We identified a family with gray platelet syndrome (GPS) segregating as a 
sex-linked trait. Affected males had a mild bleeding disorder, thrombocytopenia, 
and large agranular platelets characteristic of GPS, while obligate carrier 
females were asymptomatic but had dimorphic platelets on peripheral smear. 
Associated findings included mild erythrocyte abnormalities in affected males. 
Linkage analysis revealed a 63 cM region on the X chromosome between markers 
G10578 and DXS6797, which segregated with the platelet phenotype and included 
the GATA1 gene. Sequencing of GATA1 revealed a G-to-A mutation at position 759 
corresponding to amino acid change Arg216Gln. This mutation was previously 
described as a cause of X-linked thrombocytopenia with thalassemia (XLTT) but 
not of gray platelet syndrome. Our findings suggest that XLTT is within a 
spectrum of disorders constituting the gray platelet syndrome, and we propose 
that GATA1 is an upstream regulator of the genes required for platelet 
alpha-granule biogenesis.