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.
- homozygosity mapping
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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.