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Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus

Nature Geneticsvolume 25pages4246 (2000) | Download Citation



Char syndrome is an autosomal dominant trait characterized by patent ductus arteriosus, facial dysmorphism and hand anomalies. Using a positional candidacy strategy, we mapped TFAP2B, encoding a transcription factor expressed in neural crest cells, to the Char syndrome critical region and identified missense mutations altering conserved residues in two affected families. Mutant TFAP2B proteins dimerized properly in vitro, but showed abnormal binding to TFAP2 target sequence. Dimerization of both mutants with normal TFAP2B adversely affected transactivation, demonstrating a dominant-negative mechanism. Our work shows that TFAP2B has a role in ductal, facial and limb development and suggests that Char syndrome results from derangement of neural-crest-cell derivatives.

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We thank the two Char family members for their participation and J. Licht for critical reading of this manuscript. This study was supported in part by NIH grants to B.D.G. (HD01294 and HD38018).

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Author notes

  1. Masahiko Satoda and Feng Zhao: These authors contributed equally to this work.


  1. Departments of Pediatrics, Mount Sinai School of Medicine, New York, New York, USA

    • Masahiko Satoda
    • , Feng Zhao
    • , George A. Diaz
    •  & Bruce D. Gelb
  2. Departments of Human Genetics, Mount Sinai School of Medicine, New York, New York, USA

    • George A. Diaz
    •  & Bruce D. Gelb
  3. School of Biochemistry and Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, UK

    • John Burn
    •  & Judith Goodship
  4. Duncan Guthrie Institute of Medical Genetics, Yorkhill, Glasgow, UK

    • H. Rosemarie Davidson
  5. Department of Pediatrics, University of Minneapolis, Minnesota, USA

    • Mary Ella M. Pierpont


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Correspondence to Bruce D. Gelb.

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