耳聋基因panel在耳聋基因诊断中的临床应用

doi:10.6040/j.issn.1673-3770.0.2022.190

摘要/Abstract

摘要： 目的探讨耳聋基因panel技术在耳聋患者基因诊断中的应用。方法 40例耳聋患者首先采用荧光定量PCR结合Sanger测序法检测4个常见耳聋基因的25个位点突变,初检结果单杂合致病突变者行耳聋基因单基因测序或耳聋基因panel检测;初检结果未发现耳聋基因致病性突变者直接行耳聋基因panel检测。16例患者行父母耳聋基因溯源验证。结果 40例患者中,耳聋基因筛查检出GJB2基因纯合或复合杂合突变8例、单杂合突变2例,SLC26A4基因纯合突变1例、单杂合突变2例。4例单杂合突变检出者接受进一步的耳聋单基因或耳聋基因panel测序,其中2例分别检出GJB2基因c.235delC/c.610delC及c.235delC/c.109G>A复合杂合突变,2例检出SLC26A4基因c.919-2A>G/c.1548_1549insC复合杂合突变。27例初检结果阴性患者接受了进一步的耳聋基因panel检测,检出GJB2基因c.109G>A纯合突变4例和c.571T>C/c.G109A复合杂合突变1例,MYO7A基因c.397dupC/c.3484A>T复合杂合突变1例,MYO15A 基因c.4779+2T>C/c.5008-2A>G复合杂合突变1例,ACTG1基因c.118C>T单杂合突变1例,CDH23基因c.1765G>A/c.6504T>A及c.6049G>A/c.7225-1G>A复合杂合突变各1例。在16例行父母溯源的耳聋患者中,15例患者耳聋基因突变分别遗传自其父母。结论对于耳聋基因热点突变检测结果阴性的耳聋患者,应用耳聋基因panel能有效提高遗传性致病基因检出效率,为其遗传学诊断和临床治疗提供依据。

关键词: 耳聋, GJB2基因, SLC26A4基因, MYO7A基因, 耳聋基因panel

Abstract: Objective This study aimed to explore the application of the deafness gene panel in the genetic analysis of patients with hearing loss. Methods The combination of real-time polymerase chain reaction(PCR)and Sanger sequencing was used to identify the 25 mutations of four common deafness genes in 40 deaf patients. Patients with heterozygous mutations, detected via deafness gene sequencing, underwent further single deafness gene sequencing or target gene panel testing. Those with negative real-time PCR results underwent target gene panel testing. The parents of the 16 patients underwent genetic analysis to identify inherited mutations. Results Among the 40 patients, there were eight patients with a homozygous or compound heterozygous mutation in the GJB2 gene and two patients with a single heterozygous mutation, according to the deafness genetic screening. Moreover, one patient had a homozygous mutation, while two had a single heterozygous mutation in the SLC26A4 gene. The four patients with single heterozygous mutations underwent further single deafness gene sequencing or target gene panel testing. Two patients had the compound heterozygous mutation, GJB2 c.235delC/c.610delC or c.235delC/c.109G>A. Meanwhile, two patients had SLC26A4 c.919-2A>G/c.1548_1549insC. Among the 27 patients with negative real-time PCR results, there were four patients with the homozygous mutation, GJB2 c.109G>A, one patient with c.571T>C/c.G109A, one patient with MYO7A c.397dupC/c.3484A>T, one patient with MYO15A c.4779+2T>C/c.5008-2A>G, and one patient with the heterozygous mutation, ACTG1 c.118C>T, based on target gene panel testing. Additionally, there were two patients with the compound heterozygous mutations, CDH23 c.1765G>A/c.6504T>A and c.6049G>A/c.7225-1G>A, respectively. Among the 16 patients, 15 inherited the deafness genetic mutations from their parents, according to the genetic analysis. Conclusion The deafness gene panel improved the genetic diagnostic rate among deaf patients with negative results of hotspot deafness gene mutations.

Key words: Deafness, GJB2 gene, SLC26A4 gene, MYO7A gene, Deafness gene panel

中图分类号:

R764.43

张艳红, 李娟娟, 曾宪海, 缑灵山, 王朝霞, 魏建芳, 马芳, 邱书奇. 耳聋基因panel在耳聋基因诊断中的临床应用[J]. 山东大学耳鼻喉眼学报, 2022, 36(4): 27-34.

ZHANG Yanhong, LI Juanjuan, ZENG Xianhai, GOU Lingshan, WANG Zhaoxia, WEI Jianfang, MA Fang, QIU Shuqi. Clinical application of target gene panel testing in genetic diagnosis of deafness[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2022, 36(4): 27-34.

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