Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome

Bethan E. Hoskins, Carl H. Cramer, Derek Silvius, Dan Zou, Richard M. Raymond, Dana J. Orten, William J Kimberling, Richard J.H. Smith, Dominique Weil, Christine Petit, Edgar A. Otto, Pin Xian Xu, Friedhelm Hildebrandt

Research output: Contribution to journalArticle

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Abstract

Branchio-oto-renal syndrome (BOR) is an autosomal dominant developmental disorder characterized by the association of branchial arch defects, hearing loss, and renal anomalies. Mutations in EYA1 are known to cause BOR. More recently, mutations in SIX1, which interacts with EYA1, were identified as an additional cause of BOR. A second member of the SIX family of proteins, unc-39 (SIX5), has also been reported to directly interact with eya-1 in Caenorhabditis elegans. We hypothesized that this interaction would be conserved in humans and that interactors of EYA1 represent good candidate genes for BOR. We therefore screened a cohort of 95 patients with BOR for mutations in SIX5. Four different heterozygous missense mutations were identified in five individuals. Functional analyses of these mutations demonstrated that two mutations affect EYA1-SIX5 binding and the ability of SIX5 or the EYA1-SIX5 complex to activate gene transcription. We thereby identified heterozygous mutations in SIX5 as a novel cause of BOR.

Original languageEnglish (US)
Pages (from-to)800-804
Number of pages5
JournalAmerican Journal of Human Genetics
Volume80
Issue number4
DOIs
StatePublished - Jan 1 2007

Fingerprint

Branchio-Oto-Renal Syndrome
Transcription Factors
Mutation
Branchial Region
Aptitude
Caenorhabditis elegans
Missense Mutation
Hearing Loss
Genes
Kidney

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Hoskins, B. E., Cramer, C. H., Silvius, D., Zou, D., Raymond, R. M., Orten, D. J., ... Hildebrandt, F. (2007). Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. American Journal of Human Genetics, 80(4), 800-804. https://doi.org/10.1086/513322

Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. / Hoskins, Bethan E.; Cramer, Carl H.; Silvius, Derek; Zou, Dan; Raymond, Richard M.; Orten, Dana J.; Kimberling, William J; Smith, Richard J.H.; Weil, Dominique; Petit, Christine; Otto, Edgar A.; Xu, Pin Xian; Hildebrandt, Friedhelm.

In: American Journal of Human Genetics, Vol. 80, No. 4, 01.01.2007, p. 800-804.

Research output: Contribution to journalArticle

Hoskins, BE, Cramer, CH, Silvius, D, Zou, D, Raymond, RM, Orten, DJ, Kimberling, WJ, Smith, RJH, Weil, D, Petit, C, Otto, EA, Xu, PX & Hildebrandt, F 2007, 'Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome', American Journal of Human Genetics, vol. 80, no. 4, pp. 800-804. https://doi.org/10.1086/513322
Hoskins BE, Cramer CH, Silvius D, Zou D, Raymond RM, Orten DJ et al. Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. American Journal of Human Genetics. 2007 Jan 1;80(4):800-804. https://doi.org/10.1086/513322
Hoskins, Bethan E. ; Cramer, Carl H. ; Silvius, Derek ; Zou, Dan ; Raymond, Richard M. ; Orten, Dana J. ; Kimberling, William J ; Smith, Richard J.H. ; Weil, Dominique ; Petit, Christine ; Otto, Edgar A. ; Xu, Pin Xian ; Hildebrandt, Friedhelm. / Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. In: American Journal of Human Genetics. 2007 ; Vol. 80, No. 4. pp. 800-804.
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