Spontaneously arising red cells with a McLeod-like phenotype in normal donors

Very few human genes can be used to identify spontaneous inactivating somatic mutations. We hypothesized that because the XK gene is X-linked, it would be easy to identify spontaneously arising red cells with a phenotype resembling the McLeod syndrome, which results from inherited XK mutations. Here, by flow cytometry, we detect such phenotypic variants at a median frequency of 9 × 10−6 in neonatal cord blood samples and 39 × 10−6 in healthy adults (p = 0.004). It may be possible to further investigate the relationship between aging, mutations, and cancer using this approach.