The translational start codon ATG/methionine is numbered as +1. One novel disease-associated mutation [c.839T>C (p.Met280Thr)] was found. References of previously reported polymorphisms are indicated.
Letters to the Editor
Stargardt Disease with Preserved Central Vision: identification of a putative novel mutation in ATP-binding cassette transporter gene
Article first published online: 16 FEB 2010
Copyright © 2011 Acta Ophthalmologica Scandinavica Foundation
Volume 89, Issue 3, pages e297–e298, May 2011
How to Cite
Fujinami, K., Akahori, M., Fukui, M., Tsunoda, K., Iwata, T. and Miyake, Y. (2011), Stargardt Disease with Preserved Central Vision: identification of a putative novel mutation in ATP-binding cassette transporter gene. Acta Ophthalmologica, 89: e297–e298. doi: 10.1111/j.1755-3768.2009.01848.x
- Issue published online: 16 FEB 2010
- Article first published online: 16 FEB 2010
Stargardt disease (STGD) has a juvenile to young–adult onset, a rapid decrease of central vision and a progressive bilateral atrophy of the sensory retina and retinal pigment epithelium (RPE) in the macula. Yellow-orange flecks are often detected around the macula, the midretina and or both (Rotenstreich et al. 2003). Mutations in the gene encoding the ATP-binding cassette transporter gene (ABCA4) are responsible for autosomal recessive STGD (Allikmets 1997; Webster et al. 2001). We examined a patient who had the characteristic signs of STGD but had good visual acuity.
A 66-year-old man complained of photophobia and a paracentral scotoma which was present since his teens and had not worsened. None of his family members had similar symptoms. His visual acuity was 20/15 OU, and ophthalmoscopy identified a dark brown, well-demarcated area at the fovea surrounded by RPE atrophy and flecks (Fig. 1A). Fluorescein angiography showed window defects at the flecks and a dark choroid (Fig. 1B). The optical coherence tomographic (OCT) images showed a well-preserved sensory retina and normal thickness RPE at the fovea (Fig. 1C, D). The foveal area was surrounded by atrophic sensory retina and RPE. Static perimetry showed ring-shaped paracentral relative scotoma which surrounded the normal area seeing area of 5° (Fig. 1E). Focal macular electroretinograms (FMERGs) also demonstrated a well-preserved retinal function at the fovea (Fig. 1F). Compared to age-matched controls, the FMERGs had normal responses elicited by a 5-degree stimulus spot and severely reduced responses elicited by 10-degree and 15-degree spots (Fig. 1F, G). Genetic analysis with direct DNA sequencing of amplified products revealed four reported polymorphisms (Allikmets 1997; Briggs et al. 2001; Webster et al. 2001; Fukui et al. 2002) and one novel mutation, Met280Thr, in exon 7 of the ABCA4 gene (Table 1).
|Exon||Nucleotide Change||Effect Changes||Het/Hom||References|
|10||c.1269C>T||p.His424His||Hom||Webster AR et al.|
|45||c.6249C>T||p.Ile2083Ile||Het||Allikmets R et al.|
|46||c.6285T>C||p.Asp2095Asp||Het||Briggs CE et al.|
|49||c.6764G>T||p.Ser2255Ile||Het||Allikmets R et al.|
Our patient had clinical findings that were pathognomonic of typical STGD, except that the clinical course was stationary and he had 20/15 vision because of well-preserved foveal function. The preserved foveal area was small and well demarcated. Visual acuity, fundus appearance, OCT images, static perimetry and FMERGs supported the well-preserved foveal function. We report our case because the patient had a unique phenotype with a novel putative mutation in the ABCA4 gene, not yet shown to segregate with the disease.
The well-demarcated dark brown foveal RPE appeared to be hyperpigmented although the thickness measured by OCT was 29 μm which was within normal limits. The findings in our case could indicate that the non-atrophic foveal RPE had an effect in preserving the foveal morphology and function.
The inheritance of STGD is autosomal recessive; however, our patient had four polymorphisms and one heterozygous gene mutation c.839T>C in exon 7 in the ABCA4 gene. A second mutation was not found, but it may well exist outside of the coding sequence of the ABCA4 gene. The new mutation in our patient was located outside the known functional domains of ATP-binding or transmembrane site (Lewis et al. 1999), which may explain the mild effect of the missense mutation. We should also consider a modifier gene effect in our patient.
Although the relationship between the new mutation of the ABCA4 gene and the well-preserved foveal structure is unresolved, the unique phenotype and genotype of our patient may give additional information on the mechanism of photoreceptor degeneration in eyes with STGD.
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