Journal article
Transcription Factor SIX5 Is Mutated in Patients with Branchio-Oto-Renal Syndrome
American journal of human genetics, Vol.80(4), pp.800-804
04/2007
DOI: 10.1086/513322
PMID: 17357085
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.
Details
- Title: Subtitle
- Transcription Factor SIX5 Is Mutated in Patients with Branchio-Oto-Renal Syndrome
- Creators
- Bethan E Hoskins - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Carl H Cramer - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Derek Silvius - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Dan Zou - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Richard M Raymond - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Dana J Orten - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)William J Kimberling - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Richard J. H Smith - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Dominique Weil - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Christine Petit - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Edgar A Otto - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Pin-Xian Xu - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)Friedhelm Hildebrandt - Departments of Pediatrics and of Human Genetics, University of Michigan, Ann Arbor (B.E.H.; C.H.C.; R.M.R; E.A.O.; F.H.); McLaughlin Research Institute for Biomedical Sciences, Great Falls, MT (D.S.; D.Z.; P.-X.X.); The Usher Syndrome Center, Boys Town National Research Hospital, Omaha (D.J.O.; W.J.K.); Departments of Otolaryngology, Pediatrics, and Internal Medicine, University of Iowa, Iowa City (R.J.H.S.); Unité de Génétique des Déficits Sensoriels, INSERM UMRS587, Institut Pasteur, Paris (D.W.; C.P.); and Department of Human Genetics, Mount Sinai School of Medicine, New York (P.-X.X.)
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.80(4), pp.800-804
- DOI
- 10.1086/513322
- PMID
- 17357085
- NLM abbreviation
- Am J Hum Genet
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Publisher
- The American Society of Human Genetics
- Alternative title
- Mutations in SIX5 Cause BOR
- Language
- English
- Date published
- 04/2007
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Otolaryngology; Internal Medicine
- Record Identifier
- 9984007180702771
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