A Model for ATM Heterozygote Identification in a Large Population: Four Founder-Effect ATM Mutations Identify Most of Costa Rican Patients with Ataxia Telangiectasia

Ataxia telangiectasia (A-T) is an autosomal recessive disorder with a broad range of clinical manifestations and a frequency of 1:40,000–100,000 live births. Epidemiological studies have suggested that A-T heterozygotes are at an elevated risk of breast cancer. ATM mutations occur worldwide over the entire ATM gene, making it difficult to identify heterozygotes in large populations. However, some founder-effect mutations are specific for certain populations. Here, we present four mutations in Costa Rican A-T patients that accounted for 86–93% of 41 patients studied in two batches. We have developed assays for rapid detection of these four mutations which can be used diagnostically. They will also enable the Costa Rican population to be used as a model for analyzing the role of ATM heterozygosity in cancer development and other disorders.