PMID- 10508512
OWN - NLM
STAT- MEDLINE
DCOM- 19991019
LR  - 20220331
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 23
IP  - 2
DP  - 1999 Oct
TI  - Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to
      develop acute myelogenous leukaemia.
PG  - 166-75
AB  - Familial platelet disorder with predisposition to acute myelogenous leukaemia
      (FPD/AML, MIM 601399) is an autosomal dominant disorder characterized by
      qualitative and quantitative platelet defects, and propensity to develop acute
      myelogenous leukaemia (AML). Informative recombination events in 6 FPD/AML
      pedigrees with evidence of linkage to markers on chromosome 21q identified an
      880-kb interval containing the disease gene. Mutational analysis of regional
      candidate genes showed nonsense mutations or intragenic deletion of one allele of
      the haematopoietic transcription factor CBFA2 (formerly AML1) that co-segregated 
      with the disease in four FPD/AML pedigrees. We identified heterozygous CBFA2
      missense mutations that co-segregated with the disease in the remaining two
      FPD/AML pedigrees at phylogenetically conserved amino acids R166 and R201,
      respectively. Analysis of bone marrow or peripheral blood cells from affected
      FPD/AML individuals showed a decrement in megakaryocyte colony formation,
      demonstrating that CBFA2 dosage affects megakaryopoiesis. Our findings support a 
      model for FPD/AML in which haploinsufficiency of CBFA2 causes an autosomal
      dominant congenital platelet defect and predisposes to the acquisition of
      additional mutations that cause leukaemia.
FAU - Song, W J
AU  - Song WJ
AD  - Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
FAU - Sullivan, M G
AU  - Sullivan MG
FAU - Legare, R D
AU  - Legare RD
FAU - Hutchings, S
AU  - Hutchings S
FAU - Tan, X
AU  - Tan X
FAU - Kufrin, D
AU  - Kufrin D
FAU - Ratajczak, J
AU  - Ratajczak J
FAU - Resende, I C
AU  - Resende IC
FAU - Haworth, C
AU  - Haworth C
FAU - Hock, R
AU  - Hock R
FAU - Loh, M
AU  - Loh M
FAU - Felix, C
AU  - Felix C
FAU - Roy, D C
AU  - Roy DC
FAU - Busque, L
AU  - Busque L
FAU - Kurnit, D
AU  - Kurnit D
FAU - Willman, C
AU  - Willman C
FAU - Gewirtz, A M
AU  - Gewirtz AM
FAU - Speck, N A
AU  - Speck NA
FAU - Bushweller, J H
AU  - Bushweller JH
FAU - Li, F P
AU  - Li FP
FAU - Gardiner, K
AU  - Gardiner K
FAU - Poncz, M
AU  - Poncz M
FAU - Maris, J M
AU  - Maris JM
FAU - Gilliland, D G
AU  - Gilliland DG
LA  - eng
SI  - GENBANK/AJ229041
SI  - GENBANK/AJ229042
SI  - GENBANK/AJ229043
SI  - GENBANK/AP000032
SI  - GENBANK/AP000033
SI  - GENBANK/AP000034
SI  - GENBANK/AP000035
SI  - GENBANK/AP000036
SI  - GENBANK/AP000037
SI  - GENBANK/AP000038
SI  - GENBANK/AP000039
SI  - GENBANK/AP000040
SI  - GENBANK/AP000041
SI  - GENBANK/AP000042
SI  - GENBANK/AP000043
SI  - GENBANK/AP000044
SI  - GENBANK/AP000045
SI  - GENBANK/AP000046
SI  - GENBANK/AP000047
SI  - GENBANK/AP000048
SI  - GENBANK/AP000049
SI  - GENBANK/AP000050
SI  - GENBANK/AP000051
SI  - GENBANK/AP000052
SI  - GENBANK/AP000053
SI  - GENBANK/AP000054
SI  - GENBANK/AP000055
SI  - GENBANK/AP000056
SI  - GENBANK/AP000057
GR  - R01 CA78545/CA/NCI NIH HHS/United States
GR  - R01 CA81932/CA/NCI NIH HHS/United States
GR  - R29 AI39536/AI/NIAID NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (Transcription Factors)
RN  - 63231-63-0 (RNA)
SB  - IM
CIN - Nat Genet. 1999 Oct;23(2):134-5. PMID: 10508502
MH  - Amino Acid Sequence
MH  - Base Sequence
MH  - Blood Platelets/metabolism
MH  - Chromosome Mapping
MH  - Colony-Forming Units Assay
MH  - Core Binding Factor Alpha 2 Subunit
MH  - DNA Mutational Analysis
MH  - *DNA-Binding Proteins
MH  - Family Health
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Hematopoiesis/genetics
MH  - Heterozygote
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Leukemia, Myeloid, Acute/*genetics
MH  - Male
MH  - Megakaryocytes/cytology/metabolism
MH  - Microsatellite Repeats
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Pedigree
MH  - *Proto-Oncogene Proteins
MH  - RNA/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sequence Deletion
MH  - Sequence Homology, Amino Acid
MH  - Sequence Homology, Nucleic Acid
MH  - Thrombocytopenia/*genetics
MH  - Transcription Factors/*genetics
EDAT- 1999/10/03 09:00
MHDA- 2001/03/23 10:01
CRDT- 1999/10/03 09:00
PHST- 1999/10/03 09:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/10/03 09:00 [entrez]
AID - 10.1038/13793 [doi]
PST - ppublish
SO  - Nat Genet. 1999 Oct;23(2):166-75. doi: 10.1038/13793.