McLeod syndrome, characterized by acanthocytosis and the absence of a 
red-blood-cell Kell antigen (Kx), is a multisystem disorder involving a 
late-onset myopathy, splenomegaly, and neurological defects. The locus for this 
syndrome has been mapped, by deletion analysis, to a region between the loci for 
Duchenne muscular dystrophy (DMD) and chronic granulomatous disease (CGD). In 
this study, we describe a new marker, 3BH/R 0.3 (DXS 709), isolated by cloning 
the deletion breakpoint of a DMD patient. A long-range restriction map of Xp21, 
encompassing the gene loci for McLeod and CGD, was constructed, and multiple CpG 
islands were found clustered in a 700-kb region. Using the new marker, we have 
limited the McLeod syndrome critical region to 150-380-kb. Within this interval, 
two CpG-rich islands which may represent candidate sites for the McLeod gene 
were identified.