Ruf et al. (2004) located the SIX1, SIX4 (606342), and SIX6 (606326) genes, which act within a genetic network of EYA and PAX genes to regulate organogenesis, within a 33-Mb critical interval on chromosome 14q23. By direct sequencing ... Ruf et al. (2004) located the SIX1, SIX4 (606342), and SIX6 (606326) genes, which act within a genetic network of EYA and PAX genes to regulate organogenesis, within a 33-Mb critical interval on chromosome 14q23. By direct sequencing of exons in these genes, they identified 2 different mutations in the SIX1 gene in 3 kindreds with branchiootic syndrome-3 (601205.0001-601205.0002). In 7 affected individuals from a large 5-generation Danish family with branchiootic syndrome, Sanggaard et al. (2007) identified heterozygosity for a missense mutation in the SIX1 gene (601205.0004). All affected individuals had hearing impairment, and some had branchial and preauricular defects. There were no subjective complaints indicating renal disease, and no renal anomalies were detected in the 3 affected individuals who underwent renal ultrasound. The mutation was not found in unaffected family members or in 140 control chromosomes.