Cosegregation analysis of mutant ABCA4 allleles in families with both Stargardt disease (STGD) and age–related macular degeneration (AMD).

Abstract

Abstract: : Purpose: To evaluate whether AMD–affected relatives of Stargardt patients are more likely to be carriers of mutant STGD alleles than predicted based only on their position in the pedigree. Methods: Sixteen unrelated families segregating both Stargardt disease and AMD were considered. In one STGD patient of each family, the ABCA4 gene was screened for the most frequent mutations in France. A segregation analysis was subsequently performed for each mutant allele in AMD–affected relatives. The observed proportion of AMD–affected relatives ABCA4 mutation carriers was compared to the expected proportion based on chance alone. Results: So far, at least one of the most frequent ABCA4 mutations in France was found in 8/16 families. Of the ten AMD–affected relatives belonging to these eight families, 9/10 were found to be carriers of the disease allele, therefore P_observed = 0.90 while based on the genealogy only, the P_theoretical was equal to 0.431. These proportions were compared using the Chi square test. The difference between P_observed and P_theoretical is statistically significant (Χ² = 9.02, p<0.01). Conclusions: The first results of this study indicate that ABCA4 mutation carriers are predisposed to develop AMD more frequently than the general population. The whole ABCA4 coding sequence screening is ongoing in all families using both DHPLC and direct sequencing.

Keywords: retinal degenerations: hereditary • age–related macular degeneration • genetics