ClinVar

Freson et al. (2002) described a 2-generation family with X-linked thrombocytopenia and anemia (300367) in which affected individuals had a 652G-T transversion in the GATA1 gene, resulting in an asp218-to-tyr (D218Y) substitution. Zinc finger interaction studies revealed a stronger loss of affinity of D218Y-GATA1 than of D218G-GATA1 (305371.0002) for the essential transcription factor FOG1 (601950) and a disturbed GATA1 self-association. Comparison of the phenotypic characteristics of patients from both families revealed that platelet and erythrocyte morphology as well as expression levels of the platelet GATA1-target gene products were more profoundly disturbed for the hemizygote D218Y mutation. The D218Y allele (as opposed to the D218G allele) was not expressed in the platelets of a female carrier, while her leukocytes showed a skewed X-inactivation pattern. The authors concluded that the nature of the amino acid substitution at position 218 of the N-terminal zinc finger of GATA1 may be of crucial importance in determining the severity of the phenotype in X-linked macrothrombocytopenia patients and possibly also in inducing skewed X inactivation.