Nonsense mutation of the stereociliar membrane protein gene PTPRQ in human hearing loss DFNB84
Nonsense mutation of the stereociliar membrane protein gene PTPRQ in human hearing loss DFNB84
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DOI：
10.1136/jmg.2009.075697
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发表时间：
2010-09-01
影响因子：
4
通讯作者：
Walsh, Tom
中科院分区：
文献类型：
--
作者：
Shahin, Hashem;Rahil, Michael;Walsh, Tom
背景中度至重度语前听力损伤（DFNB 84）在一个扩展的巴勒斯坦血缘亲属中观察到。所有受影响的亲属在染色体12q21上共享12.5MB纯合单倍型，lod评分为4.30。方法对12.5MB纯合区域内的候选基因进行基因组学分析，并对该家系耳聋和听力正常的亲属进行测序。这种无义突变与家族中的听力损失共分离，并且在所有受影响的亲属中均为纯合子。在288名巴勒斯坦对照组（576条染色体）中没有出现突变，所有成年人都有正常的听力。结论DFNB 84基因是首次发现PTPRQ基因突变的人类听力损失患者。
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.