Purchase this article with an account.
Virginia M. Utz, Aimee V. Chappelow, Susan Crowe, Gayle J. Pauer, Stephanie A. Hagstrom, Elias I. Traboulsi; ABCA4 Genotypic Diversity And Phenotypic Correlates In Stargardt Disease. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4557.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
To characterize genotypic diversity and to correlate ABCA4 genotype with clinical phenotype in a population of patients with Stargardt disease.
We reviewed 244 patients with a clinical diagnosis of Stargardt Disease examined between 1998 and June 2011 at the Cole Eye Institute. The following data was extracted from the medical record: age, visual acuity, retinal abnormalities on initial and final visit, fluorescein angiographic changes, ERG amplitude/implicit time, optical coherence tomography and fundus autofluorescence whenever these studies were performed.
Sixty-seven distinct mutations were identified in 78 patients of 75 families, of which 22 were common to multiple patients. Five different mutations accounted for 50% of the identified disease alleles. In 35 of 78 patients (45%), only one mutant ABCA4 allele was detected, whereas in 13 patients (17 %) three disease-causing mutations were identified. The most common nucleotide change (c.5882G>A), a missense mutation resulting in a G1961E amino acid exchange, occurred in 11 alleles of 10 patients, and was associated with visual acuity better than 20/200 for all patients, ages 15 to 72 years. As reported previously, the presence of the c.5461-10T>C substitution, which is in linkage disequilibrium with a disease-causing mutation, was associated with early-onset disease, vision less than 20/200 and nystagmus by the second decade, as well as distinctive macular pigmentary clumping. Ten out of 11 unrelated African-American patients with known genotype shared 1 of 3 common mutations [c.6320G>A (R2107H), c.3602T>G (L1201R), c.3899G>A (R1300Q)] that in the present population were exclusive to the African-American subset.
Stargardt disease is less diverse phenotypically among patients with identical mutations than among Stargardt patients as a whole. ABCA4 mutation analysis may assist in estimating visual prognosis on an individual basis.
This PDF is available to Subscribers Only