Prenatal and postnatal diagnosis and carrier detection of Fanconi anemia by a cytogenetic method

Fanconi anemia (FA) is characterized by pancytopenia, spontaneous chromosome instability, and a variety of congenital anomalies. Variable phenotype and age of onset of anemia make accurate diagnosis difficult in some patients. We report a cytogenetic method for rapid diagnosis of FA homozygous blood lymphocytes and amniotic fluid cells, and FA heterozygous blood lymphocytes. When treated with 0.1 micrograms/ml of diepoxybutane, affected lymphocytes responded with approximately a 175-fold increase in chromosome breakage compared with that exhibited by similarly treated lymphocytes from normal individuals or patients who manifest some clinical features of FA. The breakage in affected lymphocytes was characterized by multiple complex chromatoid exchanges. Amniotic fluid cells from four fetuses at risk for FA were studied. Three of these were diagnosed as affected and the fourth as normal on the basis of spontaneous and diepoxybutane-induced chromosome breakage. Lymphocytes from FA heterozygotes showed a fourfold increase in chromosome breakage characterized by chromatid exchange when compared with control lymphocytes. Prenatal and postnatal diagnosis of FA and detection of carriers can therefore be performed with ease by making use of the method described here.