The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1–SIX1–DNA complexes
Open accessAbstract
Urinary tract malformations constitute the most frequent cause of chronic renal failure in the first two decades of life. Branchio-otic (BO) syndrome is an autosomal dominant developmental disorder characterized by hearing loss. In branchio-oto-renal (BOR) syndrome, malformations of the kidney or urinary tract are associated. Haploinsufficiency for the human gene EYA1 , a homologue of the Drosophila gene eyes absent ( eya ), causes BOR and BO syndromes. We recently mapped a locus for BOR/BO syndrome ( BOS3 ) to human chromosome 14q23.1. Within the 33-megabase critical genetic interval, we located the SIX1 , SIX4 , and SIX6 genes, which act within a genetic network of EYA and PAX genes to regulate organogenesis. These genes, therefore, represented excellent candidate genes for BOS3 . By direct sequencing of exons, we identified three different SIX1 mutations in four BOR/BO kindreds, thus identifying SIX1 as a gene causing BOR and BO syndromes. To elucidate how these mutations cause disease, we analyzed the functional role of these SIX1 mutations with respect to protein–protein and protein–DNA interactions. We demonstrate that all three mutations are crucial for Eya1–Six1 interaction, and the two mutations within the homeodomain region are essential for specific Six1–DNA binding. Identification of SIX1 mutations as causing BOR/BO offers insights into the molecular basis of otic and renal developmental diseases in humans.
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Cites
Molecular Cloning: A Laboratory Manual
Sambrook, J., Fritsch, E., & Maniatis, T. (1989) · UCLA - Biblioteca de Ciencias de la Salud · Cited by 133,589
Eya1-deficient mice lack ears and kidneys and show abnormal apoptosis of organ primordia
Xu, P.-X., Adams, J., Peters, H., Brown, M. C., Heaney, S., & Maas, R. (1999) · Nature Genetics · doi:10.1038/12722 · Cited by 727
Self-citationAbdelhak, S., Kalatzis, V., Heilig, R., Compain, S., Samson, D., Vincent, C., Weil, D., Cruaud, C., Sahly, I., Leibovici, M., et al. (1997) · Nature Genetics · doi:10.1038/ng0297-157 · Cited by 671
Self-citationMutation of BSND causes Bartter syndrome with sensorineural deafness and kidney failure
Birkenhäger, R., Otto, E., Schürmann, M. J., Vollmer, M., Ruf, E.-M., Maier-Lutz, I., Beekmann, F., Fekete, A., Omran, H., Feldmann, D., et al. (2001) · Nature Genetics · doi:10.1038/ng752 · Cited by 539
Self-citationSix1 is required for the early organogenesis of mammalian kidney
Xu, P.-X., Zheng, W., Huang, L., Maire, P., Laclef, C., & Silvius, D. (2003) · Development · doi:10.1242/dev.00536 · Cited by 361
Self-citationThe role of Six1 in mammalian auditory system development
Zheng, W., Huang, L., Wei, Z.-B., Silvius, D., Tang, B., & Xu, P.-X. (2003) · Development · doi:10.1242/dev.00628 · Cited by 333
Self-citationEya1 is required for the morphogenesis of mammalian thymus, parathyroid and thyroid
Xu, P.-X., Zheng, W., Laclef, C., Maire, P., Maas, R. L., Peters, H., & Xu, X. (2002) · Development · doi:10.1242/dev.129.13.3033 · Cited by 281
Self-citationAbdelhak, S. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.13.2247 · Cited by 240
Altered myogenesis in Six1-deficient mice
Laclef, C., Hamard, G., Demignon, J., Souil, E., Houbron, C., & Maire, P. (2003) · Development · doi:10.1242/dev.00440 · Cited by 236
Spitz, F., Demignon, J., Porteu, A., Kahn, A., Concordet, J.-P., Daegelen, D., & Maire, P. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14220 · Cited by 218
Cited by
The Cellular Basis of Kidney Development
Dressler, G. R. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.22.010305.104340 · Cited by 620
Genetic, environmental, and epigenetic factors involved in CAKUT
Nicolaou, N., Renkema, K. Y., Bongers, E. M. H. F., Giles, R. H., & Knoers, N. V. A. M. (2015) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.140 · Cited by 344
Exploring the genetic basis of early-onset chronic kidney disease
Vivante, A., & Hildebrandt, F. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2015.205 · Cited by 344
Self-citationThe genetic changes of Wilms tumour
Treger, T. D., Chowdhury, T., Pritchard-Jones, K., & Behjati, S. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0112-0 · Cited by 257
Kumar, J. P. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8335-4 · Cited by 252
Metadata
- Authors
- Ruf, R. G., Xu, P.-X., Silvius, D., Otto, E. A., Beekmann, F., Muerb, U. T., Kumar, S., Neuhaus, T. J., Kemper, M. J., Raymond, R. M., Brophy, P. D., Berkman, J., Gattas, M., Hyland, V., Ruf, E.-M., Schwartz, C., Chang, E. H., Smith, R. J. H., Stratakis, C. A., Weil, D., Petit, C., & Hildebrandt, F.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2004-05-12
- Volume
- 101
- Issue
- 21
- Pages
- 8090-8095
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2134371698
- Cited by
- 428
- References
- 15
- FWCI
- 9.16
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1–SIX1–DNA complexes. https://app.cochat.ai/papers/10.1073/pnas.0308475101
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- Ruf, R. G., Xu, P.-X., Silvius, D., Otto, E. A., Beekmann, F., Muerb, U. T., Kumar, S., Neuhaus, T. J., Kemper, M. J., Raymond, R. M., Brophy, P. D., Berkman, J., Gattas, M., Hyland, V., Ruf, E.-M., Schwartz, C., Chang, E. H., Smith, R. J. H., Stratakis, C. A., . . . Hildebrandt, F. (2004). SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1–SIX1–DNA complexes. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0308475101
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
