先天性耳聋儿童分频听性脑干反应检测和多位点耳聋基因筛查

Application of frequency-division auditory brainstem response and multilocus deafness gene screening in children with congenital deafness

目的:分频听性脑干反应(Chirp-ABR)检测和多位点耳聋基因筛查在先天性耳聋儿童中的应用。方法:选择2019年5月至2021年5月确诊的先天性耳聋患儿116例,微阵列芯片法检测外周血4个耳聋基因9个SNP位点,包括GJB2(35delG、176del16、235delC和299delAT)、GJB3(C538C>T)、SLC26A4(2168A>G和IVS7-2A>G)和线粒体12S rRNA(1494C>T和1555A>G)。行Chirp-ABR和多频听觉稳态反应(ASSR)检查,判断听力受损程度。结果:116例中共73例(62.9%)检测到耳聋基因突变,其中GJB2基因突变21例(8例35delG、7例176del16、4例235delC、2例299delAT),GJB3突变(C538C>T)6例,SLC26A4突变20例(11例2168A>G,9例IVS7-2A>G),线粒体12S rRNA突变15例(10例1494C>T,5例1555A>G),GJB2+SLC26A4双突变7例,GJB3+线粒体12S rRNA双突变4例。与无基因突变组(n=43)比较,基因突变组患儿听力受损更严重,0.5、1.0、2.0和4.0 kHz测试频率下Chirp-ABR和ASSR反应阈更高(P<0.05)。基因突变组各测试频率下Chirp-ABR和ASSR反应阈有较好的相关性(rS=0.517、0.608、0.515、0.651,P<0.001)。单位点突变与双位点突变组比较,4个单位点突变组比较,患儿听力受损程度、各频率下Chirp-ABR和ASSR反应阈差异均无统计学意义(P>0.05)。结论:先天性耳聋儿童4个耳聋基因的突变率较高,以单位点突变为主。有耳聋基因突变的患儿听力受损更严重。

Aim:To investigate the application of frequency-division chirp evoked auditory brainstem response(Chirp-ABR)and multilocus deafness gene screening in children with congenital deafness.Methods:A total of 116 children with congenital deafness from May 2019 to May 2021 were selected.Nine SNP of 4 deafness genes in the peripheral blood were detected by microarray method,including GJB2(35delG,176del16,235delC and 299delAT),GJB3(C538C>T),SLC26A4(2168A>G and IVS7-2A>G)and mitochondrial 12S rRNA(1494C>T and 1555A>G).Chirp-ABR and multi-frequency auditory steady-state response(ASSR)were used to determine the degree of hearing impairment.Results:Deafness gene mutations were detected in 73(62.9%)cases,including 21 cases of GJB2 gene mutation(8 cases 35delG,7 cases 176del16,4 cases 235delC,2 cases 299delAT),6 cases of GJB3 mutation(C358C>T),20 cases of SLC26A4 mutation(11 cases 2168 A>G,9 cases IVS7-2A>G),15 cases of mitochondrial 12S rRNA mutation(10 cases 1494C>T and 5 cases 1555A>G),7 cases with GJB2+SLC26A4 double mutation,and 4 cases with GJB3+mitochondrial 12S rRNA double mutation.Compared with those of the non-mutation group(n=43),the children in the gene mutation group had more severe hearing loss,and greater response thresholds at 0.5,1.0,2.0 and 4.0 kHz of Chirp-ABR and ASSR(P<0.05).In the gene mutation group,Chirp-ABR reaction threshold was related to that of ASSR at the 4 kinds of detecting frequencies(rS=0.517,0.608,0.515,0.651,P<0.001).There were no significant differences in the degree of hearing impairment,Chirp-ABR and ASSR response thresholds at the 4 kind of frequencies between single-site mutation and double-site mutation,or among the 4 deafness gene mutation groups(P>0.05).Conclusion:Children with congenital deafness have high mutation rate of the 4 deafness genes,mainly single point mutation.Children with mutations in deafness genes have increased hearing impairment.