Genome-wide Enrichment of De Novo Coding Mutations in Orofacial Cleft Trios

Madison R. Bishop, Kimberly K. Diaz Perez, Miranda Sun, Samantha Ho, Pankaj Chopra, Nandita Mukhopadhyay, Jacqueline B. Hetmanski, Margaret A. Taub, Lina M. Moreno-Uribe, Luz Consuelo Valencia-Ramirez, Claudia P. Restrepo Muñeton, George Wehby, Jacqueline T. Hecht, Frederic Deleyiannis, Seth M. Weinberg, Yah Huei Wu-Chou, Philip K. Chen, Harrison Brand, Michael P. Epstein, Ingo RuczinskiJeffrey C. Murray, Terri H. Beaty, Eleanor Feingold, Robert J. Lipinski, David J. Cutler, Mary L. Marazita, Elizabeth J. Leslie

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)


Although de novo mutations (DNMs) are known to increase an individual's risk of congenital defects, DNMs have not been fully explored regarding orofacial clefts (OFCs), one of the most common human birth defects. Therefore, whole-genome sequencing of 756 child-parent trios of European, Colombian, and Taiwanese ancestry was performed to determine the contributions of coding DNMs to an individual's OFC risk. Overall, we identified a significant excess of loss-of-function DNMs in genes highly expressed in craniofacial tissues, as well as genes associated with known autosomal dominant OFC syndromes. This analysis also revealed roles for zinc-finger homeobox domain and SOX2-interacting genes in OFC etiology.

Original languageEnglish
Pages (from-to)124-136
Number of pages13
JournalAmerican Journal of Human Genetics
Issue number1
Publication statusPublished - Jul 2 2020


  • de novo mutations
  • orofacial clefts
  • trios
  • whole genome sequencing

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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