语前聋儿童人工耳蜗植入后语音特征的分析及其同遗传相关性的研究
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摘要
耳聋是一种严重影响人类生活质量的常见疾病,目前已知重度及极重度耳聋中由遗传因素所致占60%。本实验在测试语前聋儿童人工耳蜗植入后元音、辅音声学参数以及汉语普通话音调特征变化的基础上,探讨分析这些声学特征的变化规律和趋势。同时对聋儿进行耳聋相关基因的筛查,并在耳蜗植入术中行NRT检测。之后将基因检测结果和NRT结果结合分析两者间的联系,从而验证遗传性耳聋患儿听神经通路及功能是否完整,并为阐述遗传因素在听觉及言语康复中的预测作用奠定基础。最后本实验对GJB2相关性耳聋患儿的语音声学参数做进一步分析,从而发现并探究GJB2基因在言语产生中的作用,为阐述遗传因素在语前聋儿童人工耳蜗植入后听觉及言语康复中的预测作用提供依据。
目的:
1、通过主观评价并利用语音分析软件对植入人工耳蜗的语前聋儿童的元音、辅音和汉语音调特征进行分析,探讨这些语音特征的变化特点及规律,从而为植入耳蜗的语前聋儿童言语可懂度的分析奠定基础,并为寻求一种新的更加客观的言语康复评估方式提供思路和依据。
2、对植入耳蜗的语前聋儿童进行耳聋相关基因的筛查,结合这些患儿术中神经反应遥测(NRT)的结果分析耳聋相关基因同听神经通路完整性之间的关系,从而为遗传因素对听神经功能及言语康复效果的预测性作用提供证据和支持。
3、对植入耳蜗的语前聋儿童进行GJB2基因的测序分析。同时对这些患儿的语音特征变化进行进一步研究。分析两者之间是否具有相关性,从而为验证遗传因素(GJB2突变)是否可以预测耳蜗植入后言语产生的康复效果提供依据,并为今后的进一步研究奠定基础。
方法:
1.(第一部分):语前聋儿童耳蜗植入后元音、辅音声学特征和声调特征的分析:按年龄和首次测试时耳蜗开机时间的不同分组,之后再间隔8～10个月,分别对上述儿童进行第二次录音测试。先对录音内容进行主观评价,之后利用praat语音分析软件对上述录音内容的声学参数进行分析。同时在各时间段分别将上述结果同正常对照进行比较分析。以了解各声学特征的变化情况。并将两种评测方法进行对照,以了解两者评估方法的差异。
2.(第二部分):利用基因芯片技术对植入耳蜗的语前聋儿童进行耳聋相关基因GJB2、GJB3、SLC26A4、线粒体DNA相关基因的已知突变位点进行筛查。同时对上述患儿在耳蜗植入术中进行神经反应遥测(NRT)的监测,分析两者之间是否存在联系。
3.(第三部分):对语前聋儿童进行GJB2基因的全序列测序分析。将受试儿童按GJB2突变与否分为:GJB2相关性耳聋和非GJB2相关性耳聋。对上述两组儿童的言语可懂度进一步研究,分析两者之间的相关性。
结果:
1.1、(第一部分):在言语可懂度方面,首次测试时开机时间小于一年的低龄儿童两次测试差异显著,第二次测试时言语可懂度结果也明显优于高龄组儿童第二次测试时结果。高龄组儿童在两次测试时结果也有显著性差异。对首次测试时开机时间大于一年的二组儿童进行上述评价分析:低龄组儿童两次测试结果间有显著性差异,但高龄组儿童两次测试间差异无显著性。两组儿童在音调产生方面同对照组间差异显著。在声学分析中:各元音共振峰同正常对照间的差异不完全一致,但显著性差异主要为受试儿童的第一共振峰明显高于对照组,而第二共振峰低于对照组。在辅音声学分析中,受试儿童的塞音、塞擦音、擦音以及浊擦音和鼻音同正常对照之间也有许多差异。主要表现为辅音VOT或辅音CD明显高于或低于对照组。对于声调的声学分析可以更直观的反应出各音调的变化趋势。
2.2、(第二部分):参与研究儿童的基因芯片筛查结果为:GJB2基因的杂合和纯合突变以及该基因的复合杂和突变。SLC26A4基因的IVS纯合突变以及GJB2和IVS的复合杂和突变。从受试儿童的NRT结果中可知,GJB2相关性耳聋的患儿NRT波形更加典型,而耳聋基因为野生型的儿童存在不典型的NRT结果。
3.3、(第三部分):对受试儿童进行GJB2基因的测序分析,除235delC,299——300delAT以及235delC和299delAT复合杂合突变等致病性突变外,未发现新的突变位点,以上筛查结果同其它文献报道中的基本一致。按GJB2突变与否分组后两组儿童言语可懂度结果有显著性差异,GJB2基因同耳蜗植入后言语产生有相关性。
结论:
1、低年龄植入儿童的言语产生效果好于高年龄组儿童,随耳蜗开机使用时间的延长,言语产生的语音参数逐渐趋于同正常对照组接近,在开机时间超过一年后受试儿童言语产生的进步程度减慢,在高龄组儿童中尤为明显。随着耳蜗的使用受试儿童可以利用耳蜗提供的听觉反馈矫正自己的发音方法,而声学分析可以更好的反应出受试儿童元音及辅音方法间的细致差别,因此可以更好的为发音矫正提供参考。而声调的声学分析较主观评价可以更直观,准确的反应出声调的变化及趋势。
2、JGB2基因突变是引起耳聋最主要的遗传因素,其突变率同其他学者报道的相近。通过对术中NRT的分析可知GJB2基因突变儿童的NRT波形较耳聋基因野生型儿童更加典型,但由于资料较少,目前尚未发现两者之间的相关性。遗传因素是预测听神经传导通路完整性的重要参考指标。通过术前的耳聋基因筛查可以为预后判断提供一定的帮助。
3、GJB2相关性耳聋患儿的言语产生优于非GJB2突变的耳聋儿童,GJB2突变同言语产生具有相关性,因此术前进行该基因的筛查不仅可以明确耳聋的遗传病因,并对言语产生的预后判断具有重要参考作用。
The deafness is a common disease critically to influence quality of life.Now about 60%of severe to profound hearing loss was caused by heredity.Basing on measurement of acoustic parameters of vowels,consonants and tone features of mandarin in prelingual deafness children with cochlear implant and to study the change in the law and tedency about these acoustic features.At the same time to screen deafness genes in these children and to do the NRT in operations.And then, combining the results of gene screening and NRT to analyse the correlations between them so to verify the function and integrity of auditory nerve pathway in heredity deafness.And to explain the prognostic effects of genetic factors in auditory and speech rehabilitation.In this studies,progressively to analyse the acoustic parameters of GJB2 hearing loss children so to reserch the contributions of GJB2 gene in speech production and to provide evidences of prognostic effects of gene in hearing and speech rehabilitation in prelingual deafness children with cochlear implant.
Objective:
1.To analyse features of vowels,consonants and tones in prelingual hearing loss children with cochlear implants by subjective way and software of phonetics.To discuss features and regulations of these phonemes so to establish the foundation of analysing intelligibility of speech in prelingual hearing loss children with cochlear implants and to provide ideas and evidences of newer and more objective methods of evaluating speech rehabilitation.
2.To screening genes of correlated hearing loss in prelingual deafness children.In operations,to do the NRT and then to combine the results of two parts to analyse the relation bewteen auditory nerve pathway and genes so to provide the evidences and supports of genetic predictable effects for auditory nerve function and rehabilitation efficacy of speech.
3.To do the sequencing analysis of JGB2 in these children at the same time progressively to analyse the variations of intelligibility of speech and the production results in children with cochlear implants.To establish the foundantion of future research.
Method:
1.(part 1):According to different ages and beginning employment time of cochlear implant to divide these children into subgroups.After 2～3moths and 8～10months to measure subjective and phoetic parameters after first mapping, respectively.Utilizing PRAAT software to analyse acoustic parameters at the same time to compare the results with controls so to learn about the variations of these parameters.Furthermore,to compare the results with subjective methods and learn about the difference between them..
2.(part 2):Utilizing the Gene Chip to screen the genes of GJB2,GJB3,SLC26A4 and Mitochondrial Gene(mtDNA) which are correlated with hereditory hearing loss.In implanting operations,to monitor the NRT for these children.And then to analyse the relation between them.
3.(part 3):Sequencing the complete sequence of GJB2 in prelingual deaf children. And then divide these children into three groups according to with GJB2 mutation and without it.Further studying the intelligibility of speech features about two groups so to analyse the correlation between them.
Results:
1.In speech intelligibility,the results were very different between two measurements in lower children and older children whose beginning time was lower one year. And the results of second time of lower age children were better than older ones. To analyse subjectively two groups:the lower age children had different results but older ones not.About tone,the results were different between groups and controls.About analysis of phonetic:the formant of vowels were different between deaf childern and controls.The difference were that the value of formants of deaf children were lower or higher than controls.But about consonants,there were very different in plosive,affricate,firctive and nasal between measured children and controls.The variable tendency of tone can be macroscopic reflected by phonetic analysis of tone.
2.The results of screen by Gene Chip in participated children were heterozygous, homozygous,compound heterozygous mutations in GJB2,IVS homozygous mutation in SLC26A4 and compound heterozygous in it.By the results of NRT,the waveforms of NRT with GJB2 were more typical and reproducibility by different intensions and better than non-GJB2 ones.
3.The results of sequences were not to find new mutational site execpt for 235delC, 299-300delAY and compound heterozygous mutation.These results were same as other literatures and the second part.There were significient difference about the results of intelligibility of speech in two groups,according to GJB2 mutating if or not.The speech production was correlated by the mutation of GJB2.
Conclusion:
1.The capability of speech production in lower age children were better than the older ones.Following temporal length of device turn-on,the parameters of speech production were gradually closing to normal control but the progress of tone features were not significance.When the time of utilization over one year the progress were slower this result were more obvious in old age.By using the devices,children can corrcet their manner of articulation.The analysis of phonetic can find the fine difference of vowels and consonants between these children and controls so can provide information for correcting articulation.The methods can reflect the variable tedency of tone more directly and precisely.
2.The mutation of GJB2 is the most supreme heredity cause.In this test,the mutation rate was the same as other literatures.The waves of NRT were better in children with the mutation of GJB2 than ones without GJB2 mutation.But due to the children were a few so we couldn't find the correlation result between them.But we believe the genetic factor can be used to prognose the integrity of auditory nerve pathway and the gene-screen before operation can provide the help for prognosis.
3.The results of speech production in children with GJB2 mutation were better than the ones with non-GJB2.They were negative correlation.So the gene-screen of GJB2 before operation were significant for prognosing the speech production.
目的:
1、通过主观评价并利用语音分析软件对植入人工耳蜗的语前聋儿童的元音、辅音和汉语音调特征进行分析,探讨这些语音特征的变化特点及规律,从而为植入耳蜗的语前聋儿童言语可懂度的分析奠定基础,并为寻求一种新的更加客观的言语康复评估方式提供思路和依据。
2、对植入耳蜗的语前聋儿童进行耳聋相关基因的筛查,结合这些患儿术中神经反应遥测(NRT)的结果分析耳聋相关基因同听神经通路完整性之间的关系,从而为遗传因素对听神经功能及言语康复效果的预测性作用提供证据和支持。
3、对植入耳蜗的语前聋儿童进行GJB2基因的测序分析。同时对这些患儿的语音特征变化进行进一步研究。分析两者之间是否具有相关性,从而为验证遗传因素(GJB2突变)是否可以预测耳蜗植入后言语产生的康复效果提供依据,并为今后的进一步研究奠定基础。
方法:
1.(第一部分):语前聋儿童耳蜗植入后元音、辅音声学特征和声调特征的分析:按年龄和首次测试时耳蜗开机时间的不同分组,之后再间隔8～10个月,分别对上述儿童进行第二次录音测试。先对录音内容进行主观评价,之后利用praat语音分析软件对上述录音内容的声学参数进行分析。同时在各时间段分别将上述结果同正常对照进行比较分析。以了解各声学特征的变化情况。并将两种评测方法进行对照,以了解两者评估方法的差异。
2.(第二部分):利用基因芯片技术对植入耳蜗的语前聋儿童进行耳聋相关基因GJB2、GJB3、SLC26A4、线粒体DNA相关基因的已知突变位点进行筛查。同时对上述患儿在耳蜗植入术中进行神经反应遥测(NRT)的监测,分析两者之间是否存在联系。
3.(第三部分):对语前聋儿童进行GJB2基因的全序列测序分析。将受试儿童按GJB2突变与否分为:GJB2相关性耳聋和非GJB2相关性耳聋。对上述两组儿童的言语可懂度进一步研究,分析两者之间的相关性。
结果:
1.1、(第一部分):在言语可懂度方面,首次测试时开机时间小于一年的低龄儿童两次测试差异显著,第二次测试时言语可懂度结果也明显优于高龄组儿童第二次测试时结果。高龄组儿童在两次测试时结果也有显著性差异。对首次测试时开机时间大于一年的二组儿童进行上述评价分析:低龄组儿童两次测试结果间有显著性差异,但高龄组儿童两次测试间差异无显著性。两组儿童在音调产生方面同对照组间差异显著。在声学分析中:各元音共振峰同正常对照间的差异不完全一致,但显著性差异主要为受试儿童的第一共振峰明显高于对照组,而第二共振峰低于对照组。在辅音声学分析中,受试儿童的塞音、塞擦音、擦音以及浊擦音和鼻音同正常对照之间也有许多差异。主要表现为辅音VOT或辅音CD明显高于或低于对照组。对于声调的声学分析可以更直观的反应出各音调的变化趋势。
2.2、(第二部分):参与研究儿童的基因芯片筛查结果为:GJB2基因的杂合和纯合突变以及该基因的复合杂和突变。SLC26A4基因的IVS纯合突变以及GJB2和IVS的复合杂和突变。从受试儿童的NRT结果中可知,GJB2相关性耳聋的患儿NRT波形更加典型,而耳聋基因为野生型的儿童存在不典型的NRT结果。
3.3、(第三部分):对受试儿童进行GJB2基因的测序分析,除235delC,299——300delAT以及235delC和299delAT复合杂合突变等致病性突变外,未发现新的突变位点,以上筛查结果同其它文献报道中的基本一致。按GJB2突变与否分组后两组儿童言语可懂度结果有显著性差异,GJB2基因同耳蜗植入后言语产生有相关性。
结论:
1、低年龄植入儿童的言语产生效果好于高年龄组儿童,随耳蜗开机使用时间的延长,言语产生的语音参数逐渐趋于同正常对照组接近,在开机时间超过一年后受试儿童言语产生的进步程度减慢,在高龄组儿童中尤为明显。随着耳蜗的使用受试儿童可以利用耳蜗提供的听觉反馈矫正自己的发音方法,而声学分析可以更好的反应出受试儿童元音及辅音方法间的细致差别,因此可以更好的为发音矫正提供参考。而声调的声学分析较主观评价可以更直观,准确的反应出声调的变化及趋势。
2、JGB2基因突变是引起耳聋最主要的遗传因素,其突变率同其他学者报道的相近。通过对术中NRT的分析可知GJB2基因突变儿童的NRT波形较耳聋基因野生型儿童更加典型,但由于资料较少,目前尚未发现两者之间的相关性。遗传因素是预测听神经传导通路完整性的重要参考指标。通过术前的耳聋基因筛查可以为预后判断提供一定的帮助。
3、GJB2相关性耳聋患儿的言语产生优于非GJB2突变的耳聋儿童,GJB2突变同言语产生具有相关性,因此术前进行该基因的筛查不仅可以明确耳聋的遗传病因,并对言语产生的预后判断具有重要参考作用。
The deafness is a common disease critically to influence quality of life.Now about 60%of severe to profound hearing loss was caused by heredity.Basing on measurement of acoustic parameters of vowels,consonants and tone features of mandarin in prelingual deafness children with cochlear implant and to study the change in the law and tedency about these acoustic features.At the same time to screen deafness genes in these children and to do the NRT in operations.And then, combining the results of gene screening and NRT to analyse the correlations between them so to verify the function and integrity of auditory nerve pathway in heredity deafness.And to explain the prognostic effects of genetic factors in auditory and speech rehabilitation.In this studies,progressively to analyse the acoustic parameters of GJB2 hearing loss children so to reserch the contributions of GJB2 gene in speech production and to provide evidences of prognostic effects of gene in hearing and speech rehabilitation in prelingual deafness children with cochlear implant.
Objective:
1.To analyse features of vowels,consonants and tones in prelingual hearing loss children with cochlear implants by subjective way and software of phonetics.To discuss features and regulations of these phonemes so to establish the foundation of analysing intelligibility of speech in prelingual hearing loss children with cochlear implants and to provide ideas and evidences of newer and more objective methods of evaluating speech rehabilitation.
2.To screening genes of correlated hearing loss in prelingual deafness children.In operations,to do the NRT and then to combine the results of two parts to analyse the relation bewteen auditory nerve pathway and genes so to provide the evidences and supports of genetic predictable effects for auditory nerve function and rehabilitation efficacy of speech.
3.To do the sequencing analysis of JGB2 in these children at the same time progressively to analyse the variations of intelligibility of speech and the production results in children with cochlear implants.To establish the foundantion of future research.
Method:
1.(part 1):According to different ages and beginning employment time of cochlear implant to divide these children into subgroups.After 2～3moths and 8～10months to measure subjective and phoetic parameters after first mapping, respectively.Utilizing PRAAT software to analyse acoustic parameters at the same time to compare the results with controls so to learn about the variations of these parameters.Furthermore,to compare the results with subjective methods and learn about the difference between them..
2.(part 2):Utilizing the Gene Chip to screen the genes of GJB2,GJB3,SLC26A4 and Mitochondrial Gene(mtDNA) which are correlated with hereditory hearing loss.In implanting operations,to monitor the NRT for these children.And then to analyse the relation between them.
3.(part 3):Sequencing the complete sequence of GJB2 in prelingual deaf children. And then divide these children into three groups according to with GJB2 mutation and without it.Further studying the intelligibility of speech features about two groups so to analyse the correlation between them.
Results:
1.In speech intelligibility,the results were very different between two measurements in lower children and older children whose beginning time was lower one year. And the results of second time of lower age children were better than older ones. To analyse subjectively two groups:the lower age children had different results but older ones not.About tone,the results were different between groups and controls.About analysis of phonetic:the formant of vowels were different between deaf childern and controls.The difference were that the value of formants of deaf children were lower or higher than controls.But about consonants,there were very different in plosive,affricate,firctive and nasal between measured children and controls.The variable tendency of tone can be macroscopic reflected by phonetic analysis of tone.
2.The results of screen by Gene Chip in participated children were heterozygous, homozygous,compound heterozygous mutations in GJB2,IVS homozygous mutation in SLC26A4 and compound heterozygous in it.By the results of NRT,the waveforms of NRT with GJB2 were more typical and reproducibility by different intensions and better than non-GJB2 ones.
3.The results of sequences were not to find new mutational site execpt for 235delC, 299-300delAY and compound heterozygous mutation.These results were same as other literatures and the second part.There were significient difference about the results of intelligibility of speech in two groups,according to GJB2 mutating if or not.The speech production was correlated by the mutation of GJB2.
Conclusion:
1.The capability of speech production in lower age children were better than the older ones.Following temporal length of device turn-on,the parameters of speech production were gradually closing to normal control but the progress of tone features were not significance.When the time of utilization over one year the progress were slower this result were more obvious in old age.By using the devices,children can corrcet their manner of articulation.The analysis of phonetic can find the fine difference of vowels and consonants between these children and controls so can provide information for correcting articulation.The methods can reflect the variable tedency of tone more directly and precisely.
2.The mutation of GJB2 is the most supreme heredity cause.In this test,the mutation rate was the same as other literatures.The waves of NRT were better in children with the mutation of GJB2 than ones without GJB2 mutation.But due to the children were a few so we couldn't find the correlation result between them.But we believe the genetic factor can be used to prognose the integrity of auditory nerve pathway and the gene-screen before operation can provide the help for prognosis.
3.The results of speech production in children with GJB2 mutation were better than the ones with non-GJB2.They were negative correlation.So the gene-screen of GJB2 before operation were significant for prognosing the speech production.
引文
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