BACKGROUND:Age-related macular degeneration(AM-D)is the most common cause of irreversible vision loss in the developed world.The study of a ra re mendelian form of macular degeneration implicated fibulin genes in the ...BACKGROUND:Age-related macular degeneration(AM-D)is the most common cause of irreversible vision loss in the developed world.The study of a ra re mendelian form of macular degeneration implicated fibulin genes in the pathogenesis of more common forms of this disease.We evaluated five fibulin genes in a large series of patients with AMD.METHODS:We studied 402patients with AMD and 429control subjects from the same clinic pop-ulation.Patients were examined by m eans of indirect ophthalmoscopy,slit-lamp microsc opy,and fundus pho-tography to establish the presence a nd phenotypic pattern of AMD.DNA samples were screened for sequence vari-ations in five members of the fibulin gene family.RE-SULTS:Amino acid-altering sequence variations were found in all five fibulin genes,many of which were ob-served only in patients with AMD.Sev eral of the altered residues have been conserved during evolution.Seven of the 402patients with AMD had amino ac idaltering se-quence variations in the fibulin 5ge ne,whereas none were observed among 429control subjects(P<0.01).In addition,these seven patients all h ad small,circular drusen,which are commonly referred to as basal laminar or cuticular drusen.CONCLUSIONS:Missense mutations in the fibulin 5gene were found in 1.7percent of patients with AMD.Many variationsin other fibulin genes were also found in these patients,and the evolutionary con-servation of the affected residues s uggests that several of these variations may also be involved in AMD.展开更多
文摘BACKGROUND:Age-related macular degeneration(AM-D)is the most common cause of irreversible vision loss in the developed world.The study of a ra re mendelian form of macular degeneration implicated fibulin genes in the pathogenesis of more common forms of this disease.We evaluated five fibulin genes in a large series of patients with AMD.METHODS:We studied 402patients with AMD and 429control subjects from the same clinic pop-ulation.Patients were examined by m eans of indirect ophthalmoscopy,slit-lamp microsc opy,and fundus pho-tography to establish the presence a nd phenotypic pattern of AMD.DNA samples were screened for sequence vari-ations in five members of the fibulin gene family.RE-SULTS:Amino acid-altering sequence variations were found in all five fibulin genes,many of which were ob-served only in patients with AMD.Sev eral of the altered residues have been conserved during evolution.Seven of the 402patients with AMD had amino ac idaltering se-quence variations in the fibulin 5ge ne,whereas none were observed among 429control subjects(P<0.01).In addition,these seven patients all h ad small,circular drusen,which are commonly referred to as basal laminar or cuticular drusen.CONCLUSIONS:Missense mutations in the fibulin 5gene were found in 1.7percent of patients with AMD.Many variationsin other fibulin genes were also found in these patients,and the evolutionary con-servation of the affected residues s uggests that several of these variations may also be involved in AMD.
