PURPOSE. To investigate whether individuals, with no family history of ataxia telangiectasia (AT), in whom idiopathic or radiation-induced ocular telangiectasia developed are carriers of ATM gene mutations. METHODS. The ATM cDNA from lymphoblastoid cell lines established from 16 patients with idiopathic retinal or choroidal telangiectasia and 14 patients with radiation-induced telangiectasia after radiotherapy for age-related macular degeneration (AMD) was screened using the restriction endonuclease fingerprinting technique. The frequency of each detected variant was determined in the French population by either a mass spectrometry-based technique or variant-specific endonuclease digestion. RESULTS. Twenty-one ATM missense alterations, at 10 different sites, 8 of which would result in an amino acid substitution at a conserved position in the ATM protein were found. Four were novel changes, three of which were not detected in the 128 French control subjects screened. Eleven of 16 of the individuals with either idiopathic polypoidal choroidal vasculopathy or juxtafoveolar retinal telangiectasis and 6 of 14 individuals that had choroidal telangiectasis after radiotherapy for AMD carried ATM sequence variants. These latter six individuals had a significantly shorter delay time before the presentation of this vasculopathy compared with those individuals who had a wild-type ATM (11.8 ± 3.4 months vs. 17.5 ± 4.5 months, P = 0.024). They had also received a lower average dose of X-rays, although this difference did not reach statistical significance (18.7 ± 3.9 Gy vs. 23.7 ± 5.6 Gy, P = 0.09). CONCLUSIONS. ATM missense variants could confer an AT-like phenotype and influence the formation of retinal and choroidal vascular abnormalities.
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience