A 5-bp deletion in ELOVL4 is associated with two related forms of autosomal dominant macular dystrophy

Stargardt-like macular dystrophy (STGD3, MIM 600110) and autosomal dominant macular dystrophy (adMD) are inherited forms of macular degeneration chara cterized by decreased visual acuity, macular atrophy and extensive fundus f lecks(1-3). Genetic mapping data suggest that mutations in a single gene ma y be responsible for both conditions, already known to bear clinical resemb lance(1-3). Here we limit the minimum genetic region for STGD3 and adMD to a 0.6-cM interval by recombination breakpoint mapping and identify a single 5-bp deletion within the protein-coding region of a new retinal photorecep tor-specific gene, ELOVL4, in all affected members of STGD3 and adMD famili es. Bioinformatic analysis of ELOVL4 revealed that it has homology to a gro up of yeast proteins that function in the biosynthesis of Very long chain f atty acids. Our results are therefore the first to implicate the biosynthes is of fatty acids in the pathogenesis of inherited macular degeneration.