A number of studies have suggested that both genetic and environmental factors play a role in age-related macular degeneration (AMD). In this study, the authors evaluated five fibulin genes in a large series of patients with AMD. The fibulins are a recently identified family of six extracellular matrix proteins that have roles in the assembly and stabilization of supramolecular extracellular-matrix-complexes. The authors studied 402 unrelated patients with AMD and 429 control subjects from the same clinic population. DNA samples were screened for sequence variations in five members of the fibulin gene family. Amino acid-altering sequence variations were found in all five fibulin genes, many of which were observed only in patients with AMD. Seven of the 402 patients with AMD had amino acid-altering sequence variations in the fibulin 5 gene, whereas none were observed among 429 control subjects (P < .01). Additionally, these seven patients all had small, circular drusen, which are commonly referred to as basal laminar or cuticular drusen. In this study, missense mutations in the fibulin 5 gene were found in 1.7 percent of patients with AMD. Many variations in other fibulin genes were also found in these patients. The authors conclude that the evolutionary conservation of the affected residues suggests that several of these variations may also be involved in AMD.—Valerie Biousse