title: X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation.
abstract: 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.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Boston, 320 Longwood Avenue, Boston, MA, USA.
authors.forename: Venée N
authors.initials: VN
authors.lastname: Tubman
authors.forename: Jason E
authors.initials: JE
authors.lastname: Levine
authors.forename: Dean R
authors.initials: DR
authors.lastname: Campagna
authors.forename: Rita
authors.initials: R
authors.lastname: Monahan-Earley
authors.forename: Ann M
authors.initials: AM
authors.lastname: Dvorak
authors.forename: Ellis J
authors.initials: EJ
authors.lastname: Neufeld
authors.forename: Mark D
authors.initials: MD
authors.lastname: Fleming
mesh_terms: D019943:Amino Acid Substitution; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004913:Erythrocytes, Abnormal / Q000378:metabolism / Q000473:pathology; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006470:Hemorrhage / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D019655:Quantitative Trait, Heritable; D013577:Syndrome; D013921:Thrombocytopenia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human