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L.M. Downey, H.M. Bottomley, S. Scott, J.E. Craig, D.A. Mackey, B. Appukuttan, J.T. Stout, C.F. Inglehearn, C. Toomes; Mutation Screening of FZD4 in Familial Exudative Vitreoretinopathy Patients . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3569.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: FZD4 was recently identified as the gene which when mutated causing familial exudative vitreoretinopathy (FEVR). It is found at the EVR1 locus on chromosome 11q. The purpose of this study was to screen this gene in a panel of FEVR patients to identify mutations. Methods: PCR products were generated from genomic DNA with primers designed to amplify the coding sequence of the gene and flanking intronic sequence. The PCR products were screened for mutations by single strand conformational polymorphism-heteroduplex analysis (SSCP-HA) and by direct sequencing. Results: This work is still ongoing but to date a number of different polymorphisms and mutations have been identified. A 2-bp deletion, 1501del(CT), was identified in a large American family creating a frameshift from codon 501 and premature stop at codon 533. A novel 1-bp deletion, 956del(G), was identified in an Australian patient resulting in a frameshift causing the substitution of 4 amino acids and a premature termination at codon 323. A novel nonsense mutation 1513C>T (Gln505Stop) was identified in an Australian family. None of these mutations were present in 100 control individuals. Conclusions: We have screened a panel of FEVR patients for mutations in the FZD4 gene. To date we have identified three mutations, two of which are novel. All the mutations identified so far result in the truncation of the 537 amino acid FZD4 protein. Although this work is still ongoing our initial results suggest that we have found far fewer mutations than expected. The majority of FEVR families reported in the literature link to the EVR1 locus but we have not found mutations in the majority of our patients. To rule out the possibility that we have missed mutations due to the limited sensitivity of SSCP-HA we are currently sequencing this gene in patients.
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