PMID- 10398730
OWN - NLM
STAT- MEDLINE
DCOM- 19990714
LR  - 20211203
IS  - 1090-0535 (Electronic)
IS  - 1090-0535 (Linking)
VI  - 5
DP  - 1999 Jul 2
TI  - Four polymorphic variations in the PEDF gene identified during the mutation
      screening of patients with Leber congenital amaurosis.
PG  - 10
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.
FAU - Koenekoop, R
AU  - Koenekoop R
AD  - McGill Ocular Genetics Laboratory, Montreal Children's Hospital Research
      Institute, Montreal, Canada. rkoeoph@mch.mcgill.ca
FAU - Pina, A L
AU  - Pina AL
FAU - Loyer, M
AU  - Loyer M
FAU - Davidson, J
AU  - Davidson J
FAU - Robitaille, J
AU  - Robitaille J
FAU - Maumenee, I
AU  - Maumenee I
FAU - Tombran-Tink, J
AU  - Tombran-Tink J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 19990702
PL  - United States
TA  - Mol Vis
JT  - Molecular vision
JID - 9605351
RN  - 0 (Eye Proteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Proteins)
RN  - 0 (Serpins)
RN  - 0 (pigment epithelium-derived factor)
SB  - IM
MH  - Amino Acid Substitution
MH  - Chromosomes, Human, Pair 17
MH  - Ethnicity/genetics
MH  - Eye Proteins/genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - Mutation
MH  - *Nerve Growth Factors
MH  - Optic Atrophies, Hereditary/*genetics
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Genetic
MH  - Polymorphism, Single-Stranded Conformational
MH  - Proteins/*genetics
MH  - Serpins/*genetics
EDAT- 1999/07/10 00:00
MHDA- 1999/07/10 00:01
CRDT- 1999/07/10 00:00
PHST- 1999/07/10 00:00 [pubmed]
PHST- 1999/07/10 00:01 [medline]
PHST- 1999/07/10 00:00 [entrez]
PST - epublish
SO  - Mol Vis. 1999 Jul 2;5:10.