#610896
BRANCHIOOTORENAL SYNDROME 2; BOR2

Phenotype Gene Relationships
Location Phenotype Phenotype
MIM number
Gene/Locus Gene/Locus
MIM number
19q13.32 Branchiootorenal syndrome 2 610896 SIX5 600963

TEXT
A number sign (#) is used with this entry because this form of branchiootorenal syndrome (BOR2) can be caused by mutation in the SIX5 gene (600963). Another form, BOR1 (113650), is caused by mutation in the EYA1 gene (601653).

For a phenotypic description and a discussion of genetic heterogeneity of the branchiootorenal syndrome, see BOR1 (113650).

Clinical Features
Hoskins et al. (2007) reported 5 patients with a clinical diagnosis of BOR who carried heterozygous mutations in the SIX5 gene. One of the patients had bilateral dysplastic kidneys and a right preauricular tag but normal hearing. A second had bilateral cervical fistulae; right-sided hemifacial microsomia, preauricular sinus, and pinna malformation; hearing loss in both ears, with the right side more affected than the left; and bilateral renal dysplasia with diminished renal function. Another patient had cervical fistulae and hypoplastic kidneys, and a fourth had cervical fistulae, moderate to severe hearing loss in both ears, and left renal agenesis with a hypoplastic right kidney. Clinical data was unavailable in the fifth subject.

Molecular Genetics
Hoskins et al. (2007) identified 4 mutations in the SIX5 gene (600963) as a novel cause of BOR in 5 patients. The SIX5 gene was considered a good candidate for BOR owing to its similarity to SIX1 (601205), mutations in which cause branchiootic syndrome-3 (608389), and data on C. elegans on its direct interaction with eya-1 (601653), mutations in which also cause BOR (Li et al., 2004).

REFERENCES
1. Hoskins, B. E., Cramer, C. H., II, Silvius, D., Zou, D., Raymond, R. M., Jr., Orten, D. J., Kimberling, W. J., Smith, R. J. H., Weil, D., Petit, C., Otto, E. A., Xu, P.-X., Hildebrandt, F. Transcription factor SIX5 is mutated in patients with branchio-oto-renal syndrome. Am. J. Hum. Genet. 80: 800-804, 2007. [PubMed: 17357085, related citations] [Full Text: Elsevier Science, Pubget]

2. Li, S., Armstrong, C. M., Bertin, N., Ge, H., Milstein, S., Boxem, M., Vadalian, P. O., Han, J. D., Chesneau, A., Hao, T., Goldberg, D. S., Li, N., and 36 others. A map of the interactome network of the metazoan C. elegans. Science 303: 540-543, 2004. [PubMed: 14704431, related citations] [Full Text: HighWire Press, Pubget]

Creation Date: Victor A. McKusick : 3/28/2007
Edit History: terry : 01/27/2012
alopez : 3/29/2007