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Nonsense mutation of the stereociliar membrane protein gene PTPRQ in human hearing loss DFNB84
  1. Hashem Shahin1,
  2. Michael Rahil2,
  3. Amal Abu Rayan1,
  4. Karen B Avraham3,
  5. Mary-Claire King4,
  6. Moien Kanaan1,
  7. Tom Walsh4
  1. 1Department of Life Sciences, Bethlehem University, Bethlehem, Palestinian National Authority
  2. 2Dar Al-Kalima Health and Wellness Center, Bethlehem, Palestinian National Authority
  3. 3Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
  4. 4Department of Medicine, Division of Medical Genetics, University of Washington, Seattle, WA, USA
  1. Correspondence to Dr Tom Walsh, University of Washington, Division of Medical Genetics, Box 357720, Seattle, WA 98195, USA; twalsh{at}


Background Moderate to severe prelingual hearing impairment (DFNB84) was observed in an extended consanguineous Palestinian kindred. All affected relatives shared a 12.5 MB homozygous haplotype on chromosome 12q21 with lod score 4.30. This homozygous region harbours the protein tyrosine phosphatase receptor Q gene PTPRQ, which is known to be essential to hearing in mouse.

Methods Candidate genes in the 12.5 MB homozygous region were characterized genomically and sequenced in deaf and hearing relatives in the family.

Results Sequence of PTPRQ in affected individuals in the extended kindred revealed c.1285C→T, leading to p.Gln429Stop. This nonsense mutation co-segregated with hearing loss in the family and was homozygous in all affected relatives. The mutation did not appear among 288 Palestinian controls (576 chromosomes), all adults with normal hearing. No homozygous mutations in PTPRQ appeared in any of 218 other probands with hearing loss.

Conclusion Identification of the DFNB84 gene represents the first identification of PTPRQ mutation in human hearing loss.

  • Deafness
  • homozygosity mapping
  • mutation

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  • Funding NIH.

  • Competing interests None

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the Human Subjects Committee of Bethlehem University and by the Human Subjects Division of the University of Washington.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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