Identification of a novel compound heterozygous mutation in PTPRQ in a DFNB84 family with prelingual sensorineural hearing impairment
Identification of a novel compound heterozygous mutation in PTPRQ in a DFNB84 family with prelingual sensorineural hearing impairment
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DOI：
10.1007/s00438-014-0979-1
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发表时间：
2015-06-01
影响因子：
3.1
通讯作者：
Wang, Lei
中科院分区：
文献类型：
--
作者：
Sang, Qing;Mei, Honglin;Wang, Lei
听力损失的患病率为0.1%，是最常见的感官障碍之一，影响着世界各地数百万人。识别与耳聋相关的基因或基因座可能有助于耳聋的基础研究和临床翻译研究。PTPRQ基因编码蛋白酪氨酸磷酸酶受体Q，它是哺乳动物耳蜗轴连接器的形成和毛束的正常成熟和发育所必需的。在这里，我们介绍了一个常染色体隐性遗传性非综合征性听力障碍哈萨克族家庭的遗传和分子特征，DFNB84。利用全外显子测序，我们鉴定了两个突变，这两个突变共同形成了PTPRQ中一个新的复合杂合突变。Sanger测序证实，受影响的成员同时遗传了c.16_17insT(L8fsX18)和c.2714delA(E909fsX922)突变。这两种突变都会导致蛋白质的移码和截断。在这个家庭中，新的复合杂合突变与听力损失共分离，在200名健康的哈萨克人对照中或在任何公共数据库中都没有发现这两个突变。在这项研究中，我们发现了与DFNB84相关的PTPRQ的新突变。这是中国家族性耳聋患者中发现的第三例PTPRQ基因突变，也是首例家族性耳聋患者。新发现的PTPRQ基因突变进一步证实了PTPRQ基因在听力发育和听觉功能中的重要作用。我们的数据为更好地了解DFNB84的基因-表型提供了额外的分子信息。
With a prevalence of 0.1 %, hearing loss is among the most common sensory impairments and affects several million people around the world. Identification of deafness-related genes or loci may facilitate basic research and clinical translational research of the disorder. The PTPRQ gene encodes protein tyrosine phosphatase receptor Q, which is required for the formation of shaft connectors and the normal maturation and development of hair bundles in the mammalian cochlea. Here, we present the genetic and molecular characteristics of a Kazakh family with an autosomal recessive non-syndromic hearing impairment, DFNB84. Using whole-exome sequencing, we identified two mutations that together form a novel compound heterozygous mutation in PTPRQ. Sanger sequencing confirmed that the affected members inherited both the c.16_17insT (L8fsX18) and c.2714delA (E909fsX922) mutations. Both mutations lead to a frameshift and a truncated form of the protein. The novel compound heterozygous mutation co-segregated with hearing loss in this family, and neither of the two mutations was found in 200 healthy Kazakh controls or in any of the public databases. In the study, we identified novel mutations in PTPRQ responsible for DFNB84. This is the third report of PTPRQ mutations involved in deafness and the first report of familial deafness in China. The identification of novel mutations in PTPRQ presented here further confirms the essential role of PTPRQ in hearing development and auditory function. Our data provide additional molecular information for establishing a better genotype-phenotype understanding of DFNB84.