title: Mutation characterization in the GATA-1 gene in patients with Down's Syndrome diagnosed with transient abnormal myelopoiesis or acute megakaryoblastic leukemia.
abstract: Patients with Down's Syndrome have a higher risk of developing acute megakaryoblastic leukemia (AML). Ten per cent of newborn infants with this syndrome have transient abnormal myelopoiesis (TAM), indistinguishable from AML, which generally remits spontaneously. A high incidence of GATA-1 gene mutations was described in both groups of patients. Fourteen bone marrow DNA samples (10 ATM/4 AML) were analyzed by PCR and sequencing; these samples were obtained from 13 patients with Down's Syndrome to describe the rate and mutation characteristics of the GATA-1 gene in the studied population and its consequences at a protein level. Mutations were detected in 10 out of 10 TAM and in 3 out of 4 AML, which at a protein level would result in an early termination codon (n= 5), alterations in the splicing site (n= 6) or sequence change (n= 3). The high rate of GATA-1 gene mutations was confirmed in newborn infants with Down's Syndrome and MAT or AML.
authors.forename: Adrián P
authors.initials: AP
authors.lastname: Mansini
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Rubio
authors.forename: Jorge G
authors.initials: JG
authors.lastname: Rossi
authors.forename: Marta S
authors.initials: MS
authors.lastname: Gallego
authors.forename: Adriana
authors.initials: A
authors.lastname: Medina
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Zubizarreta
authors.forename: María S
authors.initials: MS
authors.lastname: Felice
authors.forename: Cristina N
authors.initials: CN
authors.lastname: Alonso
mesh_terms: D002675:Child, Preschool; D004314:Down Syndrome / Q000150:complications* / Q000235:genetics*; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007947:Leukemia, Megakaryoblastic, Acute / Q000150:complications* / Q000235:genetics*; D007955:Leukemoid Reaction / Q000150:complications* / Q000235:genetics*; D008297:Male; D009154:Mutation
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human