人工耳蜗植入群体中耳聋相关基因的检测与分析
|
摘要
新生儿重度听力障碍发病率为1/1000,其中半数与遗传因素相关。常染色体隐性非综合征性耳聋是遗传性耳聋中最常见的类型,大约占遗传性耳聋的80%。到目前为止,己有超过100个耳聋相关基因己被克隆(包括常染色体显性、常染色体隐性、X连锁、Y连锁、线粒体遗传)(The Hereditary Hearing loss Homepage;http://webh01.ua.ac.be/hhh/)。
为了解我国接受人工耳蜗植入群体的分子病因学情况,本课题组自2004年开始,采有候选基因法,对主要的耳聋致病基因GJB2、SLC26A4、线粒体12SrRNA基因进行筛查,以明确突变发生的几率、突变形式和突变热点。
第一部分病人临床资料收集和耳聋相关基因筛查方法
病例收集选取2004年11月至2006年6月我院接受人工耳蜗植入的非综合征性耳聋患者100例及正常对照109例接受GJB2和线粒体12S rRNA基因突变检测。另外选取行高分辨率CT或MRI扫描发现内耳畸形的耳聋患者48例及正常对照50例接受SLC26A4(PDS)基因突变检测。实验方法在进行人工耳蜗植入群体分子病因研究中所使用的材料和方法和策略,包括病例的收集和遗传性耳聋数据库的建立:实验中使用的主要仪器设备、软件和试剂;主要的实验方法和数据分析策略。
第二部分非综合征性耳聋病人GJB2基因突变分析
目的研究重点探讨在接受人工耳蜗植入的病人中,GJB2基因突变发生的几率、突变形式。方法取100例中国人接受人工耳蜗植入的患者及健康对照109例。取外周血提取基因组DNA,经聚合酶链反应一单链构象多态(PCR-SSCP)及直接测序分析。结果41.0%(41/100)的人工耳蜗植入患者发现GJB2基因突变。本研究中共发现突变形式有11种,其中235delC是最常见的突变类型,等位基因频率占全部人工耳蜗植入患者的21.0%(42/200)。187G＞T和230G＞A突变是首次发现的新突变。结论GJB2基因的突变是中国人工耳蜗植入患者主要的致聋基因突变,235delC是其最常见的突变类型。人工耳蜗植入。
第三部分非综合征性耳聋病人线粒体12SrRNA基因突变分析
目的研究接受人工耳蜗植入的耳聋患者中,线粒体12S rRNA基因突变的突变类型和发生几率。方法选取100例接受人工耳蜗植入的非综合征性耳聋患者(语前聋96例,语后聋4例;氨基糖苷类药物使用史者16例),取外周血提取基因组DNA,以PCR方法扩增线粒体12S rRNA基因,扩增产物纯化后直接测序分析突变。结果在有氨基糖苷类药物使用史的16例患者中,检出2例线粒体12S rRNA基因1555A＞G突变,1例线粒体12S rRNA基因突变delT961Cn突变,占全部人工耳蜗植入群体的3%。结论在本研究的人工耳蜗植入群体中,线粒体12S rRNA基因突变不是主要的致病病因。
第四部分前庭导水管扩大及其他内耳畸形病人SLC26A4基因突变分析
目的探讨前庭导水管扩大及其他内耳畸形患者SLC26A4(PDS)基因突变发生的几率、突变类型,以及SLC26A4(PDS)基因突变与各种内耳畸形及术中听神经电诱发复合动作电位(ECAP)检出率之间的关系。方法选取48例伴有内耳畸形的人工耳蜗植入者及50例健康对照。取外周血提取基因组DNA,经聚合酶链反应扩增SLC26A4(PDS)基因全部编码区,包括2～21号外显子,扩增产物纯化后直接测序分析突变。48例患者在人工耳蜗植入术中通过神经反应遥测(NRT)技术,直接近场记录听神经电诱发复合动作电位(ECAP)。结果前庭水管扩大组中70.3%(26/37)、其他内耳畸形组中18.2%(2/11)的患者发现有SLC26A4(PDS)基因突变。本研究中共发现15种突变类型,其中有8种为新发现的类型。IVS7-2A＞G是最常见的SLC26A4(PDS)基因突变类型,45.9%(17/37)的前庭水管扩大患者发现此种突变。在伴内耳畸形的人工耳蜗植入者患者中,未发现SLC26A4(PDS)基因突变与术中听神经电诱发复合动作电位(ECAP)检出率之间有相关性。结论SLC26A4(PDS)基因突变是前庭水管扩大畸形的主要病因,IVS7-2A＞G是其最常见的突变类型。
Severe deafness or hearing impairment affecting about 1 in 1,000 children,half of that is genetic.Non-syndromic autosomal recessive deafness is the most common form of genetic hearing loss,accounts for approximately 80 percent of cases of hereditary deafness.So far more that 100 genes associated with Non-syndromic hearing loss(including dominant and recessive autosomal,X-linked,Y-linked and mitochondrial types of transmission) have been cloned(The Hereditary Hearing loss Homepage, http://wehh01.ua.ac.be/hhh/).
To determine the molecular etiology of cochlear implant recipients, this study focused on the prevalence of candidate genes:GJB2, mitochondrial 12S rRNA and SLC26A4(PDS) gene mutations in patients undergoing cochlear implantation.
Part1:The Methods of Collecting Clinical Date and Screening the Genes of Deafness in Cochlear Implant Recipients
Cases Collection:We enrolled 100 non-syndromic deafness cochlear implant recipients and 109 healthy controls from November,2004 to June,2006 in PUMCH for mutation screening of GJB2 and mitochondrial 12S rRNA gene.We enrolled another 48 Cochlear Implant Recipients with inner ear malformation and 50 healthy controls for mutation screening of SLC26A4(PDS) gene.Materials and Methods:This part demonstrate detailedly the methods and material used in collecting clinical date and screening the genes of deafness in cochlear implant recipients,including the mathods of collecting genetic resource of the cochlear implant recipients and establishing the database of the hereditary hearing imparement;the facility,software and reagent used in this study;and the analysis strategy of the date in the study.
Part2:Screening of the GJB2(Connexin-26) gene
Objective:To determine the prevalence of GJB2 gene mutations in patients undergoing cochlear implantation.
Methods:We enrolled 100 cochlear implant recipients for mutation screening.Genomic DNA was extracted from the blood of all patients, amplified in PCR and analyzed for single strand conformation polymorphism (SSCP) or direct sequencing to detect mutations of GJB2 gene.
Results:The result shows that the GJB2 mutationsare detected in 41.0% (41/100) of the cochlear implant recipients.This study found 11 different variations in the GJB2 gene.The 235de1C mutation was the most prevalent mutation accounting for 21.0%(42/200) in all cochlear implant recipients. 187G＞T and 230G＞A mutations were novel mutation of GJB2 gene in the Chinese population.
Conclusion:Mutations in the GJB2 gene were a major cause of deafness in cochlear implant recipients;the carrier frequency of 235delC mutation was highest.
Part 3:Screening of the Mitochondrial 12SrRNA Gene
Objective To investigate the prevalence of the mitochondrial 12S rRNA gene mutation in Chinese patients received cochlear implantation.
Methods The 100 Chinese patients received cochlear implantation were analyzed in the present study(96 with pre-lingual hearing loss,4 with post-lingual hearing loss).Genomic DNA was extracted from peripheral blood obtained.After PCR amplication,each fragments of the mitochondrial 12S rRNA gene was sequenced in automated DNA sequencer.
Results Only two cases was identified with the mitochondrial 1555 A＞G mutation and One occurrences of the de1T961Cn mutation in the mitochondrial 12S rRNA gene out of 16 patients received aminoglycosides.The deafness mutation was accounting for 3%in all cochlear implant recipients.
Conclution In this study,mutations of the mitochondrial 12S rRNA gene were not the major cause of deafness in cochlear implant recipients.
Part 4:Screening of SLC26A4(PDS) Gene in patients with EVA or others Inner Ear Malformation
Objective:To determine the prevalence of SLC26A4(PDS) gene mutations in Cochlear Implant Recipients with inner ear malformation,and the correlation between SLC26A4(PDS) gene mutations and inner ear malformation and intra-operative testing of the electrically evoked auditory nerve compound action potentials(ECAP).
Methods:48 Cochlear Implant Recipients with temporal bone malformation and 50 health control were enrolled for mutation screening.Genomic DNA was extracted from the blood,amplified in PCR and analyzed for direct sequencing to detect mutations of SLC26A4(PDS) gene.48 Cochlear Implant Recipients were tested intraoperative neural response telemetry(NRT), which measures the electrically evoked auditory nerve compound action potentials(ECAP).
Results:The result shows that the SLC26A4(PDS) mutations are detected in 70.3%(26/37) of the patients with EVA(enlarged vestibular aqueduct), and 18.2%(2/11) of the patients with others malformation of inner ear. Fifteen different mutations were identified,8 of which had never been previously reported.The IVS7-2A＞G mutation was the most prevalent mutation of SLC26A4(PDS) gene accounting for 45.9%(17/37) in the patients with EVA(enlarged vestibular aqueduct).There was no association implied between SLC26A4 mutations ECAP in Cochlear Implant Recipients with inner ear malformation.
Conclusion:In Cochlear Implant Recipients,mutations in the SLC26A4 (PDS) gene was a major cause of EVA,the most common mutation was IVS7-2A＞G.
为了解我国接受人工耳蜗植入群体的分子病因学情况,本课题组自2004年开始,采有候选基因法,对主要的耳聋致病基因GJB2、SLC26A4、线粒体12SrRNA基因进行筛查,以明确突变发生的几率、突变形式和突变热点。
第一部分病人临床资料收集和耳聋相关基因筛查方法
病例收集选取2004年11月至2006年6月我院接受人工耳蜗植入的非综合征性耳聋患者100例及正常对照109例接受GJB2和线粒体12S rRNA基因突变检测。另外选取行高分辨率CT或MRI扫描发现内耳畸形的耳聋患者48例及正常对照50例接受SLC26A4(PDS)基因突变检测。实验方法在进行人工耳蜗植入群体分子病因研究中所使用的材料和方法和策略,包括病例的收集和遗传性耳聋数据库的建立:实验中使用的主要仪器设备、软件和试剂;主要的实验方法和数据分析策略。
第二部分非综合征性耳聋病人GJB2基因突变分析
目的研究重点探讨在接受人工耳蜗植入的病人中,GJB2基因突变发生的几率、突变形式。方法取100例中国人接受人工耳蜗植入的患者及健康对照109例。取外周血提取基因组DNA,经聚合酶链反应一单链构象多态(PCR-SSCP)及直接测序分析。结果41.0%(41/100)的人工耳蜗植入患者发现GJB2基因突变。本研究中共发现突变形式有11种,其中235delC是最常见的突变类型,等位基因频率占全部人工耳蜗植入患者的21.0%(42/200)。187G＞T和230G＞A突变是首次发现的新突变。结论GJB2基因的突变是中国人工耳蜗植入患者主要的致聋基因突变,235delC是其最常见的突变类型。人工耳蜗植入。
第三部分非综合征性耳聋病人线粒体12SrRNA基因突变分析
目的研究接受人工耳蜗植入的耳聋患者中,线粒体12S rRNA基因突变的突变类型和发生几率。方法选取100例接受人工耳蜗植入的非综合征性耳聋患者(语前聋96例,语后聋4例;氨基糖苷类药物使用史者16例),取外周血提取基因组DNA,以PCR方法扩增线粒体12S rRNA基因,扩增产物纯化后直接测序分析突变。结果在有氨基糖苷类药物使用史的16例患者中,检出2例线粒体12S rRNA基因1555A＞G突变,1例线粒体12S rRNA基因突变delT961Cn突变,占全部人工耳蜗植入群体的3%。结论在本研究的人工耳蜗植入群体中,线粒体12S rRNA基因突变不是主要的致病病因。
第四部分前庭导水管扩大及其他内耳畸形病人SLC26A4基因突变分析
目的探讨前庭导水管扩大及其他内耳畸形患者SLC26A4(PDS)基因突变发生的几率、突变类型,以及SLC26A4(PDS)基因突变与各种内耳畸形及术中听神经电诱发复合动作电位(ECAP)检出率之间的关系。方法选取48例伴有内耳畸形的人工耳蜗植入者及50例健康对照。取外周血提取基因组DNA,经聚合酶链反应扩增SLC26A4(PDS)基因全部编码区,包括2～21号外显子,扩增产物纯化后直接测序分析突变。48例患者在人工耳蜗植入术中通过神经反应遥测(NRT)技术,直接近场记录听神经电诱发复合动作电位(ECAP)。结果前庭水管扩大组中70.3%(26/37)、其他内耳畸形组中18.2%(2/11)的患者发现有SLC26A4(PDS)基因突变。本研究中共发现15种突变类型,其中有8种为新发现的类型。IVS7-2A＞G是最常见的SLC26A4(PDS)基因突变类型,45.9%(17/37)的前庭水管扩大患者发现此种突变。在伴内耳畸形的人工耳蜗植入者患者中,未发现SLC26A4(PDS)基因突变与术中听神经电诱发复合动作电位(ECAP)检出率之间有相关性。结论SLC26A4(PDS)基因突变是前庭水管扩大畸形的主要病因,IVS7-2A＞G是其最常见的突变类型。
Severe deafness or hearing impairment affecting about 1 in 1,000 children,half of that is genetic.Non-syndromic autosomal recessive deafness is the most common form of genetic hearing loss,accounts for approximately 80 percent of cases of hereditary deafness.So far more that 100 genes associated with Non-syndromic hearing loss(including dominant and recessive autosomal,X-linked,Y-linked and mitochondrial types of transmission) have been cloned(The Hereditary Hearing loss Homepage, http://wehh01.ua.ac.be/hhh/).
To determine the molecular etiology of cochlear implant recipients, this study focused on the prevalence of candidate genes:GJB2, mitochondrial 12S rRNA and SLC26A4(PDS) gene mutations in patients undergoing cochlear implantation.
Part1:The Methods of Collecting Clinical Date and Screening the Genes of Deafness in Cochlear Implant Recipients
Cases Collection:We enrolled 100 non-syndromic deafness cochlear implant recipients and 109 healthy controls from November,2004 to June,2006 in PUMCH for mutation screening of GJB2 and mitochondrial 12S rRNA gene.We enrolled another 48 Cochlear Implant Recipients with inner ear malformation and 50 healthy controls for mutation screening of SLC26A4(PDS) gene.Materials and Methods:This part demonstrate detailedly the methods and material used in collecting clinical date and screening the genes of deafness in cochlear implant recipients,including the mathods of collecting genetic resource of the cochlear implant recipients and establishing the database of the hereditary hearing imparement;the facility,software and reagent used in this study;and the analysis strategy of the date in the study.
Part2:Screening of the GJB2(Connexin-26) gene
Objective:To determine the prevalence of GJB2 gene mutations in patients undergoing cochlear implantation.
Methods:We enrolled 100 cochlear implant recipients for mutation screening.Genomic DNA was extracted from the blood of all patients, amplified in PCR and analyzed for single strand conformation polymorphism (SSCP) or direct sequencing to detect mutations of GJB2 gene.
Results:The result shows that the GJB2 mutationsare detected in 41.0% (41/100) of the cochlear implant recipients.This study found 11 different variations in the GJB2 gene.The 235de1C mutation was the most prevalent mutation accounting for 21.0%(42/200) in all cochlear implant recipients. 187G＞T and 230G＞A mutations were novel mutation of GJB2 gene in the Chinese population.
Conclusion:Mutations in the GJB2 gene were a major cause of deafness in cochlear implant recipients;the carrier frequency of 235delC mutation was highest.
Part 3:Screening of the Mitochondrial 12SrRNA Gene
Objective To investigate the prevalence of the mitochondrial 12S rRNA gene mutation in Chinese patients received cochlear implantation.
Methods The 100 Chinese patients received cochlear implantation were analyzed in the present study(96 with pre-lingual hearing loss,4 with post-lingual hearing loss).Genomic DNA was extracted from peripheral blood obtained.After PCR amplication,each fragments of the mitochondrial 12S rRNA gene was sequenced in automated DNA sequencer.
Results Only two cases was identified with the mitochondrial 1555 A＞G mutation and One occurrences of the de1T961Cn mutation in the mitochondrial 12S rRNA gene out of 16 patients received aminoglycosides.The deafness mutation was accounting for 3%in all cochlear implant recipients.
Conclution In this study,mutations of the mitochondrial 12S rRNA gene were not the major cause of deafness in cochlear implant recipients.
Part 4:Screening of SLC26A4(PDS) Gene in patients with EVA or others Inner Ear Malformation
Objective:To determine the prevalence of SLC26A4(PDS) gene mutations in Cochlear Implant Recipients with inner ear malformation,and the correlation between SLC26A4(PDS) gene mutations and inner ear malformation and intra-operative testing of the electrically evoked auditory nerve compound action potentials(ECAP).
Methods:48 Cochlear Implant Recipients with temporal bone malformation and 50 health control were enrolled for mutation screening.Genomic DNA was extracted from the blood,amplified in PCR and analyzed for direct sequencing to detect mutations of SLC26A4(PDS) gene.48 Cochlear Implant Recipients were tested intraoperative neural response telemetry(NRT), which measures the electrically evoked auditory nerve compound action potentials(ECAP).
Results:The result shows that the SLC26A4(PDS) mutations are detected in 70.3%(26/37) of the patients with EVA(enlarged vestibular aqueduct), and 18.2%(2/11) of the patients with others malformation of inner ear. Fifteen different mutations were identified,8 of which had never been previously reported.The IVS7-2A＞G mutation was the most prevalent mutation of SLC26A4(PDS) gene accounting for 45.9%(17/37) in the patients with EVA(enlarged vestibular aqueduct).There was no association implied between SLC26A4 mutations ECAP in Cochlear Implant Recipients with inner ear malformation.
Conclusion:In Cochlear Implant Recipients,mutations in the SLC26A4 (PDS) gene was a major cause of EVA,the most common mutation was IVS7-2A＞G.
引文
1 Valvassori GE,Clemis JD.The large vestibular aqueduct syndrome.Laryngoscope,1978,88:723-728.
2 Zelante L,Gasparini P,Estivill X,et al.Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans.Hum Mol Genet,1997,6:1605-1609.
3 Van Camp G,Willems P,Smith RJH.Nonsyndromic hearing impairment:unparalleled heterogeneity.Am J Hum Genet,1997,60:758-764.
4 Murgia A,Orzan E,Polli R,et al.Cx26 deafness:mutation analysis and clinical variability.J Med Genet,1999,36:829-832.
5 陈东野,陈晓巍,曹克利,等.《人工耳蜗植入者连接蛋白26基因(GJB2)突变分析》中华医学杂志2006,86(44)3114-3117。
6 Everett LA,Glaser B,Beck JC,et al.Pendred syndrome is caused by mutations in a putative sulphate transporter gene(PDS).Nature Genet,1997,17:411-422.
7 Scott DA,Wang R,Kreman TM,et al.The Pendred syndrome gene encodes a chloride-iodide transport protein.Nature Genet,1999,21:440-443.
8 The Pendred/BOR Homepage(SLC26A4 Mutations)http://www.healthcare.uiowa.edu/labs/pendredandbor/slcMutations.htm。
9 Valvassori GE,Clemis JD.The large vestibular aqueduct syndrome.Laryngoscope,1978,88:723-728.
10 Cross NC,Stephens SD,Francis M,et al.Computed tomography evaluation of the inner ear as adiagnostic,counselling and management strategy in patients with congenital sensorineural hearing impairment.Clin Otolaryngo1,1999,24:235-238.
11 陈东野,陈晓巍,金昕,等.《伴内耳畸形的人工耳蜗植入患者SLC26A4(PDS)基因突变分析》中华医学杂志2007,87(40)2820-2824。
12 Usami S,Abe S,Shinkawa H,et al.Sensorineural hearing loss caused by mitochondrial DNA mutations:special reference to the 1555A＞G mutation.J Commun Disord,1998,31:423-34;quiz 434-435.
13 田永胜,陈晓巍,陈东野,等.非综合征性耳聋人工耳蜗植入患者的基因分析.中华医学.2007,16,1093-6.
1 Morton N E.Genetic epidemiology of hearing impairment.Ann N Y Acad.Sci 1991,630:16-31.
2 Kelley PM,Harris DJ,Comer BC,et al.Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive(DFNB1) hearing loss.Am J Hum Genet,1998,62:792-799.
3 Zelante L,Gasparini P,Estivill X,et al.Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans.Hum Mol Genet,1997,6:1605-1609.
4 Van Camp G,Willems P,Smith RJH.Nonsyndromic hearing impairment:unparalleled heterogeneity.Am J Hum Genet,1997,60:758-764.
5 Murgia A,Orzan E,Polli R,et al.Cx26 deafness:mutation analysis and clinical variability.J Med Genet,1999,36:829-832.
6 Morell RJ,Kim HJ,Hood LJ,et al.Mutations in the connexin 26 gene(GJB2)among Ashkenazi Jews with nonsyndromic recessive deafness.N Engl J Med,1998,339:1500-1505.
7 Abe S,Usami S,Shinkawa H,et al.Prevalent connexin 26 gene(GJB2) mutations in Japanese.J Med Genet,2000,37:41-43.
8 Liu XZ,Xia X J,Ke XM,et al.The prevalence of connexin 26(GJB2) mutations in the Chinese population.Hum Genet,2002,111:394-397.
9 Brobby GW,M(u|¨)ller-Myhsok B,Horstmann RD.Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa.N Engl J Med,1998,338:548-9.
10 L Van Laer,P Coucke,R F Mueller,et al.A common founder for the 35delG GJB2gene mutation in connexin 26 hearing impairment.J Med Genet,2001,38:515-518.
11 Bauer P W, Geers Ann E, Brenner C, et al. The Effect of GJB2 Allele Variants on Performance After Cochlear Implantation. Laryngoscope,2003,113( 12):2135-2140.
12 Sinnathuray AR, Toner JG, Clarke-Lyttle J, et al. Auditory Perception and Speech Discrimination After Cochlear Implantation in Patients with Connexin 26 (GJB2) Gene-Related Deafness. Otol Neurotol,2004, 25:930-934.
13 Propst EJ, Papsin BC, Stockley TL, er al. Auditory responses in cochlear implant users with and without GJB2 deafness. Laryngoscope..2006,116(2):317-27.
14 Cullen RD, Buchman CA, Brown CJ, et al, Cochlear implantation for children with GJB2-related deafness.Laryngoscope. 2004,114(8): 1415-9.
15 Wiley S, Choo D, Meinzen-Derr J,et al, GJB2 mutations and additional disabilities in a pediatric cochlear implant population. Int J Pediatr Otorhinolaryngol.2006 ,70(3):493-500.
1.Usami S,Abe S,Shinkawa H,et al.Sensorineural hearing loss caused by mitochondrial DNA mutations:special reference to the AI555G mutation.J Commun Disord,1998,31(5):423-434.
2.Yoshida M,Shintani T,Hirao M,et al.Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA.ORL J Otorhinolaryngol Relat Spec,2002,64(3):219-222.
3.田永胜,陈晓巍,陈东野,等.非综合征性耳聋人工耳蜗植入患者的基因分析.中华医学.2007,16,1093-6.
4.Prezant TR,Agapian JV,Bohlman MC,et al.Mitochondrial ribosomal RNA mutation associated with both antibiotioc-induced and non-syndromic deafness.Nat Get,1993,4:289-294.
5.Hamasaki K,Rando RR.Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness. Biochemistry. 1997 Oct 7;36 (40): 12323-8.
6. Hutchin T, Haworth I, Higashi K, et al. A molecular basis for human hypersensitivity to aminoglycoside antibiotics. Nucleic Acids Res.1993 Sep 11;21(18):4174-9.
7. Bacino C, Prezant TR, Bu X, et al. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics. 1995 Jun;5(3):165-72.
8. Casano RA, Johnson DF, Bykhovskaya Y, er al. Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications. Am J Otolaryngol. 1999 May-Jun;20(3):151-6.
9. Noguchi Y, Yashima T, Ito T, et al. Audiovestibular findings in patients with mitochondrial A1555G mutation. Laryngoscope. 2004,Feb. 114(2): 344-8.
10. Yoshida M, Shintani T, Hirao M, et al. Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA. ORL J Otorhinolaryngol Relat Spec. 2002 May-Jun;64(3):219-22.
11. Li Z, Li R, Chen J, et al. Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet.2005 Jun;117(1):9-15. Epub 2005 Apr 20.
12. Usami S, Abe S, Akita J, et al. Prevalence of mitochondrial gene mutations among hearing impaired patients. J Med Genet 2000, 37(1):38-40.
13. Tang HY, Hutcheson E, Neill S, et al.Genetic susceptibility to aminoglycoside ototoxicity: how many are at risk?Genet Med. 2002 Sep-Oct;4(5):336-45.
14. Nadol JB Jr, Young YS, Glynn RJ. Survival of spiral ganglion cells in profound sensorineural hearing loss: implications for cochlear implantation. Ann Otol Rhinol Laryngol. 1989 Jun;98(6):411-6.
15. Tono T, Ushisako Y, Kiyomizu K, et al. Cochlear implantation in a patient with profound hearing loss with the A 1555G mitochondrial mutation. Am J Otol 1998,19: 754-7.
1 Everett LA,Glaser B,Beck JC,et al.Pendred syndrome is caused by mutations in a putative sulphate transporter gene(PDS).Nature Genet,1997,17:411-422.
2 Scott DA,Wang R,Kreman TM,et al.The Pendred syndrome gene encodes a chloride-iodide transport protein.Nature Genet,1999,21:440-443.
3 Scott DA,Wang R,Kreman TM,et al.Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss(DFNB4).Hum Mol Genet,2000,9:1709-1715.
4 The Pendred/BOR Homepage(SLC26A4 Mutations)http://www.healthcare.uiowa.edu/labs/pendredandbor/slcMutations.htm。
5 Valvassori GE,Clemis JD.The large vestibular aqueduct syndrome.Laryngoscope,1978,88:723-728.
6 Cross NC,Stephens SD,Francis M,et al.Computed tomography evaluation of the inner ear asadiagnostic,counselling and management strategy in patients with congenital sensorineural hearing impairment.Clin Otolaryngol,1999,24:235-238.
7 陈东野,陈晓巍,曹克利,等.人工耳蜗植入者连接蛋白26基因(GJB2)突变分析.中华医学杂志,2006,86:3114-3117.
8 Campbell C,Cucci RA,Prasad S,et al.Pendred syndrome,DFNB4,and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.Hum Mutat,2001,17:403-411.
9 TsukamotoK,Suzuki H,HaradaD,et al.Distributionand frequencies of PDS(SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct:a unique spectrum of mutations in Japanese..Eur J Hum Genet,2003,11:916-922.
10 戴扑,韩东一,冯勃,等.大前导水管综合征的基因诊断和SLC26A4基因突变分析.中国耳鼻咽喉头颈外科,2006,13:303-307.
11 Jackler RK, Luxford WM, House WF. Congenital malformations of the inner ear: A classifi cation based on embryogenesis. Laryngoscope, 1987, 97(suppl 40):2-14.
12 Pyle GM. Embryological development and large vestibular aqueduct syndrome. Laryngoscope, 2000, 110: 1837-1842.
13 Chen CW, Chen PJ, ChuanJ H. Specificity of SLC26A4 Mutations in the Pathogenesis of Inner Ear Malformations. Audiol Neurotol , 2005,10:234-242.
14 Fitoz S, Sennaroglu L, Incesulu A, et al. SLC26A4 mutations are associated with a specific inner ear malformation. Int J Pediatr Otorhinolaryngol, 2007,71:479-486.
15 Phelps PD, Coffey RA, Trembath RC, et al. Radiological malformations of the ear in Pendred yndrome. Clin Radiol, 1998, 53: 268-273.
16 Miyamoto RT, Bichey BG, Wynne MK,et al. Cochlear implantation with large vestibular aqueduct syndrome. Laryngoscope. 2002 , Jul;112(7 Pt 1): 1178-82.
17 Wu, C. C. Lee, Y. C.Chen, P. J.et al, Predominance of genetic diagnosis and imaging results as predictors in determining the speech perception performance outcome after cochlear implantation in children. Arch Pediatr Adolesc Med;2008, 162(3):269-76.
18 Madden C, HalstedM, Meinzen-Derr J, et al. The influence of mutations in the SLC26A4 gene on the temporal bone in a population with enlarged vestibular aqueduct. Arch Otolaryngol Head Neck Surg, 2007, 133:162-168.
1 Morton N E,Genetic epidemiology of hearing impairment.Ann N Y Acad.Sci 1991,630:16-31.
2 Kelley PM,Harris DJ,Comer BC,et al.Novel mutations in the connexin 26 gene(GJB2) that cause autosomal recessive(DFNB1) hearing loss.Am J Hum Genet,1998,62:792-799.
3 Zelante L,Gasparini P,Estivill X,et al.Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness(DFNB1) in Mediterraneans.Hum Mol Genet,1997,6:1605-1609.
4 Van Camp G,Willems P,Smith RJH.Nonsyndromic hearing impairment:unparalleled heterogeneity.Am J Hum Genet,1997,60:758-764.
5 Murgia A,Orzan E,Polli R,et al.Cx26 deafness:mutation analysis and clinical variability.J Med Genet,1999,36:829-832.
6 Morell RJ,Kim HJ,Hood LJ,et al.Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness.N Engl J Med,1998,339:1500-1505.
7 Abe S,Usami S,Shinkawa H,et al.Prevalent connexin 26 gene(GJB2)mutations in Japanese.J Med Genet,2000,37:41-43.
8 Liu XZ,Xia XJ,Ke XM,et al.The prevalence of connexin 26(GJB2)mutations in the Chinese population.Hum Genet,2002,111:394-397.
9 陈东野 陈晓巍 曹克利 人工耳蜗植入者连接蛋白26基因(GJB2)突变分析.中华医学杂志.2006 86(44):3114-3117.
10 Brobby GW, Muller-Myhsok B, Horstmann RD. Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa.N Engl J Med,1998, 338:548-9.
11 Prezant TR ,Agapian JV , Bohlman MC , et al . Mitochondrial ribosomal RNA mutation associated with both antibiotioc-induced and non-syndromic deafness. J Nat Get , 1993 , 4 : 289—294.
12 Bacino C, Prezant TR, Bu X, Fournier P, Fischel-Ghodsian N.Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics. 1995 Jun;5(3):165-72.
13 Casano RA, Johnson DF, Bykhovskaya Y, Torricelli F, Bigozzi M, Fischel-Ghodsian N Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications. Am J Otolaryngol.1999 May-Jun;20(3):151-6.
14 Everett LA, Glaser B , Beck JC, et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nature Genet, 1997 ,17: 411-422.
15 Scott DA, Wang R, Kreman TM, et al. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nature Genet, 1999,21: 440-443.
16 Scott DA, Wang R, Kreman TM et al: Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4). Hum Mol Genet 2000; 9: 1709- 1715.
17 Campbell C, Cucci RA, Prasad S, et al. Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat, 2001,17: 403-411.
18 Tsukamoto K, Suzuki H, Harada D, et al. Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese..Eur J Hum Genet,2003,11:916-922.
19 戴扑,韩东一,冯勃,等.大前导水管综合征的基因诊断和SLC26A4基因突变分析.中国耳鼻咽喉头颈外科,2006,13:303-307.
20 陈东野,陈晓巍,金昕,等.《伴内耳畸形的人工耳蜗植入患者SLC26A4(PDS)基因突变分析》中华医学杂志2007年10月30日第87卷第40期2820-2824。
20 Chen C W,Chert PJ,ChuanJ H.Specificity of SLC26A4 Mutations in the Pathogenesis of Inner Ear Malformations.Audiol Neurotol 2005;10:234-242
21 Phelps PD,Coffey RA,Trembath RC et al,Radiological malformations of the ear in Pendred yndrome.Clin Radiol,1998;53:268-273.
22 Sinnathuray AR,Toner JG,Clarke-Lyttle J,et al.Auditory Perception and Speech Discrimination After Cochlear Implantation in Patients with Connexin 26(GJB2) Gene-Related Deafness.Otol Neurotol,2004,25:930-934.
23 Lustig LR,Lin D,Venick H,et al.GJB2 gene mutations in cochlear implant recipients:prevalence and impact on outcome.Arch Otolaryngol Head Neck Surg,2004;130(5):541-546.
24 Taitelbaum-Swead R,Brownstein Z,Muchnik C,et al.Connexin-associated deafness and speech perception outcome of cochlear implantation.Arch Otolaryngol Head Neck Surg,2006;132(5):495-500.
25 Dahl HH,Wake M,Sarant J,et al.Language and speech perception outcomes in hearing-impaired children with and without connexin 26mutations.Audiol Neurootol,2003;8(5):263-268.
26 Green GE,Scott DA,McDonald JM,et al.Performance of cochlear implant recipients with GJB2-related deafness.Am J Med Genet,2002;109(3):167-170.
27 Fukushima K,Sugata K,Kasai N,et al.Better speech performance in cochlear implant patients with GJB2-related deafness.Int J Pediatr Otorhinolaryngol,2002;62(2):151-157.
28 Matsushiro N, Doi K, Fuse Y, et al. Successful cochlear implantation in prelingual profound deafness resulting from the common 233delC mutation of the GJB2 gene in the Japanese. Laryngoscope, 2002;112(2):255-261.
29 Wu, C. C. Lee, Y. C.Chen, P. J. et al, Predominance of genetic diagnosis and imaging results as predictors in determining the speech perception performance outcome after cochlear implantation in children. Arch Pediatr Adolesc Med;2008, 162(3):269-76.
30 Propst EJ, Papsin BC, Stockley TL, er al. Auditory responses in cochlear implant users with and without GJB2 deafness.Laryngoscope.. 2006, 116(2):317-27.
31 Cullen RD, Buchman CA, Brown CJ, et al, Cochlear implantation for children with GJB2-related deafness. Laryngoscope. 2004, 114(8):1415-9.
32 Wiley S, Choo D, Meinzen-Derr J, et al, GJB2 mutations and additional disabilities in a pediatric cochlear implant population. Int J Pediatr Otorhinolaryngol. 2006 , 70(3):493-500.
33 Nadol JB Jr, Young YS, Glynn RJ. Survival of spiral ganglion cells in profound sensorineural hearing loss: implications for cochlear implantation. Ann Otol Rhinol Laryngol. 1989 Jun;98(6):411-6.
34 Tono T, Ushisako Y, Kiyomizu K, et al. Cochlear implantation in a patient with profound hearing loss with the A 1555G mitochondrial mutation.Am J Otol 1998,19: 754-7.
35 Miyamoto RT, Bichey BG, Wynne MK,et al. Cochlear implantation with large vestibular aqueduct syndrome. Laryngoscope. 2002 , Jul;112(7 Pt 1): 1178-82.
36 Rouillon I, Marcolla A, Roux I, et al. Results of cochlear implantation in two children with mutations in the OTOF gene. Int J Pediatr Otorhinolaryngol. 2006, 70(4):689-696.
2 Zelante L,Gasparini P,Estivill X,et al.Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans.Hum Mol Genet,1997,6:1605-1609.
3 Van Camp G,Willems P,Smith RJH.Nonsyndromic hearing impairment:unparalleled heterogeneity.Am J Hum Genet,1997,60:758-764.
4 Murgia A,Orzan E,Polli R,et al.Cx26 deafness:mutation analysis and clinical variability.J Med Genet,1999,36:829-832.
5 陈东野,陈晓巍,曹克利,等.《人工耳蜗植入者连接蛋白26基因(GJB2)突变分析》中华医学杂志2006,86(44)3114-3117。
6 Everett LA,Glaser B,Beck JC,et al.Pendred syndrome is caused by mutations in a putative sulphate transporter gene(PDS).Nature Genet,1997,17:411-422.
7 Scott DA,Wang R,Kreman TM,et al.The Pendred syndrome gene encodes a chloride-iodide transport protein.Nature Genet,1999,21:440-443.
8 The Pendred/BOR Homepage(SLC26A4 Mutations)http://www.healthcare.uiowa.edu/labs/pendredandbor/slcMutations.htm。
9 Valvassori GE,Clemis JD.The large vestibular aqueduct syndrome.Laryngoscope,1978,88:723-728.
10 Cross NC,Stephens SD,Francis M,et al.Computed tomography evaluation of the inner ear as adiagnostic,counselling and management strategy in patients with congenital sensorineural hearing impairment.Clin Otolaryngo1,1999,24:235-238.
11 陈东野,陈晓巍,金昕,等.《伴内耳畸形的人工耳蜗植入患者SLC26A4(PDS)基因突变分析》中华医学杂志2007,87(40)2820-2824。
12 Usami S,Abe S,Shinkawa H,et al.Sensorineural hearing loss caused by mitochondrial DNA mutations:special reference to the 1555A＞G mutation.J Commun Disord,1998,31:423-34;quiz 434-435.
13 田永胜,陈晓巍,陈东野,等.非综合征性耳聋人工耳蜗植入患者的基因分析.中华医学.2007,16,1093-6.
1 Morton N E.Genetic epidemiology of hearing impairment.Ann N Y Acad.Sci 1991,630:16-31.
2 Kelley PM,Harris DJ,Comer BC,et al.Novel mutations in the connexin 26 gene (GJB2) that cause autosomal recessive(DFNB1) hearing loss.Am J Hum Genet,1998,62:792-799.
3 Zelante L,Gasparini P,Estivill X,et al.Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness (DFNB1) in Mediterraneans.Hum Mol Genet,1997,6:1605-1609.
4 Van Camp G,Willems P,Smith RJH.Nonsyndromic hearing impairment:unparalleled heterogeneity.Am J Hum Genet,1997,60:758-764.
5 Murgia A,Orzan E,Polli R,et al.Cx26 deafness:mutation analysis and clinical variability.J Med Genet,1999,36:829-832.
6 Morell RJ,Kim HJ,Hood LJ,et al.Mutations in the connexin 26 gene(GJB2)among Ashkenazi Jews with nonsyndromic recessive deafness.N Engl J Med,1998,339:1500-1505.
7 Abe S,Usami S,Shinkawa H,et al.Prevalent connexin 26 gene(GJB2) mutations in Japanese.J Med Genet,2000,37:41-43.
8 Liu XZ,Xia X J,Ke XM,et al.The prevalence of connexin 26(GJB2) mutations in the Chinese population.Hum Genet,2002,111:394-397.
9 Brobby GW,M(u|¨)ller-Myhsok B,Horstmann RD.Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa.N Engl J Med,1998,338:548-9.
10 L Van Laer,P Coucke,R F Mueller,et al.A common founder for the 35delG GJB2gene mutation in connexin 26 hearing impairment.J Med Genet,2001,38:515-518.
11 Bauer P W, Geers Ann E, Brenner C, et al. The Effect of GJB2 Allele Variants on Performance After Cochlear Implantation. Laryngoscope,2003,113( 12):2135-2140.
12 Sinnathuray AR, Toner JG, Clarke-Lyttle J, et al. Auditory Perception and Speech Discrimination After Cochlear Implantation in Patients with Connexin 26 (GJB2) Gene-Related Deafness. Otol Neurotol,2004, 25:930-934.
13 Propst EJ, Papsin BC, Stockley TL, er al. Auditory responses in cochlear implant users with and without GJB2 deafness. Laryngoscope..2006,116(2):317-27.
14 Cullen RD, Buchman CA, Brown CJ, et al, Cochlear implantation for children with GJB2-related deafness.Laryngoscope. 2004,114(8): 1415-9.
15 Wiley S, Choo D, Meinzen-Derr J,et al, GJB2 mutations and additional disabilities in a pediatric cochlear implant population. Int J Pediatr Otorhinolaryngol.2006 ,70(3):493-500.
1.Usami S,Abe S,Shinkawa H,et al.Sensorineural hearing loss caused by mitochondrial DNA mutations:special reference to the AI555G mutation.J Commun Disord,1998,31(5):423-434.
2.Yoshida M,Shintani T,Hirao M,et al.Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA.ORL J Otorhinolaryngol Relat Spec,2002,64(3):219-222.
3.田永胜,陈晓巍,陈东野,等.非综合征性耳聋人工耳蜗植入患者的基因分析.中华医学.2007,16,1093-6.
4.Prezant TR,Agapian JV,Bohlman MC,et al.Mitochondrial ribosomal RNA mutation associated with both antibiotioc-induced and non-syndromic deafness.Nat Get,1993,4:289-294.
5.Hamasaki K,Rando RR.Specific binding of aminoglycosides to a human rRNA construct based on a DNA polymorphism which causes aminoglycoside-induced deafness. Biochemistry. 1997 Oct 7;36 (40): 12323-8.
6. Hutchin T, Haworth I, Higashi K, et al. A molecular basis for human hypersensitivity to aminoglycoside antibiotics. Nucleic Acids Res.1993 Sep 11;21(18):4174-9.
7. Bacino C, Prezant TR, Bu X, et al. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics. 1995 Jun;5(3):165-72.
8. Casano RA, Johnson DF, Bykhovskaya Y, er al. Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications. Am J Otolaryngol. 1999 May-Jun;20(3):151-6.
9. Noguchi Y, Yashima T, Ito T, et al. Audiovestibular findings in patients with mitochondrial A1555G mutation. Laryngoscope. 2004,Feb. 114(2): 344-8.
10. Yoshida M, Shintani T, Hirao M, et al. Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA. ORL J Otorhinolaryngol Relat Spec. 2002 May-Jun;64(3):219-22.
11. Li Z, Li R, Chen J, et al. Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet.2005 Jun;117(1):9-15. Epub 2005 Apr 20.
12. Usami S, Abe S, Akita J, et al. Prevalence of mitochondrial gene mutations among hearing impaired patients. J Med Genet 2000, 37(1):38-40.
13. Tang HY, Hutcheson E, Neill S, et al.Genetic susceptibility to aminoglycoside ototoxicity: how many are at risk?Genet Med. 2002 Sep-Oct;4(5):336-45.
14. Nadol JB Jr, Young YS, Glynn RJ. Survival of spiral ganglion cells in profound sensorineural hearing loss: implications for cochlear implantation. Ann Otol Rhinol Laryngol. 1989 Jun;98(6):411-6.
15. Tono T, Ushisako Y, Kiyomizu K, et al. Cochlear implantation in a patient with profound hearing loss with the A 1555G mitochondrial mutation. Am J Otol 1998,19: 754-7.
1 Everett LA,Glaser B,Beck JC,et al.Pendred syndrome is caused by mutations in a putative sulphate transporter gene(PDS).Nature Genet,1997,17:411-422.
2 Scott DA,Wang R,Kreman TM,et al.The Pendred syndrome gene encodes a chloride-iodide transport protein.Nature Genet,1999,21:440-443.
3 Scott DA,Wang R,Kreman TM,et al.Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss(DFNB4).Hum Mol Genet,2000,9:1709-1715.
4 The Pendred/BOR Homepage(SLC26A4 Mutations)http://www.healthcare.uiowa.edu/labs/pendredandbor/slcMutations.htm。
5 Valvassori GE,Clemis JD.The large vestibular aqueduct syndrome.Laryngoscope,1978,88:723-728.
6 Cross NC,Stephens SD,Francis M,et al.Computed tomography evaluation of the inner ear asadiagnostic,counselling and management strategy in patients with congenital sensorineural hearing impairment.Clin Otolaryngol,1999,24:235-238.
7 陈东野,陈晓巍,曹克利,等.人工耳蜗植入者连接蛋白26基因(GJB2)突变分析.中华医学杂志,2006,86:3114-3117.
8 Campbell C,Cucci RA,Prasad S,et al.Pendred syndrome,DFNB4,and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations.Hum Mutat,2001,17:403-411.
9 TsukamotoK,Suzuki H,HaradaD,et al.Distributionand frequencies of PDS(SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct:a unique spectrum of mutations in Japanese..Eur J Hum Genet,2003,11:916-922.
10 戴扑,韩东一,冯勃,等.大前导水管综合征的基因诊断和SLC26A4基因突变分析.中国耳鼻咽喉头颈外科,2006,13:303-307.
11 Jackler RK, Luxford WM, House WF. Congenital malformations of the inner ear: A classifi cation based on embryogenesis. Laryngoscope, 1987, 97(suppl 40):2-14.
12 Pyle GM. Embryological development and large vestibular aqueduct syndrome. Laryngoscope, 2000, 110: 1837-1842.
13 Chen CW, Chen PJ, ChuanJ H. Specificity of SLC26A4 Mutations in the Pathogenesis of Inner Ear Malformations. Audiol Neurotol , 2005,10:234-242.
14 Fitoz S, Sennaroglu L, Incesulu A, et al. SLC26A4 mutations are associated with a specific inner ear malformation. Int J Pediatr Otorhinolaryngol, 2007,71:479-486.
15 Phelps PD, Coffey RA, Trembath RC, et al. Radiological malformations of the ear in Pendred yndrome. Clin Radiol, 1998, 53: 268-273.
16 Miyamoto RT, Bichey BG, Wynne MK,et al. Cochlear implantation with large vestibular aqueduct syndrome. Laryngoscope. 2002 , Jul;112(7 Pt 1): 1178-82.
17 Wu, C. C. Lee, Y. C.Chen, P. J.et al, Predominance of genetic diagnosis and imaging results as predictors in determining the speech perception performance outcome after cochlear implantation in children. Arch Pediatr Adolesc Med;2008, 162(3):269-76.
18 Madden C, HalstedM, Meinzen-Derr J, et al. The influence of mutations in the SLC26A4 gene on the temporal bone in a population with enlarged vestibular aqueduct. Arch Otolaryngol Head Neck Surg, 2007, 133:162-168.
1 Morton N E,Genetic epidemiology of hearing impairment.Ann N Y Acad.Sci 1991,630:16-31.
2 Kelley PM,Harris DJ,Comer BC,et al.Novel mutations in the connexin 26 gene(GJB2) that cause autosomal recessive(DFNB1) hearing loss.Am J Hum Genet,1998,62:792-799.
3 Zelante L,Gasparini P,Estivill X,et al.Connexin26 mutations associated with the most common form of non-syndromic neurosensory autosomal recessive deafness(DFNB1) in Mediterraneans.Hum Mol Genet,1997,6:1605-1609.
4 Van Camp G,Willems P,Smith RJH.Nonsyndromic hearing impairment:unparalleled heterogeneity.Am J Hum Genet,1997,60:758-764.
5 Murgia A,Orzan E,Polli R,et al.Cx26 deafness:mutation analysis and clinical variability.J Med Genet,1999,36:829-832.
6 Morell RJ,Kim HJ,Hood LJ,et al.Mutations in the connexin 26 gene (GJB2) among Ashkenazi Jews with nonsyndromic recessive deafness.N Engl J Med,1998,339:1500-1505.
7 Abe S,Usami S,Shinkawa H,et al.Prevalent connexin 26 gene(GJB2)mutations in Japanese.J Med Genet,2000,37:41-43.
8 Liu XZ,Xia XJ,Ke XM,et al.The prevalence of connexin 26(GJB2)mutations in the Chinese population.Hum Genet,2002,111:394-397.
9 陈东野 陈晓巍 曹克利 人工耳蜗植入者连接蛋白26基因(GJB2)突变分析.中华医学杂志.2006 86(44):3114-3117.
10 Brobby GW, Muller-Myhsok B, Horstmann RD. Connexin 26 R143W mutation associated with recessive nonsyndromic sensorineural deafness in Africa.N Engl J Med,1998, 338:548-9.
11 Prezant TR ,Agapian JV , Bohlman MC , et al . Mitochondrial ribosomal RNA mutation associated with both antibiotioc-induced and non-syndromic deafness. J Nat Get , 1993 , 4 : 289—294.
12 Bacino C, Prezant TR, Bu X, Fournier P, Fischel-Ghodsian N.Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics. 1995 Jun;5(3):165-72.
13 Casano RA, Johnson DF, Bykhovskaya Y, Torricelli F, Bigozzi M, Fischel-Ghodsian N Inherited susceptibility to aminoglycoside ototoxicity: genetic heterogeneity and clinical implications. Am J Otolaryngol.1999 May-Jun;20(3):151-6.
14 Everett LA, Glaser B , Beck JC, et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nature Genet, 1997 ,17: 411-422.
15 Scott DA, Wang R, Kreman TM, et al. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nature Genet, 1999,21: 440-443.
16 Scott DA, Wang R, Kreman TM et al: Functional differences of the PDS gene product are associated with phenotypic variation in patients with Pendred syndrome and non-syndromic hearing loss (DFNB4). Hum Mol Genet 2000; 9: 1709- 1715.
17 Campbell C, Cucci RA, Prasad S, et al. Pendred syndrome, DFNB4, and PDS/SLC26A4 identification of eight novel mutations and possible genotype-phenotype correlations. Hum Mutat, 2001,17: 403-411.
18 Tsukamoto K, Suzuki H, Harada D, et al. Distribution and frequencies of PDS (SLC26A4) mutations in Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct: a unique spectrum of mutations in Japanese..Eur J Hum Genet,2003,11:916-922.
19 戴扑,韩东一,冯勃,等.大前导水管综合征的基因诊断和SLC26A4基因突变分析.中国耳鼻咽喉头颈外科,2006,13:303-307.
20 陈东野,陈晓巍,金昕,等.《伴内耳畸形的人工耳蜗植入患者SLC26A4(PDS)基因突变分析》中华医学杂志2007年10月30日第87卷第40期2820-2824。
20 Chen C W,Chert PJ,ChuanJ H.Specificity of SLC26A4 Mutations in the Pathogenesis of Inner Ear Malformations.Audiol Neurotol 2005;10:234-242
21 Phelps PD,Coffey RA,Trembath RC et al,Radiological malformations of the ear in Pendred yndrome.Clin Radiol,1998;53:268-273.
22 Sinnathuray AR,Toner JG,Clarke-Lyttle J,et al.Auditory Perception and Speech Discrimination After Cochlear Implantation in Patients with Connexin 26(GJB2) Gene-Related Deafness.Otol Neurotol,2004,25:930-934.
23 Lustig LR,Lin D,Venick H,et al.GJB2 gene mutations in cochlear implant recipients:prevalence and impact on outcome.Arch Otolaryngol Head Neck Surg,2004;130(5):541-546.
24 Taitelbaum-Swead R,Brownstein Z,Muchnik C,et al.Connexin-associated deafness and speech perception outcome of cochlear implantation.Arch Otolaryngol Head Neck Surg,2006;132(5):495-500.
25 Dahl HH,Wake M,Sarant J,et al.Language and speech perception outcomes in hearing-impaired children with and without connexin 26mutations.Audiol Neurootol,2003;8(5):263-268.
26 Green GE,Scott DA,McDonald JM,et al.Performance of cochlear implant recipients with GJB2-related deafness.Am J Med Genet,2002;109(3):167-170.
27 Fukushima K,Sugata K,Kasai N,et al.Better speech performance in cochlear implant patients with GJB2-related deafness.Int J Pediatr Otorhinolaryngol,2002;62(2):151-157.
28 Matsushiro N, Doi K, Fuse Y, et al. Successful cochlear implantation in prelingual profound deafness resulting from the common 233delC mutation of the GJB2 gene in the Japanese. Laryngoscope, 2002;112(2):255-261.
29 Wu, C. C. Lee, Y. C.Chen, P. J. et al, Predominance of genetic diagnosis and imaging results as predictors in determining the speech perception performance outcome after cochlear implantation in children. Arch Pediatr Adolesc Med;2008, 162(3):269-76.
30 Propst EJ, Papsin BC, Stockley TL, er al. Auditory responses in cochlear implant users with and without GJB2 deafness.Laryngoscope.. 2006, 116(2):317-27.
31 Cullen RD, Buchman CA, Brown CJ, et al, Cochlear implantation for children with GJB2-related deafness. Laryngoscope. 2004, 114(8):1415-9.
32 Wiley S, Choo D, Meinzen-Derr J, et al, GJB2 mutations and additional disabilities in a pediatric cochlear implant population. Int J Pediatr Otorhinolaryngol. 2006 , 70(3):493-500.
33 Nadol JB Jr, Young YS, Glynn RJ. Survival of spiral ganglion cells in profound sensorineural hearing loss: implications for cochlear implantation. Ann Otol Rhinol Laryngol. 1989 Jun;98(6):411-6.
34 Tono T, Ushisako Y, Kiyomizu K, et al. Cochlear implantation in a patient with profound hearing loss with the A 1555G mitochondrial mutation.Am J Otol 1998,19: 754-7.
35 Miyamoto RT, Bichey BG, Wynne MK,et al. Cochlear implantation with large vestibular aqueduct syndrome. Laryngoscope. 2002 , Jul;112(7 Pt 1): 1178-82.
36 Rouillon I, Marcolla A, Roux I, et al. Results of cochlear implantation in two children with mutations in the OTOF gene. Int J Pediatr Otorhinolaryngol. 2006, 70(4):689-696.