Journal of Molecular Medicine

, Volume 83, Issue 7, pp 553–560

Two families with nonsyndromic low-frequency hearing loss harbor novel mutations in Wolfram syndrome gene 1

  • Nicolas Gürtler
  • Yuil Kim
  • Anand Mhatre
  • Christoph Schlegel
  • Adolf Mathis
  • Robert Daniels
  • Clough Shelton
  • Anil K. Lalwani
Original Article

DOI: 10.1007/s00109-005-0665-1

Cite this article as:
Gürtler, N., Kim, Y., Mhatre, A. et al. J Mol Med (2005) 83: 553. doi:10.1007/s00109-005-0665-1

Abstract

Although hereditary hearing loss is highly heterogeneous, only a few loci have been implicated with low-frequency hearing loss. Mutations in one single gene, Wolfram syndrome 1 (WFS1), have been reported to account for most familial cases with this type of hearing impairment. This study was conducted to determine the cause of nonsyndromic low-frequency hereditary hearing impairment in two large families. Two large families from Switzerland and United States with low-frequency hearing loss were identified. Genomewide linkage analysis was performed followed by mutation screening in the candidate gene WFS1 with direct DNA sequencing and restriction fragment analysis. Both families were linked to DFNA6/14/38 with lod scores>3. Two novel heterozygous missense mutations in WFS1 were identified: c.2311G>C leading to p.D771H in the Swiss family and c.2576G>C leading to p.R859P in the US family. The sequence alteration was absent in 100 control chromosomes. Nonsyndromic low-frequency hereditary hearing impairment seems to be predominantly a monogenic disorder due to WFS1. We confirm that most mutations in WFS1 associated with isolated low-frequency hearing loss are clustered in the C-terminal protein domain coded by exon 8.

Keywords

Wolfram syndrome gene 1Nonsyndromic hereditary hearing impairmentLow-frequency hearing loss

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Nicolas Gürtler
    • 1
    • 2
  • Yuil Kim
    • 2
  • Anand Mhatre
    • 2
    • 3
  • Christoph Schlegel
    • 4
  • Adolf Mathis
    • 4
  • Robert Daniels
    • 5
    • 6
  • Clough Shelton
    • 5
    • 6
  • Anil K. Lalwani
    • 2
    • 3
    • 7
  1. 1.Hals-Nasen-Ohren-KlinikKantonsspital AarauAarauSwitzerland
  2. 2.Laboratory of Molecular Otology, Epstein Laboratories, Department of Otolaryngology–Head and Neck SurgeryUniversity of California–San FranciscoSan FranciscoUSA
  3. 3.Laboratory of Molecular Otology, Department of OtolaryngologyNew York UniversityNew YorkUSA
  4. 4.Hals-Nasen-Ohren-KlinikKantonsspital LuzernLucerneSwitzerland
  5. 5.Department of OtolaryngologyUniversity of UtahSalt Lake CityUSA
  6. 6.Michigan Ear Center Department of SurgeryMichigan State UniversityEast LansingUSA
  7. 7.Department of OtolaryngologyNYU School of MedicineNew YorkUSA