Spontaneous and induced chromosome breakage in chorionic villus samples: a cytogenetic approach to first trimester prenatal diagnosis of ataxia telangiectasia syndrome.

Patients with ataxia telangiectasia (AT) syndrome exhibit a high level of spontaneous chromosome aberrations, with hypersensitivity to gamma radiation and radiomimetic chemicals at the chromosomal and cellular level. Previously pregnancies at risk for AT have been screened solely by analysis of amniotic fluid samples. In this report we describe a cytogenetic approach to the prenatal diagnosis of AT using chorionic villus sampling (CVS). Levels of spontaneous and induced (gamma radiation and bleomycin) chromosome breakage were established in direct, semidirect, and culture preparations of CVS samples from normal pregnancies. The methods developed were then successfully applied to the screening of a pregnancy at risk for AT. Semidirect preparations showed normal levels of chromosome breakage, and this result was further confirmed in chorion, amniotic fluid, and lymphocyte cultures. In chorion villus samples, gamma radiation is probably the easiest and most reliable way of discriminating between unaffected fetuses and those with AT.