title: Distinct GATA1 Point Mutations in Monozygotic Twins With Down Syndrome and Transient Abnormal Myelopoiesis From a Triplet Pregnancy: A Case Report and Review of Literature.
abstract: OBJECTIVE
  Down syndrome (DS)-associated transient abnormal myelopoiesis (TAM) or acute megakaryoblastic leukemia (AMKL) in monozygotic twins is exceedingly rare and has not been well characterized.
  
  
  METHODS
  We describe a unique case of monozygotic twins with simultaneous TAM from a triplet pregnancy at 34 weeks' gestation. Previously reported cases of TAM and DS-AMKL in monozygotic twins have been reviewed to compare with our cases. The current concept of a sequential multistep process in leukemogenesis and disease evolution of TAM into DS-AMKL through the collaboration among trisomy 21, GATA1, and other gene mutations is also reviewed.
  
  
  RESULTS
  Distinct GATA1 mutations are identified in our neonate twins with TAM from a triplet pregnancy, whereas precisely identical GATA1 mutations have been detected in all three monozygotic DS twins reported in the literature.
  
  
  CONCLUSIONS
  Identical GATA1 mutations in cases of monozygotic twins are likely derived from twin-twin transmission. Distinct GATA1 mutations identified in our neonate twins with TAM provide unequivocal evidence of independent intra-utero GATA1 mutations, a completely different mechanism of development of TAM in monozygotic twins from previously reported cases. Interaction of trisomy 21 and GATA1 mutation produces TAM, but additional gene mutations are required for TAM to transform into DS-AMKL.
authors.affiliation: From the Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora.
authors.forename: Liqun
authors.initials: L
authors.lastname: Yin
authors.affiliation: From the Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora.|Department of Pathology,, Denver Health Medical Center, Denver, CO.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovell
authors.affiliation: From the Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora.|Department of Pathology, Children's Hospital Colorado, Anschutz Medical Campus, Aurora.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Wilson
authors.affiliation: Department of Pathology, Children's Hospital Colorado, Anschutz Medical Campus, Aurora.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wei
authors.affiliation: From the Department of Pathology, University of Colorado, Anschutz Medical Campus, Aurora xiayuan.liang@childrenscolorado.org.|Department of Pathology, Children's Hospital Colorado, Anschutz Medical Campus, Aurora.
authors.forename: Xiayuan
authors.initials: X
authors.lastname: Liang
mesh_terms: D004200:Diseases in Twins / Q000235:genetics* / Q000473:pathology; D004314:Down Syndrome / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D050982:GATA1 Transcription Factor / Q000235:genetics*; D006801:Humans; D007231:Infant, Newborn; D007955:Leukemoid Reaction / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008297:Male; D017354:Point Mutation; D011247:Pregnancy; D059286:Pregnancy, Triplet; D014430:Twins, Monozygotic
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human
keywords: Down syndrome; GATA1 mutation; Transient abnormal myelopoiesis; Transient myeloproliferative disorder