A novel dominant mutation in SIX1, affecting a highly conserved residue, result in only auditory defects in humans

Eur J Med Genet. Sep-Oct 2011;54(5):e484-8. doi: 10.1016/j.ejmg.2011.06.001. Epub 2011 Jun 15.

Abstract

Branchio-oto-renal (BOR) and Branchio-otic (BO) syndromes are dominant disorders characterized by variable hearing impairment (HI) and branchial defects. BOR includes additional kidney malformations. BO/BOR syndromes are genetically heterogeneous and caused by mutations in EYA1 and SIX1 genes. Mutation in SIX1 is responsible also for DFNA23, a locus for non-syndromic HI. Strikingly, the severity of the phenotype did not seem to correlate with the type of SIX1 mutation. Herein, we identified a novel mutation in SIX1 (p.E125K) in a Tunisian family with variable HI and preauricular pits. This mutation is located at the same position as the mutation identified in the Catwhesel (Cwe) mouse. No renal and branchial defects were observed in our family nor in Cwe/+ mice. A homology model revealed that the replacement of the Glutamate by a Lysine alters the electrostatic potential surface propriety which may affect the DNA-binding activity.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Base Sequence
  • Branchio-Oto-Renal Syndrome / genetics
  • Conserved Sequence
  • Ear / abnormalities*
  • Female
  • Hearing Loss / genetics*
  • Homeodomain Proteins / genetics*
  • Humans
  • Kidney / abnormalities
  • Male
  • Microsatellite Repeats / genetics
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Protein Conformation
  • Sequence Alignment

Substances

  • Homeodomain Proteins
  • SIX1 protein, human