotypes in patients homozygous for the G1961E mutation in the ABCA4 gene. Invest Ophthalmol Vis Sci . 2012; 53: 4458–4467. [CrossRef] [PubMed]
Cella W Greenstein VC Zernant-Rajang J G1961E mutant allele in the Stargardt disease gene ABCA4 causes bull's eye maculopathy. Exp Eye Res . 2009; 18: 16–24. [CrossRef]
Simonelli F Testa F Zernant J Genotype-phenotype correlation in Italian families with Stargardt disease. Ophthalmic Res . 2005; 37: 159–167. [CrossRef] [PubMed]

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