A MODEL FOR ATM HETEROZYGOTE IDENTIFICATION IN A LARGE POPULATION - 4FOUNDER-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 hete rozygotes are at an elevated risk of breast cancer. ATM mutations occu r worldwide over the entire ATM gene, making it difficult to identify heterozygotes in large populations. However, some founder-effect mutat ions are specific for certain populations. Here, Fee present four muta tions in Costa Rican A-T patients that accounted for 86-93% of 41 pati ents studied in two batches. We have developed assays for rapid detect ion of these four mutations which can be used diagnostically. They wil l also enable the Costa Rican population to be used as a model for ana lyzing the role of ATM heterozygosity in cancer development and other disorders. (C) 1998 Academic Press.