206例非综合征型听障儿童听力学及基因型分析
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摘要
目的客观评估非综合征型耳聋患者的听力,并分析其可能的致聋遗传病因。方法对广州某聋校206例(412耳)非综合征型耳聋患者行纯音听阈、声导抗、睡眠状态下的听性脑干反应(ABR)、听觉多频稳态(ASSR)阈值测试;应用基因芯片技术进行国人热点变异基因GJB2、GJB3、SLC26A4、Mt-RNR1检测,结合病史和客观检测结果进行分析。结果(1)听力学:纯音听阈检测示被试均为重度以上感音神经性聋,声导抗双耳均为A型图;仅18例(32耳)反应阈值为90 dB nHL,其余均未引出分化明显的各波形;ASSR在0.5,1,2,4 kHz频率处的阈值与同频率纯音听阈测定(pure tone threshold andiometry,ptA)阈值比较,不同性别、左右耳均呈线性正相关;(2)基因型:携带GJB2致聋基因者16例;携带SLC26A4致聋基因者25例,携带Mt--RNR1致聋基因m.1555A>G者1例。携带耳聋热点基因与基因芯片没有检测出热点基因患者的不同听力损失程度例数对比,差异无明显统计学意义;纯合变异与杂合变异患者的听力差异无统计学意义。结论听力学检查与基因筛查能够迅速、客观、可靠的评估非综征性耳聋患者的听力情况与可能病因。GJB2、SLC26A4仍是此聋校的常见致聋基因。
Objective To evaluate the hearing threshold of nonsyndromic hearing impairment individuals and analyze the probable molecular etiology basis for auditory test combined with gene screening. Methods A total of 206 nonsyndromic hearing impairment individuals(412 ears) received pure tone audiometry, tympanogram, ASSR and ABR under sleep conditions, and tested with an allele-specific PCR-based universal array. Results PTA thresholds showed all of the individuals were severe or above sensorineural hearing loss and tympanogram were type A. ABR showed that only18 individuals(32 ears) had a response threshold of 90 dB nHL. ASSR threshold was compared with PTA thresholds at0.5,1.0,2.0,4.0 Hz.The ASSR threshold was found to be positively correlated with the PTA threshold. Genotype 42 NSHI patients carried pathogenic mutations in the screening chip in the population studied. Of the 42 screened carriers, 16 patients(7.77%) harbored GJB2 mutation and 25(12.14%) were SLC26 A4. Only one was homoplasmy mutation carriers of mitochondrial MT-RNR1 gene. The degree of hearing loss in those hot genes mutation group, compaired with others,showed no statistical significance(P>0.05). Conclusion Audiology combined with gene array screeing may serve as a reliable objective rapid measurement in detecting nonsyndromic hearing impairment individuals as well as the probable molecular etiology. GJB2 and SLC26 A4 were still the common genes in this deaf school according to this gene chip.
Objective To evaluate the hearing threshold of nonsyndromic hearing impairment individuals and analyze the probable molecular etiology basis for auditory test combined with gene screening. Methods A total of 206 nonsyndromic hearing impairment individuals(412 ears) received pure tone audiometry, tympanogram, ASSR and ABR under sleep conditions, and tested with an allele-specific PCR-based universal array. Results PTA thresholds showed all of the individuals were severe or above sensorineural hearing loss and tympanogram were type A. ABR showed that only18 individuals(32 ears) had a response threshold of 90 dB nHL. ASSR threshold was compared with PTA thresholds at0.5,1.0,2.0,4.0 Hz.The ASSR threshold was found to be positively correlated with the PTA threshold. Genotype 42 NSHI patients carried pathogenic mutations in the screening chip in the population studied. Of the 42 screened carriers, 16 patients(7.77%) harbored GJB2 mutation and 25(12.14%) were SLC26 A4. Only one was homoplasmy mutation carriers of mitochondrial MT-RNR1 gene. The degree of hearing loss in those hot genes mutation group, compaired with others,showed no statistical significance(P>0.05). Conclusion Audiology combined with gene array screeing may serve as a reliable objective rapid measurement in detecting nonsyndromic hearing impairment individuals as well as the probable molecular etiology. GJB2 and SLC26 A4 were still the common genes in this deaf school according to this gene chip.
引文
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[7]Huang S,Huang B,Wang G,et al.the relationship between the p.V37I mutation in GJB2 and hearing phenotypes in Chinese individuals[J].plos One,2015,10(6):e.0129662.
[8]Luo S,Valencia CA,Zhang J,et al.Biparental Inheritance of Mitochondrial DNA in Humans[J].proceedings of the National Academy of Sciences,2018,115(51):13039-13044.
[9]王斌,宋凡,卢星,等.耳聋基因相关感音神经性聋患儿临床特点分析[J].听力学及言语疾病杂志,2017,25(5):472-475.
[10]胡书君,厉建强,张鹏,等.新生儿听力与聋病易感基因联合筛查的临床研究[J].听力学及言语疾病杂志,2010,18(3):222-224.
[2]杨锴,戚红,黄莎莎,等.孕期遗传性耳聋热点致病基因突变筛查及高风险妊娠的产前诊断[J].中华耳鼻咽喉头颈外科杂志,2018,53(9):645-649.
[3]李超,王永华.极重度听损大前庭水管综合征婴幼儿患者ABR和ASSR结果分析[J].中国听力语言康复科学杂志,2014,12(5):344-346.
[4]闻雨婷.听觉稳态的技术革新[J].听力与言语疾病杂志,2010,18(4):395-397.
[5]张森,王斌全,皇甫辉.多频听觉稳态反应研究进展[J].听力与言语疾病杂志,2006,14(4):316-318.
[6]王国建,戴朴,韩东一,等.基因芯片技术在非综合征性耳聋快速基因诊断中的应用研究[J].中华耳科学杂志,2008,6(1):61-66.
[7]Huang S,Huang B,Wang G,et al.the relationship between the p.V37I mutation in GJB2 and hearing phenotypes in Chinese individuals[J].plos One,2015,10(6):e.0129662.
[8]Luo S,Valencia CA,Zhang J,et al.Biparental Inheritance of Mitochondrial DNA in Humans[J].proceedings of the National Academy of Sciences,2018,115(51):13039-13044.
[9]王斌,宋凡,卢星,等.耳聋基因相关感音神经性聋患儿临床特点分析[J].听力学及言语疾病杂志,2017,25(5):472-475.
[10]胡书君,厉建强,张鹏,等.新生儿听力与聋病易感基因联合筛查的临床研究[J].听力学及言语疾病杂志,2010,18(3):222-224.