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M Mauget-Faysse, J Hall, M Vuillaume, N Moullan, S Angèle, M Quaranta, M Friesen; Radiation-induced and Idiopathic Ocular Vasculopathies: Involvement of the ATM Gene . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2830.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The disease Ataxia Telangiectasia is extremely rare, however 1% of the general population has been estimated to be ATM heterozygotes. It has been predicted that carriers of a missense allele have an increased risk of developing clinical phenotypes associated with AT, such as radiation sensitivity, telangiectasias or cancer. This pilot study aimed to investigate whether 30 patients, with no family history of AT, who developed ocular telangiectasias, were carriers of ATM mutations Methods: 22 patients with either idiopathic polypoidal choroidal vasculopathy (IPCV), or radiation-induced choroidal telangiectasias (RICT) following radiotherapy for aged-related macular degeneration and 8 patients with idiopathic juxta-foveolar retinal telangiectasias (IJFRT) were investigated. A lymphoblastoid cell line (TEL line) was established and the cell line RNA was used to screen the ATM open reading frame for sequence alterations using the restriction endonuclease fingerprinting (REF) cDNA approach. All fragments with an altered REF pattern were sequenced to determine the exact modifications. The frequency of each change was then assessed in a French control population Results: A total of 21 ATM sequence variants were found in 17/30 patients. All were missense alterations, 8/10 of which would be predicted to result in an amino acid substitution in the ATM protein. Five were novel changes, but one has been detected in three French patients diagnosed with AT or an AT-like disorder. Although the numbers of individuals examined were small, the vast majority (7/8) of patients with IPCV and 50% with IJFRT had ATM sequence alterations. 6/14 patients who developed RICT had ATM sequence variants Conclusion: This result would support the hypothesis that missense ATM variants could confer an AT-like phenotype acting in a dominant negative fashion by enhancing radiation sensitivity and the formation of retinal and choroidal vascular abnormalities
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