ArticleProceedings of the National Academy of Sciences of the United States of America2004
SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
199 citing papers in PubMed, 417 citations in OpenAlex.
- A Comprehensive Assessment of the Shared Genetic Architecture between Myopia and Open-Angle Glaucoma.Ophthalmology science · 2026Article
- Unveiling the Prevalence and Surgical Burden of Neurocristopathies: A Scoping Review and Statistical Analysis.Research square · 2026Article
- SIX1 branchio-oto-renal syndrome variants have different effects on embryonic craniofacial gene expression and cartilage formation.Development (Cambridge, England) · 2026Article
- A review of congenital anomalies of the kidney and urinary tract (CAKUT) in Africa.Annals of medicine and surgery (2012) · 2026Review
- Branchio-oto-renal syndrome: a narrative review.Childhood kidney diseases · 2026Review
- Prenatal phenotypic delineation of a de novo EYA1 likely pathogenic variant in branchio-oto-renal syndrome.BMC medical genomics · 2026Article
- Renal dysplasia development and chronic kidney disease.Pediatric research · 2025Review
- IPSC-induced podocytes from a BORS patient with EYA1 gene mutation showed glucocorticoid-resistant and cytoskeletal rearrangement.Cellular and molecular life sciences : CMLS · 2025Article
- Translational strategies to uncover the etiology of congenital anomalies of the kidney and urinary tract.Pediatric nephrology (Berlin, Germany) · 2025Review
- Sine oculis homeobox homolog family function in gastrointestinal cancer: Progression and comprehensive analysis.World journal of clinical oncology · 2025Review
- SIX transcription factors are necessary for the activation of DUX4 expression in facioscapulohumeral muscular dystrophy.Skeletal muscle · 2024Article
- Pathogenic PHIP Variants are Variably Associated With CAKUT.Kidney international reports · 2024Article
- Genomic Landscape of Branchio-Oto-Renal Syndrome through Whole-Genome Sequencing: A Single Rare Disease Center Experience in South Korea.International journal of molecular sciences · 2024Article
- Targeting sine oculis homeoprotein 1 (SIX1): A review of oncogenic roles and potential natural product therapeutics.Heliyon · 2024Review
- CRISPR-based editing strategies to rectifyMolecular therapy. Nucleic acids · 2024Article
- All eyes on Eya: A unique transcriptional co-activator and phosphatase in cancer.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- Using Xenopus to discover new candidate genes involved in BOR and other congenital hearing loss syndromes.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2024Review
- Novel likely pathogenic variant in the EYA1 gene causing Branchio oto renal syndrome and the exploration of pathogenic mechanisms.BMC medical genomics · 2024Article
- Genetics and Epigenetics in the Genesis and Development of Microtia.The Journal of craniofacial surgery · 2024Article
- The genetic etiologies of bilateral renal agenesis.Prenatal diagnosis · 2024Review
139 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 1 institution in 1 country.
Funding
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.