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

Masahiko Satoda, Feng Zhao, George A. Diaz, John Burn, Judith Goodship, H. Rosemarie Davidson, Mary Ella M. Pierpont, Bruce D. Gelb

Research output: Contribution to journalArticlepeer-review

236 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)42-46
Number of pages5
JournalNature Genetics
Issue number1
StatePublished - May 2000
Externally publishedYes

Bibliographical note

Funding Information:
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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