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目的:分析陕西省非综合征型耳聋患者GJB2基因的突变类型及突变频率。方法采集陕西省800例散发非综合征型耳聋患者和104例听力正常者外周血,提取基因组DNA,采用聚合酶链反应扩增GJB2基因全部编码区并进行测序,序列与GJB2基因标准序列进行比对分析。结果共检出29种突变类型,包括5种多态性改变、19种病理性突变以及5种未见报道的突变类型。耳聋患者与对照组间235delC和299_300delAT的检出率差异具有统计学意义。153例患者由于携带GJB2基因纯合/复合杂合突变致聋。结论 GJB2基因235delC、299_300delAT以及176_191del16为陕西省非综合征型耳聋患者最常见的三种突变类型。 相似文献
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江苏南通地区非综合征性耳聋GJB2基因突变分析 总被引:2,自引:1,他引:2
目的 研究南通地区非综合征性耳聋GJB2基因突变情况。方法 收集南通地区海安县和如皋县聋哑学校学生100名和健康对照组50名,利用PCR扩增及限制性内切酶酶切分析初筛GJB2 235delC突变者,然后再行DNA直接测序。结果 耳聋组中共发现三种突变:235delC、176—191del16、299—300delAT。235delC是主要突变方式.约30%的患者携带此突变;299—300delAT和176-191del16突变检出率分别为9%和8%。对照组未发现这些突变。结论 南通地区非综合征性耳聋GJB2基因突变率较高,因此在南通地区进行广泛的生育前耳聋基因筛查工作有重要意义。 相似文献
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目的研究广东、湖南和广西三省非综合征型聋患者GJB3和GJB6基因突变的特征。方法选择200例来自广东、湖南和广西三省的非综合征型聋患者,提取外周血DNA,PCR扩增后,进行GJB3、GJB6基因编码区测序和GJB6大片段缺失del(GJB6-D13S1830)及del(GJB6-D13S1854)突变检测。结果 200例患者中发现GJB3 580G>A杂合突变2例,其中1例为GJB2 109G>A和GJB3 580G>A复合杂合突变,250G>A杂合突变1例,474G>A杂合突变1例,357C>T杂合突变35例,纯合突变1例,474G>A为首次发现。GJB3等位基因突变频率为1%(4/400)。未发现GJB6基因突变。结论本组广东、湖南和广西三省非综合征型聋患者GJB3基因等位基因突变率为1%;GJB6基因突变致聋罕见。 相似文献
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目的检测GJB2单杂合突变非综合征型耳聋患者GJB2全序列中是否有大片段的碱基插入或缺失,研究GJB2全序列长链PCR方法和电泳方法。方法应用长链PCR方法对201例GJB2单杂合突变非综合征型耳聋患者进行GJB2全序列长度检测,对照组为111例听力正常的成年人。应用两步法PCR,调整加入DNA模板量、PCR延伸时间、循环次数等,0.8%琼脂糖凝胶电泳检测PCR产物的长度和量,调整加样槽的宽度、加样量、电泳电压、电流、电泳时间得到清晰条带,若PCR产物存在大片段碱基插入或缺失,用限制性内切酶BamHI进行内切酶反应,初步判断插入或缺失的大致位置。结果 201例GJB2单杂合突变患者中,GJB2序列长度未见大片段碱基插入或缺失。对照组GJB2序列长度未见异常。结论 GJB2单杂合突变非综合征型耳聋患者中GJB2序列长度检测未见明显异常。 相似文献
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目的应用耳聋基因芯片对先天性非综合征型感音神经性聋患儿及有明确遗传史病例的家族成员进行常见耳聋相关基因检测,分析不同的可能已知相关因素引起的先天性聋患儿基因突变的热点位点,探讨突变基因位点与耳聋病因的相关性,并对热点突变基因的家系遗传规律进行初步分析。方法先天性非综合征型感音神经性聋儿童109例,通过CT检查及问卷调查寻找其可能的发病原因。对所有病例均采集血液样本,提取DNA,并以26例健康儿童作为对照组,应用耳聋基因芯片进行常见耳聋相关基因检测,分析突变位点及突变频率与耳聋病因的相关性。同时,对有明确遗传史的5个家族的相关成员进行相应检测,并绘制家系图,对热点突变基因可能的遗传方式进行初步探讨。结果 109例耳聋儿童的外周血样本中,GJB2和SLC26A4基因突变均有较高的检出率,所有病例均未检测到GJB3基因突变。线粒体均质突变检出3例,均有明确的氨基甙类抗生素用药史;实验组基因突变检出率明显高于对照组(P<0.001),有明确遗传病史组突变检出率明显高于无遗传病史组(P<0.001),有前庭导水管扩大组突变检出率明显高于无前庭导水管扩大组(P<0.001);SLC26A4基因突变主要集中于SLC26A42168A>G和SLC26A4IVS7-2A>G位点,与有无遗传病史和有无前庭导水管扩大均有显著相关性(P<0.01),GJB2基因突变主要集中于GJB2235delC和GJB2299delAT位点,本组病例显示其突变率与有无遗传病史无显著相关性(P>0.05);对4个大前庭导水管综合征家系和1个遗传性耳聋家系的分析显示,5个家系的遗传方式均符合常染色体隐性遗传规律。结论先天性非综合征型耳聋患者耳聋相关基因突变率明显高于正常人群,GJB2、SLC26A4基因突变均有较高检出率。本组病例显示GJB2基因突变与家族遗传史无明显相关性,而SLC26A4基因主要在大前庭导水管综合征患者中被检出,并表现出明显的家族遗传性,其遗传方式符合常染色体隐性遗传规律;线粒体均质突变多集中于12SrRNA1555A>G位点,主要在药物中毒性耳聋患儿中被检出。 相似文献
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目的利用JL055小家系分析GJB2基因突变导致非综合征性耳聋(non-syndromic hearing impairment,NSHI)的特点,为遗传咨询和产前诊断提供理论基础。方法对来自吉林聋哑学校的先证者JL055及其部分家属的血样,进行GJB2基因聚合酶链反应(polymerase chain reaction,PCR)扩增产物测序,检测GJB2基因的序列改变,对测序结果进行临床分析。结果JL055的基因型为35delG/299-300delAT,两个等位基因分别来自父系和母系。结论JL055家系的测序结果为遗传咨询和产前诊断提供了理论基础。 相似文献
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目的:研究新疆哈萨克族非综合征型聋患者GJB2基因突变的情况。方法:调查对象为来自新疆地区的193例哈萨克族患者,采用直接测序法对非综合征型聋患者97例和健康对照96例进行GJB2基因突变的检测。结果:在编码区耳聋组共发现8种碱基改变:其中35delG纯和12例,79G〉A纯合5例,79G〉A杂合8例,79G〉A与608T〉C复合杂合1例,79G〉A与341A〉G复合杂合5例,235delC杂合4例,341A〉G杂合2例,439T〉G杂合1例,457G〉A杂合1例,521G〉A纯合2例。对照组发现4种已明确的常见多态性碱基改变。结论:本研究提示新疆哈萨克族非综合征型聋患者GJB2基因突变具有种族和地域性特点,该地区哈萨克族耳聋人群中GJB2有较高携带率,在本研究中35 delG为其常见突变方式。 相似文献
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目的分析重度和极重度非综合征型聋患者常见耳聋基因突变情况,从分子水平了解该人群聋病的遗传病因和特点,为临床防聋治聋提供策略、依据。方法应用遗传性耳聋基因芯片对179例非综合征型聋患者GJB2、GJB3、SLC26A4、线粒体12SrRNA基因中9个热点突变进行检测,同时结合耳聋病因问卷调查、纯音听阈测试、听性脑干反应测试、声导抗、颞骨CT检查。结果 179例患者中,79例存在不同程度的被检测基因位点突变,其中3例同时携带二个基因突变:①42例存在GJB2基因突变,其中:176del16位点纯合突变1例、单杂合突变2例;235delC位点纯合突变17例、单杂合突变9例;299delAT位点纯合突变0例、单杂合突变2例;235delC/299delAT复合杂合突变7例,235delC/176del16复合杂合突变4例。②37例存在SLC26A4基因突变,其中:2168A>G位点单杂合突变4例;IVS7-2A>G位点纯合突变13例,单杂合突变17例;2168A>G/IVS7-2A>G复合杂合突变3例。③3例存在线粒体12SrRNA基因突变,其中2例1555A>G位点均质突变,1例1494C>T位点均质突变;④无GJB3基因突变。在基因水平,明确诊断遗传性聋者48例,占26.80%,遗传性耳聋基因突变携带者31例,占17.32%。结论 GJB2、SLC26A4突变是安徽地区重度和极重度非综合征型聋患者主要突变形式、其次是线粒体12SrRNA基因突变,通过筛查可以明确部分非综合征型聋的病因,可以为患者及其家族成员提供准确的遗传咨询和指导,为再次生育家庭提供产前诊断,从而为防聋治聋提供帮助。 相似文献
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产前诊断对遗传性耳聋家庭的生育指导 总被引:2,自引:0,他引:2
目的通过一典型的有再生育要求的耳聋家庭病例,具体阐述耳聋产前诊断为耳聋家庭提供科学生育指导的内容、过程及意义。方法此耳聋家庭育有一子,为先天性耳聋患者,父母均为昕力正常者。对先证者进行详细的体格检查、昕力学及影像学检查后,采集先证者及其父母的外周血并提取DNA,进行GJB2,SLC26A4(PDS)基因分析和线粒体DNA(mtDNA)A1555G位点突变检测。明确受检者基因型并向该家庭提供遗传学信息后,在母亲妊娠早期(约10周)行产前诊断取材并提取DNA,明确胎儿的基因型。结果先证者携带GJB2复合突变,父母为携带者,此耳聋家庭再发风险为25%,产前诊断显示胎儿仅携带一个母系突变,出生后随访听力正常。结论耳聋产前诊断可为遗传性耳聋家庭提供科学的生育指导。 相似文献
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目的:在DNA水平上对一个非综合征型耳聋家系进行耳聋易感基因的突变筛查,确定家系成员的致病基因及分型。方法:收集家系成员外周血,提取DNA进行等位基因多重PCR,基因芯片杂交筛查GJB2、GJB3、PDS和mtDNA 12SRNA基因突变,DNA测序验证基因芯片结果。结果:先证者为GJB2基因235delC和299-300delAT复合杂合,其父母分别为GJB2基因235delC和299-300delAT纯合突变基因型,父系亲属中耳聋者均为299-300delAT纯合突变基因型,听力正常成员为杂合基因型,该致病基因来源于近亲婚配祖父母。结论:GJB2基因突变是导致该家系发生耳聋的致病因素,耳聋基因芯片检测是确定遗传性聋病因的必要手段。 相似文献
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Siqing Fu Chunfang Wang 《International journal of pediatric otorhinolaryngology》2010,74(10):1122-1125
Objective
Recent advances in molecular biology of hearing and deafness have made genetic testing an option for deaf individuals and their families. In China, DNA microarray and other genetic testing method has been applied to rapid genetic diagnosis of non-syndromic hearing loss. However, there is no information about the interests in such testing in China. The purpose of this study is to document the attitudes of parents with normal hearing who have one or more deaf children toward diagnostic, carrier, and prenatal genetic testing for deafness.Methods
A structured, self-completion questionnaire was given to delegates at a conference held at Hubei Rehabilitation Research Center for Deaf Children, Wuhan, China on March 3, 2010. Of 366 surveys distributed, 290 were completed and returned.Results
Ninety-four percent of the respondents had a positive attitude toward genetic testing. Seventy-two percent stated that they were interested in genetic testing of deaf child. Of the individuals who were interested in such testing, 69% would consider having prenatal genetic testing for deafness.Conclusion
The present study provided evidence of a predominantly positive attitude toward genetics. Appropriate genetic counseling can help parents to understand the risk, benefits, and limitations of genetic testing for prelingual deafness. 相似文献14.
Richard J. Vivero 《International journal of pediatric otorhinolaryngology》2010,74(10):1107-1112
Genetic factors are among the main etiologies of severe to profound hearing loss and may play an important role in cochlear implantation (CI) outcomes. While genes for common forms of deafness have been cloned, efforts to correlate the functional outcome of CIs with a genetic form of deafness carried by the patient have been largely anecdotal to date. It has been suggested that the differences in auditory performance may be explained by differences in the number of surviving spiral ganglion cells, etiology of hearing loss, and other factors. Knowledge of the specific loci and mutations involved in patients who receive cochlear implants may elucidate other factors related to CI performance. In this review article, current knowledge of cochlear implants for hereditary hearing loss will be discussed with an emphasis on relevant clinical genotype-phenotype correlations. 相似文献
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目的:利用基因诊断的方法调查内蒙古自治区赤峰市特教学校非综合征耳聋患者的常见分子病因,对GJB2、GJB3、GJB6基因编码区突变进行分析.方法:调查对象来自赤峰市特教学校非综合征耳聋患者134例(耳聋组),对照组为中国北方地区(北京、河北、内蒙、山西)听力正常者100例.所有受检者均采集外周血并提取DNA,首先进行GJB2基因编码区测序,对携带GJB2单杂合突变的患者进一步检查GJB6 del(GJB6-D13S1830)突变并进行GJB6编码区测序.对除GJB2基因、线粒体A1555G突变相关性耳聋及前庭水管扩大综合征外的分子病因不明的91例非综合征耳聋患者进行GJB3基因编码区测序.结果:134例非综合征耳聋患者及100例正常对照中共检测到6种GJB2基因新的突变方式.耳聋组41例携带GJB2病理性突变,其中双等位基因突变22例,单等位基因突变19例,在GJB2单等位基因突变的耳聋患者中未检测到GJB6 del(GJB6-D13S1830)及编码区其他突变;对照组4例携带GJB2基因病理性突变.在91例分子病因不明的耳聋患者及100例正常对照中共检测到3种GJB3基因新的突变方式.耳聋组2例携带GJB3基因病理性突变,均为杂合子,其中1例同时携带GJB2单等位基因突变235delC;对照组1例携带GJB3基因病理性突变.结论:通过GJB2、GJB6、GJB3基因编码区突变分析为赤峰市特教学校16.42%(22/134)的非综合征耳聋学生明确了分子病因;新发现的突变和多态丰富了中国人GJB2、GJB3基因突变及多态性图谱,为深入开展耳聋基因筛查奠定了基础. 相似文献
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目的:检测耳聋家系中耳聋患者的基因型,结合听力损失程度,分析常见耳聋基因的基因型与表型之间的关系。方法:选取2个耳聋小家系,检测4个耳聋基因的9个位点的突变,同时对家系成员进行纯音测听检查。结果:LGR-1家系中,Ⅰ:1、Ⅰ:2、Ⅰ:4和Ⅱ:5基因型为单杂合突变,表型为轻中度聋;Ⅱ:3和Ⅱ:4基因型为双杂合突变,Ⅱ:2和Ⅲ:1基因型为复合杂合突变,表型均为重度或极重度聋。HXL-2家系中,Ⅰ:1和Ⅰ:2基因型为单杂合突变,表型为轻中度聋;Ⅱ:2、Ⅱ:3、Ⅱ:5和Ⅲ:2基因型为单杂合突变,但表型为重度或极重度聋;Ⅱ:1基因型为双杂合突变,表型为极重度聋;Ⅲ:1基因型为单杂合突变,左耳为中度聋,右耳为中重度聋。结论:单杂合突变患者表型多为轻度或中度聋,而基因型为单杂合突变的重度或极重度聋患者可能存在另外一个没有检测到的突变;基因型为双杂合突变或复合杂合突变的患者,表型多为重度或极重度聋;基因型与听力表型之间存在一定的正相关性。 相似文献
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Autosomal recessive and sporadic deafness in Morocco: high frequency of the 35delG GJB2 mutation and absence of the 342-kb GJB6 variant 总被引:1,自引:0,他引:1
Deafness is a heterogeneous disorder showing different pattern of inheritance and involving a multitude of different genes. Mutations in the gene, GJB2 Gap junction type 1), encoding the gap junction protein connexin-26 on chromosome 13q11 may be responsible for up 50% of autosomal recessive nonsyndromic hearing loss cases (ARNSHL), and for 15–30% of sporadic cases. However, a large proportion (10–42%) of patients with GJB2 has only one GJB2 mutant allele. Recent reports have suggested that a 342-kb deletion truncating the GJB6 gene (encoding connexin-30), was associated with ARNSHL through either homozygous deletion of Cx30, or digenic inheritance of a Cx30 deletion and a Cx26 mutation in trans. Because mutations in Connexin-26 (Cx26) play an important role in ARNSHL and that distribution pattern of GJB2 variants differs considerably among ethnic groups, our objective was to find out the significance of Cx26 mutations in Moroccan families who had hereditary and sporadic deafness. One hundred and sixteen families with congenital deafness (including 38 multiplex families, and 78 families with sporadic cases) were included. Results show that the prevalence of the 35delG mutation is 31.58% in the family cases and 20.51% in the sporadic cases. Further screening for other GJB2 variants demonstrated the absence of other mutations; none of these families had mutations in exon 1 of GJB2 or the 342-kb deletion of GJB6. Thus, screening of the 35delG in the GJB2 gene should facilitate routinely used diagnostic for genetic counselling in Morocco. 相似文献
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目的构建人野生型CX30红色荧光表达载体,将Cx26野生型和突变型分别与CX30共同转染HEK293细胞,为揭示Cx26--235delC的杂合突变患者的发病机制提供实验依据。方法构建pCx30--IREs2-DsRed—Express真核表达载体,将pcx30—IREs2-DsRed—ExPress分别与pCx26--EGFP或pCx26--235deIC--EGFP以1:1的比例用脂质体法转染HEK293细胞,转染48h后在激光共聚焦显微镜下观察结果,计算同时表达红色和绿色的细胞阳性率,卡方检验比较两组阳性率的差异。结果pCx30--IRES2--DsRed--Express与pCx26--EGFP共同转染HEK293细胞后,同时出现红色和绿色荧光的细胞占全部转染阳性细胞的27.32%(91/333)。pCx30—IRES2--DsRed--Express与pCx26--c235deIC--EGFP共同转染HEK293细胞后,同时表达红色与绿色信号的细胞占全部阳性细胞的2.19%(4/183),明显低于两种野生型质粒共同转染的阳性率,经卡方检验两者差异具有显著性意义(x2=52.89,P〈0.01)。结论Cx26发生C.235deIC突变后,丧失了与野生型Cx30形成异型性缝隙连掇gapjunctions,GJs)的能力,使异型性GJs的总数显著下降,导致耳蜗失去了重要的细胞间联系通道,推测可能与部分c.235delC杂合子耳聋的发生有关。 相似文献
19.
Joana Rita Gaspar de Barros Martinho Chora Jorge Humberto Ferreira Martins Susana Margarida Sousa Andrade Carlos Alberto dos Reis Ribeiro Maria Graça Monteiro Azevedo Fialho 《International journal of pediatric otorhinolaryngology》2010,74(10):1135-1139
Objectives
Hearing loss is a condition that interferes with the development of the child at a cognitive and language level. Therefore, early diagnosis of deafness is important for (re)habilitation, namely through the use of cochlear implant (CI).The present study aimed at screening CI Portuguese individuals for the presence of mutations in the genes GJB2 and GJB6 (DFNB1 locus), and searching a possible correlation between the genotype and the oral habilitation outcome following implantation.Methods
Our sample included 117 CI individuals implanted longer than 5 years. Sequencing of GJB2 entire coding region was first performed. The presence of deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) was subsequently tested by multiplex PCR. To assess the oral outcome of these individuals, a global score is calculated through a formula that integrates the results of a battery of speech and audiological tests routinely used in ORL services. This global oral performance score was used to test whether individuals with DFNB1-associated deafness perform significantly better than individuals without DFNB1-associated deafness.Results
In 35% of the cases, deafness was clearly associated to DFNB1. The most common mutated allele was c.35delG (85%). Other variants have also been found, namely p.Gly130Ala, p.Asn206Ser, p.Val37Ile, p.Glu47X, p.Arg184Trp, p.Trp24X and the two common GJB6 deletions, del(GJB6-D13S1854) and del(GJB6-D13S1830), the last one identified for the first time in our population. Regarding the oral outcome, after testing the homogeneity of the two groups it could be observed that, in mean, the individuals with DFNB1-associated deafness perform significantly better (p = 0.012) than the individuals without DFNB1-associated deafness.Discussion and conclusion
This first screening of DFNB1 genes in the Portuguese CI population provides clear evidence of the high proportion of DFNB1-associated deafness amongst the Portuguese implanted individuals. DFNB1 status is significantly associated to higher oral performance scores, with DFNB1 individuals performing, on average, 6% better than the individuals without DFNB1-associated deafness. 相似文献20.
Successful cochlear implantation in prelingual profound deafness resulting from the common 233delC mutation of the GJB2 gene in the Japanese 总被引:6,自引:0,他引:6
Matsushiro N Doi K Fuse Y Nagai K Yamamoto K Iwaki T Kawashima T Sawada A Hibino H Kubo T 《The Laryngoscope》2002,112(2):255-261
OBJECTIVES: Recently, we identified three novel mutations of the GJB2 gene in Japanese families with autosomal-recessive non-syndromic deafness.1 Seven of 11 mutated chromosomes (63.6%) contained a 233delC allele, suggesting that the 233delC mutation is the most common mutation of the GJB2 gene in the Japanese population. After it was recognized that cochlear implantation (CI) is of benefit to children with prelingual deafness, we have had a number of prelingual pediatric CI patients. Because children carrying the homozygous 233delC mutation show bilateral prelingual profound deafness, they could be enrolled in the CI program at Osaka University Graduate School of Medicine. The purposes of this study were 1) to analyze the occurrence of the GJB2 mutations in our 15 prelingual pediatric CI patients in whom the cause of non-syndromic deafness was unknown, and 2) to evaluate the auditory function and postoperative speech perception with CI of those GJB2-related deaf subjects. STUDY DESIGN: Retrospective analysis. METHODS: Mutation analysis of the GJB2 gene by direct sequencing was performed with genomic DNA from 15 children born profoundly deaf as a result of unknown causes and implanted with CI. Intraoperative electrically evoked auditory brainstem response (EABR) and intra-/postoperative EAP were measured. The speech perception was evaluated with Infants and Toddlers Meaningful Auditory Integration Scale (IT-MAIS). RESULTS AND CONCLUSIONS: We identified 4 CI patients (26.7%) out of 15 children carrying the homozygous 233delC mutation. Intra- and postoperative evaluation of the auditory system revealed almost intact cochlear and retrocochlear auditory function in these 4 patients. Postoperative auditory testing indicates that their speech perception had become significantly higher in comparison with that of other prelingual CI patients. These results suggest that prelingual deaf children carrying the homozygous 233delC mutation of the GJB2 gene can benefit from CI. 相似文献