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Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis.
- Source :
-
Molecular vision [Mol Vis] 1999 Jul 02; Vol. 5, pp. 10. Date of Electronic Publication: 1999 Jul 02. - Publication Year :
- 1999
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Abstract
- Purpose: Leber congenital amaurosis (LCA) has been mapped to chromosome 17p13.1. From the candidate genes mapped to this region, thus far, only Retinal Guanylate Cyclase (RetGC), has been found to have pathogenic LCA mutations, in families from North African origin. However, early reports, demonstrated eight LCA families linked to 17p13.1, but only four of them showed mutations in RetGC. Mapped in proximity to this locus is the candidate gene Pigment Epithelium Derived actor (PEDF), a factor implicated in photoreceptor differentiation and neuronal survival. Our purpose in this study was to identify mutations and polymorphisms in the PEDF gene in LCA patients of diverse ethnic origin.<br />Methods: Automated genotyping with four 17p13.1 markers flanking the PEDF gene was performed to assess homozygosity and PCR-SSCP combined with direct sequencing was used to detect mutations in the PEDF gene in 17 LCA patients.<br />Results: Homozygosity of markers D17S796 and D17S804 was found and four new intragenic basepair alterations were discovered: a Met72Thr polymorphism in exon 3 (T331C), a Thr130Thr polymorphism in exon 4 (T506C), a G to A transition in intron 5 (nine base pairs upstream from splice acceptor site), and a Tyr321Tyr polymorphism in exon 7 (C1079T) were detected.<br />Conclusions: We report the discovery of four new polymorphic alterations in the PEDF gene in LCA patients and exclude by RFLP analysis the PEDF gene as a common cause of Leber congenital amaurosis. These single nucleotide polymorphisms will aid in future linkage analysis of complex multifactorial diseases involving retinal and RPE dysfunctions.
- Subjects :
- Amino Acid Substitution
Chromosomes, Human, Pair 17
Ethnicity genetics
Eye Proteins genetics
Female
Humans
Male
Mutation
Pedigree
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Single-Stranded Conformational
Nerve Growth Factors
Optic Atrophies, Hereditary genetics
Proteins genetics
Serpins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1090-0535
- Volume :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular vision
- Publication Type :
- Academic Journal
- Accession number :
- 10398730