發(fā)布時(shí)間：2018-07-20 21:08

【摘要】：正常聽(tīng)力是語(yǔ)言形成和發(fā)展的基礎(chǔ),聽(tīng)力言語(yǔ)障礙直接影響日常生活交流與學(xué)習(xí)。耳聾是人類最為困惱的疾病之一,2006年我國(guó)第二次全國(guó)殘疾人抽樣調(diào)查報(bào)告顯示:各類殘疾人數(shù)共計(jì)8296萬(wàn)人,其中聽(tīng)力殘疾2780萬(wàn)人,居于各類殘疾之首,且以每年2~3萬(wàn)新生聾兒的速度增長(zhǎng),致聾原因包括遺傳、藥物、噪音、外傷、老年性或多種因素結(jié)合所致。其中,基因突變作為聽(tīng)障兒童的主要致聾原因所占的比例高達(dá)50%-60%。在我國(guó),GJB2與SLC26A4突變相關(guān)耳聾在遺傳性聾中所占比例約為35.5%,是檢出率最高的兩大責(zé)任基因。二者因發(fā)病機(jī)制不同,其臨床表現(xiàn)可能存在差異。因此從發(fā)病年齡、聽(tīng)力損失程度、CT表現(xiàn)等方面研究伴有GJB2和SLC26A4基因突變的耳聾人群的臨床和影像學(xué)特征,對(duì)于幫助明確診斷和指導(dǎo)臨床干預(yù)措施具有重要意義。人工耳蝸植入(Cochlear implantation,CI)技術(shù)的出現(xiàn)為雙側(cè)極重度感音神經(jīng)性聾患者提供了回歸有聲世界的機(jī)會(huì)。CI植入技術(shù)的日臻完善,耳蝸植入術(shù)患者的例數(shù)逐年增加,CI人群在聽(tīng)覺(jué)感知、言語(yǔ)識(shí)別和語(yǔ)言產(chǎn)出等方面的能力不斷提升,然而,術(shù)后康復(fù)效果仍存在較大的個(gè)體差異。隨著基因檢測(cè)和診斷技術(shù)的廣泛應(yīng)用,伴有基因突變的耳聾患兒已占據(jù)了CI人群的一大部分,不同的基因突變作為感音神經(jīng)性聾的致病原因?qū)I術(shù)后的聽(tīng)覺(jué)言語(yǔ)康復(fù)效果是否有影響,目前研究結(jié)果存在矛盾。不同地域和非英語(yǔ)語(yǔ)系耳聾基因相關(guān)感音神經(jīng)性聾CI術(shù)后聽(tīng)覺(jué)言語(yǔ)康復(fù)效果的研究資料尚少。本研究目的:1.觀察對(duì)比GJB2、SLC26A4基因突變相關(guān)感音神經(jīng)性聾患兒的發(fā)病年齡、聽(tīng)力損失程度及內(nèi)耳影像學(xué)特點(diǎn)。2.研究探討GJB2、SLC26A4基因突變相關(guān)感音神經(jīng)性耳聾患兒人工耳蝸植入術(shù)后聽(tīng)覺(jué)言語(yǔ)的康復(fù)特點(diǎn)。第一部分常見(jiàn)基因相關(guān)耳聾的臨床特點(diǎn)目的觀察對(duì)比GJB2、SLC26A4基因突變相關(guān)感音神經(jīng)性聾患兒的發(fā)病年齡、聽(tīng)力損失程度及內(nèi)耳影像學(xué)特點(diǎn)。方法研究對(duì)象為我院耳科門診就診經(jīng)耳聾基因芯片與DNA測(cè)序相結(jié)合的方法檢測(cè)結(jié)果為GJB2、SLC26A4基因純合或復(fù)合雜合突變的0~12歲感音神經(jīng)性聾患兒218例,其中GJB2基因純合或復(fù)合雜合突變患者123例,SLC26A4基因純合或復(fù)合雜合突變患者95例。按發(fā)病年齡分為嬰兒期組(0~1歲)、幼兒期組(1.1~3歲)、學(xué)齡前期組(3.1~6歲)及學(xué)齡期組(6.1~12歲),探討GJB2、SLC26A4基因純合或復(fù)合雜合突變患兒的發(fā)病年齡構(gòu)成、聽(tīng)力損失程度及顳骨CT影像學(xué)特點(diǎn)。結(jié)果1、GJB2、SLC26A4兩基因突變組患兒發(fā)病年齡在嬰兒期、幼兒期、學(xué)齡前期、學(xué)齡期的構(gòu)成比分別為:43.09%、37.40%、14.63%、4.88%與24.2%、44.21%、18.95%、12.63%,兩組發(fā)病年齡構(gòu)成差異有統(tǒng)計(jì)學(xué)意義(P=0.014)。2、GJB2、SLC26A4基因突變組患兒聽(tīng)力損失程度為中度、重度、極重度的構(gòu)成比分別為:8.94%、17.89%、73.17%及9.47%、34.74%、55.79%,GJB2組主要為極重度聽(tīng)力損失,與SLC26A4組聽(tīng)力損失程度構(gòu)成比差異有統(tǒng)計(jì)學(xué)意義(P=0.014)。3、GJB2基因突變患兒各年齡組間聽(tīng)力損失構(gòu)成比差異有統(tǒng)計(jì)學(xué)意義(P=0.000),再行兩兩組間比較示嬰、幼兒期組聽(tīng)力損失程度以極重度為主,發(fā)病年齡越小,極重度聽(tīng)力損失的比例越高,學(xué)齡前和學(xué)齡期組極重度聽(tīng)力損失的比例有所降低。SLC26A4基因突變患兒各年齡組聽(tīng)力損失程度均以重度、極重度為主,聽(tīng)力損失構(gòu)成比差異無(wú)統(tǒng)計(jì)學(xué)意義(P=0.686)。4、GJB2基因突變組99.19%(122/123)患兒內(nèi)耳結(jié)構(gòu)正常,僅一例CT顯示雙側(cè)內(nèi)聽(tīng)道狹窄,SLC26A4基因突變組95.79%(91/95)患兒顳骨CT結(jié)果伴有前庭水管擴(kuò)大。小結(jié)1、伴GJB2基因突變的耳聾患兒發(fā)病年齡集中在嬰、幼兒期(0~3歲),以極重度感音神經(jīng)性聾為主,多不伴內(nèi)耳畸形。2、SLC26A4基因突變感音神經(jīng)性聾患兒發(fā)病年齡多見(jiàn)于幼兒期(1.1~3歲),以重度、極重度感音神經(jīng)性耳聾為主,與伴前庭水管擴(kuò)大的內(nèi)耳畸形密切相關(guān)。第二部分常見(jiàn)基因相關(guān)耳聾人工耳蝸植入術(shù)效果分析目的研究探討GJB2、SLC26A4基因突變相關(guān)感音神經(jīng)性耳聾患兒人工耳蝸植入術(shù)后聽(tīng)覺(jué)言語(yǔ)的康復(fù)特點(diǎn)。方法觀察評(píng)估2015年1月-2016年2月在我科行單側(cè)CI植入術(shù)的患兒198例,男102例,女96例,植入年齡10月~6歲,平均3.14歲。根據(jù)基因檢測(cè)結(jié)果,分為GJB2組、SLC26A4組及未發(fā)現(xiàn)基因突變的為對(duì)照組。分別于術(shù)前,術(shù)后3月、6月、12月評(píng)估并比較三組患兒的聽(tīng)覺(jué)言語(yǔ)能力。評(píng)估內(nèi)容包括:聲場(chǎng)助聽(tīng)聽(tīng)閾測(cè)試、聽(tīng)覺(jué)行為分級(jí)(Categories ofauditory performance,CAP)和言語(yǔ)可懂度分級(jí)(Speech Intelligibility Rate,SIR)評(píng)分、言語(yǔ)識(shí)別能力測(cè)試采用《聽(tīng)障兒童聽(tīng)覺(jué)、語(yǔ)言能力評(píng)估標(biāo)準(zhǔn)》。結(jié)果1、GJB2組、SLC26A4組和對(duì)照組聽(tīng)覺(jué)言語(yǔ)能力均隨康復(fù)時(shí)間的延長(zhǎng)逐步提高,各組CAP、SIR評(píng)分及言語(yǔ)識(shí)別率和語(yǔ)言年齡在相鄰時(shí)間點(diǎn)的差異均有統(tǒng)計(jì)學(xué)意義(P0.05)。2、GJB2組各時(shí)間點(diǎn)CAP、SIR評(píng)分及言語(yǔ)識(shí)別率和語(yǔ)言年齡與對(duì)照組同一隨訪時(shí)間的結(jié)果相比差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。3、SLC26A4組術(shù)前、術(shù)后3月、術(shù)后6月CAP、SIR評(píng)分及言語(yǔ)識(shí)別率明顯高于GJB2組和對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。術(shù)后12月時(shí)的CAP、SIR評(píng)分及言語(yǔ)識(shí)別率與GJB2組和對(duì)照組的差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。SLC26A4組語(yǔ)言年齡在各時(shí)間點(diǎn)與其余兩組差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。小結(jié)1、SLC26A4基因突變SNHL患兒人工耳蝸植入后短期內(nèi)康復(fù)效果明顯優(yōu)于伴GJB2基因突變者和未檢出基因突變者。2、GJB2基因突變SNHL患兒術(shù)后能獲得較好的聽(tīng)覺(jué)言語(yǔ)康復(fù)效果,與未檢出基因突變者相當(dāng)。全文結(jié)論1.伴GJB2基因突變的耳聾患兒發(fā)病年齡集中在嬰、幼兒期(0~3歲),以極重度感音神經(jīng)性聾為主,多不伴內(nèi)耳畸形。2.SLC26A4基因突變感音神經(jīng)性聾患兒發(fā)病年齡多見(jiàn)于幼兒期(1.1~3歲),以重度、極重度感音神經(jīng)性耳聾為主,與伴前庭水管擴(kuò)大的內(nèi)耳畸形密切相關(guān)。3.SLC26A4基因突變感音神經(jīng)性聾患兒人工耳蝸植入后短期內(nèi)康復(fù)效果明顯優(yōu)于伴GJB2基因突變者和未檢出基因突變者。4.GJB2基因突變感音神經(jīng)性聾患兒術(shù)后能獲得較好的聽(tīng)覺(jué)言語(yǔ)康復(fù)效果,與未檢出基因突變者相當(dāng)。
[Abstract]:Normal hearing is the basis of language formation and development, hearing speech disorder directly affects daily life communication and learning. Deafness is one of the most distressed diseases of human being. In 2006, the second national sampling survey on disabled persons in China showed that the total number of disabled persons of all types was 82 million 960 thousand, and the hearing disability was 27 million 800 thousand, the first of all kinds of disabilities. The causes of deafness include heredity, drugs, noise, trauma, and combination of many factors. Among them, the proportion of the gene mutation as the main deafness cause of the hearing impaired children is up to 50%-60%. in China, and the proportion of the deafness associated with GJB2 and SLC26A4 mutation is about 35.5% in the hereditary deafness. It is the two major responsible gene for the highest detection rate. The clinical and the clinical and imaging features of the deafness people with GJB2 and SLC26A4 mutations are studied from the age, the degree of hearing loss, and the CT expression, so that the diagnosis and guidance of clinical intervention can be made to help clearly diagnose and guide the clinical intervention. Significance. The emergence of Cochlear implantation (CI) technology provides a chance for bilateral extremely severe sensorineural deafness to provide a chance to return to the world of sound..CI implantation is becoming more and more perfect. The number of cases of cochlear implantation is increasing year by year, and the ability of CI people to be aware of hearing, speech recognition, and language output constantly. However, there are still large individual differences in the effect of postoperative rehabilitation. With the extensive use of gene detection and diagnostic techniques, a large number of deafness children with genetic mutations have occupied a large part of the CI population. Different gene mutations have been used as the cause of the cause of sensorineural hearing loss on the effect of auditory speech rehabilitation after CI. There are some contradictions in the previous study. There are few research data on auditory speech rehabilitation effect after CI operation in different regional and non English language families with hearing loss gene related sensorineural hearing loss. 1. the purpose of this study was to compare the age of onset of GJB2, SLC26A4 gene mutation related sensorineural hearing loss in children, the degree of hearing loss and the.2. study of inner ear imaging. To explore the rehabilitation characteristics of auditory speech after cochlear implantation in children with GJB2, SLC26A4 gene mutation related to sensorineural deafness. The first part is to compare the clinical characteristics of the common gene related deafness and to compare the age of onset, the degree of hearing loss and the inner ear imaging characteristics of GJB2, SLC26A4 mutation related sensorineural hearing loss. Methods 218 children with GJB2, SLC26A4 homozygous or complex heterozygous mutations were detected in 218 children with 0~12 year old sensorineural deafness, including 123 cases of GJB2 homozygous or complex heterozygous mutations, and SLC26A4 homozygous or compound heterozygous mutations in the 218 cases of GJB2, homozygous or complex heterozygous mutation in our hospital. 95 cases were divided into infant group (0~1 years old), early childhood group (1.1~3 years), pre school age group (3.1~6 years old) and school age group (6.1~12 years old). The age constitution of children with GJB2, SLC26A4 gene homozygous or complex heterozygous mutations, hearing loss and temporal bone CT imaging characteristics were investigated. The results of the 1, GJB2, SLC26A4 two gene mutation group were found. The proportion of age in infancy, infancy, pre school age and school age were 43.09%, 37.40%, 14.63%, 4.88% and 24.2%, 44.21%, 18.95%, 12.63%, and two groups were statistically significant (P=0.014).2, GJB2, and SLC26A4 gene mutation group was moderate, severe and extremely severe: 8.94%, 17.89, respectively. %, 73.17% and 9.47%, 34.74%, 55.79%, group GJB2 was the most severe hearing loss, and the ratio of hearing loss in the SLC26A4 group was statistically significant (P=0.014).3. The ratio of hearing loss in children with GJB2 gene mutation was statistically significant (P=0.000), and then the 22 groups were compared and the degree of hearing loss in the early childhood group The proportion of extreme severe hearing loss was higher, the proportion of extreme severe hearing loss in preschool and school age groups decreased with severe severe hearing loss. The degree of hearing loss in all age groups of.SLC26A4 gene mutation was severe, most severe, and the ratio of hearing loss was not statistically significant (P=0.686).4, GJB2 gene mutation. In group 99.19% (122/123), the inner ear structure of children was normal, only one case with CT showed bilateral internal auditory stenosis, and the SLC26A4 gene mutation group 95.79% (91/95) had CT in the temporal bone with enlargement of the vestibular aqueduct. 1, the age of children with deafness with GJB2 gene mutation was concentrated in infant, early childhood (0~3 years), most severe sensorineural deafness and no inner ear. The age of.2, SLC26A4 gene mutation and sensorineural hearing loss in children is mostly in early childhood (1.1~3 years), mainly with severe, extremely severe sensorineural deafness, closely related to the internal ear malformation with enlarged vestibule pipes. The second part of the common gene related deafness cochlear implantation is to study the GJB2, SLC26A4 gene The characteristics of auditory speech rehabilitation after cochlear implantation in children with mutational related sensorineural deafness were observed. Methods a total of 198 children, 102 males and 96 females, aged 3.14 years old in October -2016 years in February January 2015, were observed and assessed. The results were divided into group GJB2, SLC26A4 group and unfound basis according to the results of gene detection. The auditory speech ability of the three groups was evaluated and compared before the operation, in March, in June, and in December, respectively. The evaluation contents included sound field hearing hearing threshold test, Categories ofauditory performance, CAP, Speech Intelligibility Rate, SIR score, and speech recognition ability test. The hearing of the hearing impaired children, the standard of language ability evaluation was more than. Results 1, the auditory speech ability of group GJB2, SLC26A4 group and control group increased gradually with the prolongation of recovery time. The difference of CAP, SIR score, speech recognition rate and language age at adjacent time points were statistically significant (P0.05).2, GJB2 group time point CAP, SIR score and speech in each group. There was no significant difference in speech recognition rate and language age compared with the results of the same follow-up time in the control group (P0.05).3. Before operation, March, and CAP after operation in group SLC26A4, SIR score and speech recognition rate were significantly higher than that of group GJB2 and control group, the difference was statistically significant (P0.05). The CAP, SIR score, speech recognition rate and GJB2 group in December after operation. There was no significant difference in the difference between the control group and the control group (P0.05) the language age of the group.SLC26A4 was not statistically significant (P0.05) at all time points and the other two groups. The conclusion was 1. The short-term rehabilitation effect of the cochlear implant in children with SLC26A4 gene mutation was better than that of the GJB2 gene mutation and the undetected gene mutation,.2, and the GJB2 gene mutation in SNHL patients. Conclusion 1. children with deafness with GJB2 gene mutation are concentrated in infants, early childhood (0~3 years), most severe sensorineural deafness, and children with more non.2.SLC26A4 gene mutations and sensorineural hearing loss are more common in children. In early childhood (1.1~3 years of age), severe, extremely severe sensorineural deafness is the main factor, and the.3.SLC26A4 gene mutation is closely related to the enlarged inner ear malformation associated with the vestibule tube. The short-term rehabilitation effect of the cochlear implantation in children with sensorineural deafness is obviously better than that of the GJB2 gene mutation and the.4.GJB2 mutation in the undetected gene mutants. Children with deafness can achieve better hearing and speech rehabilitation after operation, and are equal to those without gene mutation.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R764.43

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