Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis.

R. Koenekoop, A. L. Pina, M. Loyer, J. Davidson, J. Robitaille, I. Maumenee, J. Tombran-Tink

Research output: Contribution to journalArticle

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. 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. 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. 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.

Original languageEnglish (US)
Number of pages1
JournalMolecular Vision
Volume5
StatePublished - Jul 2 1999

Fingerprint

Leber Congenital Amaurosis
Mutation
Genes
Exons
Guanylate Cyclase
Single-Stranded Conformational Polymorphism
Retinal Diseases
RNA Splice Sites
Base Pairing
Restriction Fragment Length Polymorphisms
Introns
Single Nucleotide Polymorphism
Epithelium
Chromosomes
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Ophthalmology

Cite this

Koenekoop, R. ; Pina, A. L. ; Loyer, M. ; Davidson, J. ; Robitaille, J. ; Maumenee, I. ; Tombran-Tink, J. / Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis. In: Molecular Vision. 1999 ; Vol. 5.
@article{fcf4d9515575419b933524c18c0f4582,
title = "Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis.",
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. 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. 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. 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.",
author = "R. Koenekoop and Pina, {A. L.} and M. Loyer and J. Davidson and J. Robitaille and I. Maumenee and J. Tombran-Tink",
year = "1999",
month = "7",
day = "2",
language = "English (US)",
volume = "5",
journal = "Molecular Vision",
issn = "1090-0535",

}

Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis. / Koenekoop, R.; Pina, A. L.; Loyer, M.; Davidson, J.; Robitaille, J.; Maumenee, I.; Tombran-Tink, J.

In: Molecular Vision, Vol. 5, 02.07.1999.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Four polymorphic variations in the PEDF gene identified during the mutation screening of patients with Leber congenital amaurosis.

AU - Koenekoop, R.

AU - Pina, A. L.

AU - Loyer, M.

AU - Davidson, J.

AU - Robitaille, J.

AU - Maumenee, I.

AU - Tombran-Tink, J.

PY - 1999/7/2

Y1 - 1999/7/2

N2 - 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. 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. 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. 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.

AB - 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. 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. 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. 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.

UR - http://www.scopus.com/inward/record.url?scp=17744415763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17744415763&partnerID=8YFLogxK

M3 - Article

C2 - 10398730

VL - 5

JO - Molecular Vision

JF - Molecular Vision

SN - 1090-0535

ER -