【摘要】 目的 对一例非综合征型耳聋家系进行临床特征描述及遗传学分析，找出相关基因及突变位点，为临床诊疗奠定基础。方法 对家系成员进行病史采集、体格及听力学检查，取外周血，先对四个耳聋基因（GJB2、SLC26A4、GJB3和MT-RNR1）的21个常见位点进行检测；如未见突变，则对这四个基因进行全测序；如仍未发现致病突变，则进行全外显子检测（WES）和耳聋基因Panel-V3检测，并对检测结果进行分析和验证。通过Real-time PCR检测Polr1d的mRNA在C57BL/6J小鼠不同发育时期耳蜗组织中的表达。结果 该家系患者表现为非综合征型感音神经性聋，患者POLR1D(RNA聚合酶Ⅰ和Ⅲ亚基D)出现c.52A>G(p.M18V)杂合突变，该位点在多个物种中高度保守，该基因mRNA在各发育期小鼠耳蜗组织中均有表达。结论 本研究在一个非综合征型耳聋家系中发现了POLR1D的一个新突变位点，此突变可能是该耳聋家系的致病因素，这与以往报道的POLR1D突变引起的疾病类型不同，该发现为研究耳聋发生机制和诊疗提供了新思路。更多还原

【Abstract】 Objective To describe clinical characteristics and genetic etiology of non-syndromic deafness in a family. Methods Medical history, physical and audiological examination and peripheral blood collection were completed on members of the family. Twenty one loci of the GJB2, SLC26A4, GJB3 and MT-RNR1 genes commonly involved in deafness were screened and full sequencing of the four genes were completed if no mutations were identified, followed by whole-exon sequencing(WES) and deafness gene Panel-V3 test with validation if no pathogenic variants were found in full sequencing. Real-time PCR was used to detect expression of Polr1d mRNA in cochlear tissues in C57BL/6J mice at different development stages. Results Patients in this family presented with non-syndromic sensorineural deafness with c.52A>G(p.M18V) variant in POLR1D. This mutation is highly conserved across several species. Polr1d mRNA was expressed in all cochlear tissues in C57BL/6J mice at different developmental stages. Conclusion A new mutation in POLR1D has been identified in a family with non-syndromic sensorineural deafness, which may be the pathogenic factor for the family and different from diseases caused by POLR1D mutations reported previously. This finding provides a new mechanism of deafness and a new diagnosis.更多还原