Pigment epithelium derived factor as a candidate gene for Leber's congenital amaurosis

J. K. Davidson, J. Tink, M. Loyer, E. Traboulsi, I. Maumenee, R. K. Koenekoop

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Purpose. Lebens congenital amaurosis (_CA) has recently been mapped to chromosome 17p13.1. Pigment Epithelium Derived Factor (PEDF) has been shown to induce neuronal differentiation and also maps to chromosome 17p13.1‡. We hypothesize that LCA is caused by a defect in the PEDF gene which prevents proper differentiation and functioning of the developing retina. Methods. We obtained DNA from the blood of 18 families with LCA (5 multiplex and 13 simplex cases from around the world including China, Afghanistan, Greece, the United States and Canada). SSCP analysis, direct sequencing, and confirmation with restriction enzyme digestion was performed on these patients and 50 normal controls for all 8 exons of the PEDF gene. Results. We have found a Met-72-Ser mutation in exon 3 of the PEDF gene (creates a BssSI site) in 8 affected patients, but also in 13 of 25 normal controls. An intronic G to A transition (which destroys a BstUI site) 9 base pairs downstream from exon 5 was discovered in 4 affected patients. We also found 2 silent polymorphisms. One is a Thr-130-Thr transition within exon 4 (creates a BstEII site), and the other is a Tyr-321-Tyr transition in exon 7 (creates a MaeIII site). Conclusions. We are continuing our search for pathological mutations in the PEDF gene which may cause LCA by screening the entire PEDF promoter region. We are also analyzing the mRNA in patients with the intronic mutation to determine whether it causes erroneous splicing. Our current results will nonetheless simplify future linkage analyses involving the PEDF gene.

Original languageEnglish (US)
Pages (from-to)S991
JournalInvestigative Ophthalmology and Visual Science
Issue number3
StatePublished - Feb 15 1996

All Science Journal Classification (ASJC) codes

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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