Predictors of visual acuity and genotype-phenotype correlates in a cohort of patients with Stargardt disease.
OBJECTIVE
To assess the genotypic diversity in patients with Stargardt disease and to characterise epidemiological and genotypic predictors of phenotype.


METHODS
Retrospective, cross-sectional study of 112 patients with Stargardt disease. We evaluated the correlation between age at presentation, best-corrected visual acuity (BCVA), and ABCA4 genotypes.


RESULTS
Mean age at presentation was 30 ± 16 years (range 6-78 years) for the 112 patients of 104 families. 98 of 90 families had a probable molecular diagnosis. We found that BCVA is not related to age of presentation in a linear or polynomial manner; that BCVA of patients presenting in the first decade was significantly worse than those presenting in later decades (p=0.04); that patients who harboured two or more mutations presented earlier and had worse BCVA than those with no or 1 mutation identified by any method of testing (n=112, p=3.29 × 10(-6)) or by full sequencing (n=32, p=0.02); that 16 patients with c.5882G>A allele demonstrated better BCVA than the remaining patients (p=0.01); and that 10 patients with the c.5461-10T>C mutation presented earlier (p=0.02 × 10(-5)) and had more severe disease.


CONCLUSIONS
Epidemiological and genotypical findings portend visual prognosis in patients with Stargardt disease. Select sequence variations in ABCA4 may confer a specific phenotype. The present data will help in assessing patients for emerging therapies.
Abrahamson Eye Institute, Cincinnati Children's Hospital Medical Center, , Cincinnati, Ohio, USA.
Virginia
V
Miraldi Utz
Razek Georges
RG
Coussa
Meghan J
MJ
Marino
Aimee V
AV
Chappelow
Gayle J
GJ
Pauer
Stephanie A
SA
Hagstrom
Elias I
EI
Traboulsi
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D003430:Cross-Sectional Studies; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012189:Retrospective Studies; D000080362:Stargardt Disease; D041623:Tomography, Optical Coherence; D014792:Visual Acuity / Q000502:physiology*; D055815:Young Adult
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters