Frequency of variant erythrocytes at the glycophorin-A locus in two Bloom's syndrome patients.

Blood type MN is determined by a glycoprotein termed glycophorin A (GPA) which exists on the surface of erythrocytes, and the difference between the M and N types is derived from the presence of 2 different amino acids in the amino-terminal portion (Furthmayer, 1978). Using a pair of fluorescence-labeled monoclonal antibodies specific to each GPA, somatic mutations in erythrocytes of MN heterozygotes at the GPA-M and -N alleles can be quantitatively determined using a flow sorter (Langlois et al., 1986). Our results for 2 Bloom's syndrome (BS) patients showed that variants either lost expression of one allele (simple gene inactivation or loss) or expressed only one allele at twice the normal level (most probably somatic recombination) occurring at a frequency of about 1-3 per 10(3) erythrocytes. The flow cytometric patterns of erythrocytes from the BS patients showed a typical smear of variants bearing intermediate levels of expression of one GPA allele, indicating that the real variant frequency is even greater than that measured. On the other hand, the parents heterozygous for the BS gene showed variant frequencies (1-8 x 10(-5)) within the normal range. These data strongly support the hypothesis that the cancer proneness of BS patients is due to their increased frequency of spontaneous mutations and somatic recombination.