Research Article

Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR†

  1. Dana J. Orten1,
  2. Stephanie M. Fischer2,
  3. Jessica L. Sorensen2,
  4. Uppala Radhakrishna1,
  5. Cor W.R.J. Cremers3,
  6. Henri A.M. Marres3,
  7. Guy Van Camp4,
  8. Katherine O. Welch5,
  9. Richard J.H. Smith2,
  10. William J. Kimberling1,*

Article first published online: 25 JAN 2008

DOI: 10.1002/humu.20691

Issue

Human Mutation

Human Mutation

Special Issue: Focus on Pharmacogenetics

Volume 29, Issue 4, pages 537–544, April 2008

Additional Information

How to Cite

Orten, D. J., Fischer, S. M., Sorensen, J. L., Radhakrishna, U., Cremers, C. W., Marres, H. A., Van Camp, G., Welch, K. O., Smith, R. J. and Kimberling, W. J. (2008), Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR. Human Mutation, 29: 537–544. doi: 10.1002/humu.20691

Author Information

  1. 1

    Department of Genetics, Boys Town National Research Hospital, Omaha, Nebraska

  2. 2

    Department of Otolaryngology, Head and Neck Surgery, University of Iowa, Iowa City, Iowa

  3. 3

    Department of Otorhinolaryngology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

  4. 4

    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium

  5. 5

    Department of Biology, Gallaudet University, Washington, DC

*Department of Genetics, Boys Town National Research Hospital, 555 North 30th Street, Omaha, NE 68164

  1. †

    Communicated by Maria Rita Passos-Bueno

Publication History

  1. Issue published online: 10 MAR 2008
  2. Article first published online: 25 JAN 2008
  3. Manuscript Accepted: 31 OCT 2007
  4. Manuscript Received: 31 JAN 2007

Funded by

  • National Institutes of Health (NIH)–National Institute of Dental and Craniofacial Research (NIDCR). Grant Number: 5R01DE014090-04
  • NIH–National Institute on Deafness and Other Communication Disorders (NIDCD). Grant Numbers: 5R01DC003544-09, 5R01DC04293

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Keywords:

  • branchio-oto-renal syndrome;
  • mutation analysis;
  • genetic heterogeneity;
  • EYA1

Abstract

Branchio-oto-renal syndrome (BOR) is an autosomal dominant disorder characterized by the association of branchial and external ear malformations, hearing loss, and renal anomalies. The phenotype varies from ear pits to profound hearing loss, branchial fistulae, and kidney agenesis. The most common gene mutated in BOR families is EYA1, a transcriptional activator. Over 80 different disease-causing mutations have been published (www.healthcare.uiowa.edu/labs/pendredandbor/, last accessed 20 November 2007). We analyzed the EYA1 coding region (16 exons) from 435 families (345 at the University of Iowa [UI] and 95 at Boys Town National Research Hospital [BTNRH], including five at both) and found 70 different EYA1 mutations in 89 families. Most of the mutations (56/70) were private. EYA1 mutations were found in 31% of families (76/248) fitting established clinical criteria for BOR and 7% of families with questionable BOR phenotype (13/187). Severity of the phenotype did not correlate with type of mutation nor with the domain involved. These results add considerably to the spectrum of EYA1 mutations associated with BOR and indicate that the BOR phenotype is an indication for molecular studies to diagnose EYA1-associated BOR. Hum Mutat 29(4), 537–544, 2008. © 2008 Wiley-Liss, Inc.

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