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SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes.

Standard

SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. / Ruf, Rainer G; Xu, Pin-Xian; Silvius, Derek; Otto, Edgar A; Beekmann, Frank; Muerb, Ulla T; Kumar, Shrawan; Neuhaus, Thomas J; Kemper, Markus J.; Raymond, Richard M; Brophy, Patrick D; Berkman, Jennifer; Gattas, Michael; Hyland, Valentine; Ruf, Eva-Maria; Schwartz, Charles; Chang, Eugene H; Smith, Richard J H; Stratakis, Constantine A; Weil, Dominique; Petit, Christine; Hildebrandt, Friedhelm.

in: P NATL ACAD SCI USA, Jahrgang 101, Nr. 21, 21, 2004, S. 8090-8095.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Ruf, RG, Xu, P-X, Silvius, D, Otto, EA, Beekmann, F, Muerb, UT, Kumar, S, Neuhaus, TJ, Kemper, MJ, Raymond, RM, Brophy, PD, Berkman, J, Gattas, M, Hyland, V, Ruf, E-M, Schwartz, C, Chang, EH, Smith, RJH, Stratakis, CA, Weil, D, Petit, C & Hildebrandt, F 2004, 'SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes.', P NATL ACAD SCI USA, Jg. 101, Nr. 21, 21, S. 8090-8095. <http://www.ncbi.nlm.nih.gov/pubmed/15141091?dopt=Citation>

APA

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. P NATL ACAD SCI USA, 101(21), 8090-8095. [21]. http://www.ncbi.nlm.nih.gov/pubmed/15141091?dopt=Citation

Vancouver

Ruf RG, Xu P-X, Silvius D, Otto EA, Beekmann F, Muerb UT et al. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. P NATL ACAD SCI USA. 2004;101(21):8090-8095. 21.

Bibtex

@article{95f789eebc814e2599c747b78a676db9,
title = "SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes.",
abstract = "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.",
keywords = "Humans, Amino Acid Sequence, Molecular Sequence Data, Base Sequence, Gene Expression Regulation, Developmental, Protein Structure, Tertiary, Nuclear Proteins, Cell Line, Protein Binding, Macromolecular Substances, Genes, Reporter/genetics, Mutation/*genetics, Trans-Activators/*metabolism, Branchio-Oto-Renal Syndrome/*genetics, DNA/genetics/*metabolism, Homeodomain Proteins/chemistry/*genetics/*metabolism, Intracellular Signaling Peptides and Proteins, Protein Tyrosine Phosphatases, Humans, Amino Acid Sequence, Molecular Sequence Data, Base Sequence, Gene Expression Regulation, Developmental, Protein Structure, Tertiary, Nuclear Proteins, Cell Line, Protein Binding, Macromolecular Substances, Genes, Reporter/genetics, Mutation/*genetics, Trans-Activators/*metabolism, Branchio-Oto-Renal Syndrome/*genetics, DNA/genetics/*metabolism, Homeodomain Proteins/chemistry/*genetics/*metabolism, Intracellular Signaling Peptides and Proteins, Protein Tyrosine Phosphatases",
author = "Ruf, {Rainer G} and Pin-Xian Xu and Derek Silvius and Otto, {Edgar A} and Frank Beekmann and Muerb, {Ulla T} and Shrawan Kumar and Neuhaus, {Thomas J} and Kemper, {Markus J.} and Raymond, {Richard M} and Brophy, {Patrick D} and Jennifer Berkman and Michael Gattas and Valentine Hyland and Eva-Maria Ruf and Charles Schwartz and Chang, {Eugene H} and Smith, {Richard J H} and Stratakis, {Constantine A} and Dominique Weil and Christine Petit and Friedhelm Hildebrandt",
year = "2004",
language = "English",
volume = "101",
pages = "8090--8095",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "21",

}

RIS

TY - JOUR

T1 - SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes.

AU - Ruf, Rainer G

AU - Xu, Pin-Xian

AU - Silvius, Derek

AU - Otto, Edgar A

AU - Beekmann, Frank

AU - Muerb, Ulla T

AU - Kumar, Shrawan

AU - Neuhaus, Thomas J

AU - Kemper, Markus J.

AU - Raymond, Richard M

AU - Brophy, Patrick D

AU - Berkman, Jennifer

AU - Gattas, Michael

AU - Hyland, Valentine

AU - Ruf, Eva-Maria

AU - Schwartz, Charles

AU - Chang, Eugene H

AU - Smith, Richard J H

AU - Stratakis, Constantine A

AU - Weil, Dominique

AU - Petit, Christine

AU - Hildebrandt, Friedhelm

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

KW - Humans

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Base Sequence

KW - Gene Expression Regulation, Developmental

KW - Protein Structure, Tertiary

KW - Nuclear Proteins

KW - Cell Line

KW - Protein Binding

KW - Macromolecular Substances

KW - Genes, Reporter/genetics

KW - Mutation/genetics

KW - Trans-Activators/metabolism

KW - Branchio-Oto-Renal Syndrome/genetics

KW - DNA/genetics/metabolism

KW - Homeodomain Proteins/chemistry/genetics/metabolism

KW - Intracellular Signaling Peptides and Proteins

KW - Protein Tyrosine Phosphatases

KW - Humans

KW - Amino Acid Sequence

KW - Molecular Sequence Data

KW - Base Sequence

KW - Gene Expression Regulation, Developmental

KW - Protein Structure, Tertiary

KW - Nuclear Proteins

KW - Cell Line

KW - Protein Binding

KW - Macromolecular Substances

KW - Genes, Reporter/genetics

KW - Mutation/genetics

KW - Trans-Activators/metabolism

KW - Branchio-Oto-Renal Syndrome/genetics

KW - DNA/genetics/metabolism

KW - Homeodomain Proteins/chemistry/genetics/metabolism

KW - Intracellular Signaling Peptides and Proteins

KW - Protein Tyrosine Phosphatases

M3 - SCORING: Journal article

VL - 101

SP - 8090

EP - 8095

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 21

M1 - 21

ER -