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Previous Volume 351:346-353 July 22, 2004 Number 4 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Perspective by Johnson, L. V. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Age-related macular degeneration (AMD) is the most common cause of irreversible vision loss in the developed world. The study of a rare 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 402 patients with AMD and 429 control subjects from the same clinic population. Patients were examined by means of indirect ophthalmoscopy, slit-lamp microscopy, and fundus photography to establish the presence and phenotypic pattern of AMD. DNA samples were screened for sequence variations in five members of the fibulin gene family.

Results Amino acid–altering sequence variations were found in all five fibulin genes, many of which were observed only in patients with AMD. Several of the altered residues have been conserved during evolution. 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<0.01). In addition, these seven patients all had small, circular drusen, which are commonly referred to as basal laminar or cuticular drusen.

Conclusions 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, and the evolutionary conservation of the affected residues suggests that several of these variations may also be involved in AMD.

Source Information

From the Center for Macular Degeneration (E.M.S., T.A.B., S.R.R., M.H.K., P.A.M., C.G.E., T.L.C., V.C.S.) and the Howard Hughes Medical Institute (E.M.S., V.C.S.), University of Iowa, Iowa City; and the Department of Ophthalmology, University of Southampton, Southampton, United Kingdom (A.J.L.).

Address reprint requests to Dr. Stone at the Center for Macular Degeneration, University of Iowa Carver College of Medicine, 200 Hawkins Dr., Iowa City, IA 52242, or at edwin-stone{at}uiowa.edu.

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