Mutational analysis of EYA1, SIX1 and SIX5 genes and strategies for management of hearing loss in patients with BOR/BO syndrome

PLoS One. 2013 Jun 28;8(6):e67236. doi: 10.1371/journal.pone.0067236. Print 2013.

Abstract

Background: Branchio-oto-renal (BOR) or branchio-otic (BO) syndrome is one of the most common forms of autosomal dominant syndromic hearing loss. Mutations in EYA1, SIX1 and SIX5 genes have been associated with BOR syndrome. In this study, clinical and genetic analyses were performed in patients with BOR/BO syndrome focusing on auditory manifestations and rehabilitation.

Methods: The audiologic manifestations were reviewed in 10 patients with BOR/BO syndrome. The operative findings and hearing outcome were analyzed in patients who underwent middle ear surgeries. The modality and outcome of auditory rehabilitation were evaluated. Genetic analysis was performed for EYA1, SIX1, and SIX5 genes.

Results: All patients presented with mixed hearing loss. Five patients underwent middle ear surgeries without successful hearing gain. Cochlear implantation performed in two patients resulted in significant hearing improvement. Genetic analysis revealed four novel EYA1 mutations and a large deletion encompassing the EYA1 gene.

Conclusions: Auditory rehabilitation in BOR/BO syndrome should be individually tailored keeping in mind the high failure rate after middle ear surgeries. Successful outcome can be expected with cochlear implantations in patients with BOR/BO syndrome who cannot benefit from hearing aids. The novel EYA1 mutations may add to the genotypic and phenotypic spectrum of BOR syndrome in the East Asian population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alternative Splicing
  • Base Sequence
  • Branchio-Oto-Renal Syndrome / diagnostic imaging
  • Branchio-Oto-Renal Syndrome / genetics*
  • Branchio-Oto-Renal Syndrome / physiopathology
  • Branchio-Oto-Renal Syndrome / therapy
  • Child
  • DNA Mutational Analysis
  • Disease Management
  • Ear, Middle / surgery
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • HeLa Cells
  • Hearing Loss / diagnostic imaging
  • Hearing Loss / genetics*
  • Hearing Loss / physiopathology
  • Hearing Loss / therapy
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Point Mutation
  • Polymorphism, Genetic
  • Protein Tyrosine Phosphatases / genetics*
  • Protein Tyrosine Phosphatases / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiography
  • Sequence Deletion
  • Temporal Bone / abnormalities
  • Temporal Bone / diagnostic imaging
  • Young Adult

Substances

  • Homeodomain Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • SIX1 protein, human
  • SIX5 protein, human
  • EYA1 protein, human
  • Protein Tyrosine Phosphatases

Grants and funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2012R1A1A1015761) and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0028066). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.