SIX1 mutation screening in 247 branchio-oto-renal syndrome families: A recurrent missense mutation associated with BOR

Amit Kochhar, Dana J. Orten, Jessica L. Sorensen, Stephanie M. Fischer, Cor W.R.J. Cremers, William J. Kimberling, Richard J.H. Smith

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

Branchio-oto-renal syndrome (BOR) is a clinically heterogeneous autosomal dominant form of syndromic hearing loss characterized by variable hearing impairment, malformations of the pinnae, the presence of branchial arch remnants, and various renal abnormalities. Both EYA1 and SIX1 are expressed in developing otic, branchial and renal tissue. Consistent with this expression pattern, mutations in both genes cause BOR syndrome. Mutations in EYA1 are found in approximately 40% of patients with the BOR phenotype, however, the role of SIX1 is much lower. To date only three different SIX1 mutations have been described in BOR patients. The current screen of 247 BOR families detected five novel SIX1 mutations (c.50T>A, c.218A>C, c.317T>G, c.329G>A, c.334C>T) and one previously reported mutation (c.328C>T) seen in 5 unrelated families. All mutations are within the protein-binding Six domain. Phenotypic variability was high in these BOR families. Seven of the eight known SIX1 mutations are missense and the one in frame deletion is predicted to be functionally similar. The wide phenotypic variability precludes making genotype-phenotype correlations at this time.

Original languageEnglish (US)
Pages (from-to)565
Number of pages1
JournalHuman mutation
Volume29
Issue number4
DOIs
StatePublished - 2008

Keywords

  • BOR
  • Branchio-oto-renal syndrome
  • CpG dinucleotide
  • Genetic heterogeneity
  • Recurrent mutation
  • SIX1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Kochhar, A., Orten, D. J., Sorensen, J. L., Fischer, S. M., Cremers, C. W. R. J., Kimberling, W. J., & Smith, R. J. H. (2008). SIX1 mutation screening in 247 branchio-oto-renal syndrome families: A recurrent missense mutation associated with BOR. Human mutation, 29(4), 565. https://doi.org/10.1002/humu.20714