PMID- 10077612
OWN - NLM
STAT- MEDLINE
DCOM- 19990520
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 6
DP  - 1999 Mar 16
TI  - Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome
      mutations.
PG  - 2919-24
AB  - To better understand the role of TBX5, a T-box containing transcription factor in
      forelimb and heart development, we have studied the clinical features of
      Holt-Oram syndrome caused by 10 different TBX5 mutations. Defects predicted to
      create null alleles caused substantial abnormalities both in limb and heart. In
      contrast, missense mutations produced distinct phenotypes: Gly80Arg caused
      significant cardiac malformations but only minor skeletal abnormalities; and
      Arg237Gln and Arg237Trp caused extensive upper limb malformations but less
      significant cardiac abnormalities. Amino acids altered by missense mutations were
      located on the three-dimensional structure of a related T-box transcription
      factor, Xbra, bound to DNA. Residue 80 is highly conserved within T-box sequences
      that interact with the major groove of target DNA; residue 237 is located in the 
      T-box domain that selectively binds to the minor groove of DNA. These structural 
      data, taken together with the predominant cardiac or skeletal phenotype produced 
      by each missense mutation, suggest that organ-specific gene activation by TBX5 is
      predicated on biophysical interactions with different target DNA sequences.
FAU - Basson, C T
AU  - Basson CT
AD  - Cardiology Division, Department of Medicine and Department of Cell Biology and
      Anatomy, Weill Medical College of Cornell University, The New York Hospital, New 
      York, NY 10021, USA.
FAU - Huang, T
AU  - Huang T
FAU - Lin, R C
AU  - Lin RC
FAU - Bachinsky, D R
AU  - Bachinsky DR
FAU - Weremowicz, S
AU  - Weremowicz S
FAU - Vaglio, A
AU  - Vaglio A
FAU - Bruzzone, R
AU  - Bruzzone R
FAU - Quadrelli, R
AU  - Quadrelli R
FAU - Lerone, M
AU  - Lerone M
FAU - Romeo, G
AU  - Romeo G
FAU - Silengo, M
AU  - Silengo M
FAU - Pereira, A
AU  - Pereira A
FAU - Krieger, J
AU  - Krieger J
FAU - Mesquita, S F
AU  - Mesquita SF
FAU - Kamisago, M
AU  - Kamisago M
FAU - Morton, C C
AU  - Morton CC
FAU - Pierpont, M E
AU  - Pierpont ME
FAU - Muller, C W
AU  - Muller CW
FAU - Seidman, J G
AU  - Seidman JG
FAU - Seidman, C E
AU  - Seidman CE
LA  - eng
SI  - GENBANK/U89353
GR  - HL03468/HL/NHLBI NIH HHS/United States
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  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor 5)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Adult
MH  - Amino Acid Sequence
MH  - Heart Defects, Congenital/*genetics
MH  - Humans
MH  - Infant
MH  - Limb Deformities, Congenital/*genetics
MH  - Molecular Sequence Data
MH  - *Mutation
MH  - Sequence Analysis, DNA
MH  - Syndrome
MH  - *T-Box Domain Proteins
MH  - Transcription Factors/*genetics
PMC - PMC15870
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
AID - 10.1073/pnas.96.6.2919 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2919-24. doi: 10.1073/pnas.96.6.2919.