Nonsense mutation of the stereociliar membrane protein gene PTPRQ in human hearing loss DFNB84

作者：Shahin Hashem; Rahil Michael; Abu Rayan Amal; Avraham Karen B; King Mary Claire; Kanaan Moien; Walsh Tom^*

来源：Journal of Medical Genetics, 2010, 47(9): 643-645.

DOI：10.1136/jmg.2009.075697

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 PTPRO, 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 PTPRO 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.

• 出版日期2010-9