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1.
Prevalence of GJB2 mutations and the del(GJB6-D13S1830) in Argentinean non-syndromic deaf patients 总被引:2,自引:0,他引:2
Dalamón V Béhèran A Diamante F Pallares N Diamante V Elgoyhen AB 《Hearing research》2005,207(1-2):43-49
Genetically caused congenital deafness is a common trait affecting 1 in 2000 children and it is predominantly inherited in an autosomal recessive fashion. Several mutations in the GJB2 gene and a deletion of 342 kb in GJB6 (delGJB6-D13S1830) have been identified worldwide in patients with hearing impairment. The aim of this study was to determine the prevalence of these mutations in Argentina. Non-syndromic 46 probands (17 familial and 29 sporadic cases) were genetically evaluated. Mutations in GJB2 and/or delGJB6-D13S1830 were found in 19 patients, accounting for 41.3% of the sample. Of the 46 patients investigated in this study, 12 (26.1%) were diagnosed to carry sequence variations in both alleles; all but one, were considered causative for hearing impairment in those patients. In 7 out of 46 patients (15.2%) only one mutant allele was detected. Of their 38 chromosomes, 71% resulted with mutations in the GJB2 gene and 11% in GJB6. The most frequent mutation in GJB2 (24%) was c.35delG (11% homozygous and 13% heterozygous and compound heterozygous). In addition, 11 sequence variations different from c.35delG, were identified in the coding region of the GJB2 gene: T8M, V27I, M34T, E47X, R75W, W77R, I82M, L90P, E129K, V153I, M163V. The delGJB6-D13S1830 mutation was found in 4 patients (9%), 3 of them associated with GJB2 mutations, resulting in compound heterozygous for the DFNB1 locus. The present study demonstrates that mutations in the GJB2 gene and the delGJB6-D13S1830 are prevalent in the Argentinean population. 相似文献
2.
Frei K Ramsebner R Lucas T Baumgartner WD Schoefer C Wachtler FJ Kirschhofer K 《Hearing research》2004,196(1-2):115-118
Genetically caused congenital deafness is a common trait affecting 1 in 2000 newborn children and is predominantly inherited in an autosomal recessive fashion. Genes such as the gap junction protein beta 2 (GJB2) encoding for Connexin (Cx26) and GJB6 (Cx30) are known to cause sensorineural deafness. Autosomal recessive deafness has been linked both to the monogenetic occurrence of mutated GJB2 or the GJB6 deletion del(GJB6-D13S1830) and digenic GJB2/del(GJB6-D13S1830) inheritance. Monogenetic GJB2 alterations are responsible for 25.5% of deafness in the eastern Austrian population. An additional 9.8% are heterozygous carriers of a single GJB2 mutation which is not responsible for deafness alone. Del(GJB6-D13S1830) and GJB2/del(GJB6-D13S1830) mutations have been shown to be the second most frequent cause of deafness in different populations. To address the question of the relevance of mutations in GJB6 either as a monogenetic or a digenic GJB2/del(GJB6-D13S1830) cause of deafness in this population, 76 unrelated individuals (33 families and 43 sporadic cases) were screened using PCR strategies. Similar to studies in other hard of hearing populations with similar or lower carrier frequencies of single GJB2 mutations, the presence of del(GJB6-D13S1830) was not detected in any individual within the patient group. Data therefore exclude a digenetic association of del(GJB6-D13S1830) with heterozygous GJB2 mutations as a cause of deafness in a representative sample of the population from Eastern Austria. 相似文献
3.
Prevalence of the GJB2 mutations and the del(GJB6-D13S1830) mutation in Brazilian patients with deafness 总被引:1,自引:0,他引:1
Belintani Piatto V Maria Goloni Bertollo E Lúcia Sartorato E Victor Maniglia J 《Hearing research》2004,196(1-2):87-93
Mutations in the GJB2 gene are the most common cause of sensorineural non-syndromic deafness in different populations. One specific mutation, 35delG, has accounted for the majority of the mutations detected in the GJB2 gene in many countries. The aim of this study was to determine the prevalence of GJB2 mutations and the del(GJB6-D13S1830) mutation in non-syndromic deaf Brazilians. The 33 unrelated probands were examined by clinical evaluation to exclude syndromic forms of deafness. Mutation analysis in the GJB2 gene and the testing for the del(GJB6-D13S1830) were performed in both the patients and their family members. The 35delG mutation was found in nine of the probands or in 14 of the mutated alleles. The V37I mutation and the del(GJB6-D13S1830) mutation were also found in two patients, both are compound heterozygote with 35delG mutation. These findings strengthen the importance of genetic diagnosis, providing early treatment, and genetic counseling of deaf patients. 相似文献
4.
Occurrence of del(GIB6-D13S1830) mutation in Italian non-syndromic hearing loss patients carrying a single GJB2 mutated allele 总被引:1,自引:0,他引:1
Gualandi E Ravani A Berto A Burdo S Trevisi P Ferlini A Martini A Calzolari E 《Acta oto-laryngologica. Supplementum》2004,(552):29-34
Molecular screening for GJB2 (connexin 26) mutations represents the standard diagnostic approach for the genotype definition of non-syndromic deafness. Nevertheless, a single GJB2 pathogenic mutation is detectable in a relevant number of cases, therefore failing to explain the phenotype. We aimed at assessing the occurrence of the recently described del(GIB6-D13S1830) mutation, occurring in the connexin 30 gene, in a group of Italian hearing-impaired patients carrying a single GJB2 mutated allele. A total of 59 non-syndromic hearing loss (NSHL) patients were screened for GJB2 mutations. Among these, nine NSHL patients were found to be heterozygous for a single GJB2 mutation. These patients, heterozygotes for different GJB2 mutated alleles (35delG, L90P, M34T, V153I), together with 11 additional 35delG/neg cases previously described, were studied for the presence of the del(GIB6-D13S1830) mutation. Two double heterozygotes del(GIB6-D13S1830)/35delG were identified. In both cases the degree of hearing loss was profound. Furthermore, GJB2 molecular screening led to the identification of a novel change (T55G) occurring in compound heterozygosity with the V37I mutation. In conclusion, our data suggest a significant frequency of del(GIB6-D13S1830) mutation in Italian hearing-impaired subjects (10% of unexplained GJB2 heterozygotes) similar to that reported in other European countries. 相似文献
5.
Esmaeili M Bonyadi M Nejadkazem M 《International journal of pediatric otorhinolaryngology》2007,71(6):869-873
OBJECTIVE: DFNB1 locus has been reported as a major cause of autosomal recessive non-syndromic hearing loss (ARNSHL) worldwide. 35delG and del(GJB6-D13S1830) are thought to be two common mutations in this locus among Caucasians. The aim of this study is to determine the significance of these two mutations in aetiology of ARNSHL in Iran. METHODS: One hundred and thirty-three unrelated patients with ARNSHL were tested by using multiplex allele-specific PCR assay after validation by positive control samples. RESULTS: The frequency of 35delG was about 18.5%, however, del(GJB6-D13S1830) was not found in the studied patients. Parental consanguinity was observed in 50% of 35delG-mutated families. CONCLUSIONS: Our results support founder effect regarding these mutations. 相似文献
6.
HAN Ming-kun HAN Dong-yi GUO Yu-fen LI Qing-zhong ZHAO Ya-li RAO Shao-qi YUAN Hu ZONG Liang GUAN Jing XU Bai-cheng WANG Da-yong LAN lan WANG Qiu-ju 《中华耳科学杂志(英文版)》2007,2(1):18-22
The GJB2 gene(connexin 26) has been shown to be responsible for DFNB1 and DFNA3. We screened the GJB2 gene in 488 patients with prelingual deafness(Group 1), 124 with postlingual deafness(Group 2), and 117 normal hearing subjects(Group 3). We found that, in Group 1, 65 patients(13.32%) were homozygotes or compound heterozygotes and 51 patients (10.45%) carried a single pathogenic mutation. The 235delC mutation was the most frequent mutation, accounting for 73.22% of the known pathogenic alleles in Group 1. No homozygotes or compound heterozygotes were detected in Group 2 or Group 3. Some postlingual deaf patients (2.42%) and normal hearing subjects(4.27%) were 235delC carriers. Our preliminary data indicate that 235delC, the most frequent mutation identified in this study, is a major cause for prelingual deafness. 相似文献
7.
《International journal of pediatric otorhinolaryngology》2014,78(12):2107-2112
ObjectivesMutations in the DFNB1 locus are the most common cause of autosomal-recessive nonsyndromic hearing loss (ARNSHL) worldwide. The aim of this study was to identify the most frequent mutations in patients with ARNSHL who reside in Northeastern Mexico.MethodsWe determined the nucleotide sequence the coding region of GJB2 of 78 patients with ARNSHL. Polymerase chain reaction assays were used to detect the GJB2 IVS1 + 1G > A mutation and deletions within GJB6.ResultsGJB2 mutations were detected in 9.6% of the alleles, and c.35delG was the most frequent. Six other less-frequent mutations were detected, including an extremely rare variant (c.645_648delTAGA), a novel mutation (c.35G > A), and one of possible Mexican origin (c.34G > T). GJB6 deletions and GJB2 IVS1 + 1G > A were not detected.ConclusionsThese data suggest that mutations in the DFNB1 locus are a rare cause of ARNSHL among the population of Northeastern Mexico. This confirms the genetic heterogeneity of this condition and indicates that further research is required to determine the other mechanisms of pathogenesis of ARNSHL in Mexicans. 相似文献
8.
Hayashi C Funayama M Li Y Kamiya K Kawano A Suzuki M Hattori N Ikeda K 《International journal of pediatric otorhinolaryngology》2011,75(2):211-214
Objective
GJB2 (gap junction protein, beta 2, 26 kDa: connexin 26) is a gap junction protein gene that has been implicated in many cases of autosomal recessive non-syndromic deafness. Point and deletion mutations in GJB2 are the most frequent cause of non-syndromic deafness across racial groups. To clarify the relation between profound non-syndromic deafness and GJB2 mutation in Japanese children, we performed genetic testing for GJB2.Methods
We conducted mutation screening employing PCR and direct sequencing for GJB2 in 126 children who had undergone cochlear implantation with congenital deafness.Results
We detected 10 mutations, including two unreported mutations (p.R32S and p.P225L) in GJB2. We identified the highest-frequency mutation (c.235delC: 44.8%) and other nonsense or truncating mutations, as in previous studies. However, in our research, p.R143W, which is one of the missense mutations, may also show an important correlation with severe deafness.Conclusion
Our results suggest that the frequencies of mutations in GJB2 and GJB6 deletions differ among cohorts. Thus, our report is an important study of GJB2 in Japanese children with profound non-syndromic deafness. 相似文献9.
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11.
Bhalla S Sharma R Khandelwal G Panda NK Khullar M 《International journal of pediatric otorhinolaryngology》2011,75(3):356-359
Objective
Hearing loss is the most frequent sensory defect in human being. Genetic factors account for at least half of all cases of profound congenital deafness. The 13q11-q12 region contains the GJB2 and GJB6 genes, which code connexin 26 (CX26) and connexin 30 (CX30) proteins, respectively. Mutations in the gene GJB2, encoding the gap junction protein connexin 26, are considered to be responsible for up to 50% of familial cases of autosomal recessive non-syndromic hearing loss and for up to 15-30% of the sporadic cases. It has also been reported that mutations in the GJB6 gene contribute to autosomal recessive and autosomal dominant hearing defects in many populations. The 342-kb deletion [del(GJB6-D13S1830)] of the Cx30 gene is the second most common connexin mutation after the CX26 mutations in some NSHL populations. The aim of this study was to screen GJB6 gene mutations in Asian Indian patients with autosomal non-syndromic hearing loss.Methods
We screened 203 non-syndromic hearing loss patients, who were negative for homozygous mutations in GJB2 gene, for GJB6-D13S1830 deletion and mutations in coding regions of GJB6 using polymerase chain reaction, denaturing high performance liquid chromatography and direct sequencing.Results
No deleterious mutation in GJB6 gene was detected in our study cohort.Conclusion
The present data demonstrated that mutations in the GJB6 gene are unlikely to be a major cause of non-syndromic deafness in Asian Indians. 相似文献12.
目的 研究云南地区非综合征性聋患儿GJB2、SLC26A4和线粒体DNA12S rRNA基因的突变情况,了解其遗传特征。方法 采集2010年1月~2014年5月我院门诊散发的139例先天性重度和极重度非综合征性感音神经性聋患儿外周血,提取DNA。应用飞行质谱技术对GJB2、SLC26A4和线粒体DNA12S rRNA编码区域中8个突变位点进行检测,包括GJB2(35delG、167delT、176-191dell6、235delC、299-300delAT),SLC26A4(281C→T、589G→A、IVs7-2A→G、1174A→T、1226G→A、1229C→T、IVSl5+5G→A、1975G→C、2027T→A、2162C→T、2168A→G)及线粒体DNA12S rRNA(1494→T、1555A→G)。结果 139例耳聋患者中共检出41例存在致聋突变(29.49%)。GJB2基因突变24例(16.11%),其中235delC纯合突变10例,235delC单杂合突
16例,235delC/299-300delAT复合杂合突变8例;SLC26A4基因突变16例(11.51%),其中IVs7-2A→G纯合突变5例,IVs7-2A→G杂合突变4例,IVSl5+5G→A杂合突变2例,IVs7-2A→G/1229C→T复合杂合突变3例,2027T→A杂合突变2例;线粒体DNA12S rRNA基因同质突变1例(0.72%),位点为1555A→G。结论 GJB2基因突变是导致云南地区非综合征性聋患儿听力损失的主要原因,235delC是其最常见的突变形式,IVs7-2A→G为SLC26A4基因主要的突变形式。对本地区耳聋患者行常见基因的筛查,将为部分患儿和家庭提供分子病因学诊断和相应的遗传学咨询。 相似文献
13.
Yalin Ma Yun Xiao Xiaohui Bai Fengguo Zhang Daogong Zhang Xinmao Xu 《Acta oto-laryngologica》2016,136(8):800-805
Conclusion: In this cohort of 156 non-syndromic hearing-impaired subjects of Tengzhou area, the most common deafness-associated genes GJB2, SLC26A4 and mtDNA 12S rRNA were investigated by SNPscan efficiently. GJB2 c.235delC and SLC26A4 c.IVS7-2A?>?G were the most common mutation sites. Objectives: Until now, there is no systematic gentic analysis in patients with non-syndromic hearing loss for Tengzhou area, so we evaluated the molecular etiology to investigate the hot-sports. Methods: Peripheral blood samples were obtained from 156 patients with severe-to-profound non-syndromic deafness in Tengzhou. The SNP scan assay technique was performed for a rapid multiplex genetic screening to detect the 115 mutations of the most common three genes. All results were statistically analyzed with SPSS software. Results: Among the 156 analyzed patients, 60 patients were demonstrated with deafness genes, accounting for 38.46% (60/156), including GJB2 (22.44%, 35/156), SLC26A4 (13.66%, 22/156), and mtDNA 12S rRNA (2.56%, 4/156). In this study, we confirmed 23 deafness-causing mutations and 27 different allelic combinations including GJB2 (eight variants, 11 allelic combinations), SLC26A4 (13 variants, 16 allelic combinations) and mtDNA 12S rRNA (two variants). The occurrence rates of these deafness-causing mutations GJB2 c.235delC and SLC26A4 c.IVS7-2A?>?G were significantly higher than other mutation sites (p?0.01). 相似文献
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Bazazzadegan N Nikzat N Fattahi Z Nishimura C Meyer N Sahraian S Jamali P Babanejad M Kashef A Yazdan H Sabbagh Kermani F Taghdiri M Azadeh B Mojahedi F Khoshaeen A Habibi H Reyhanifar F Nouri N Smith RJ Kahrizi K Najmabadi H 《International journal of pediatric otorhinolaryngology》2012,76(8):1164-1174
16.
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
17.
语前聋患儿6岁前与6岁后植入人工耳蜗效果的比较 总被引:2,自引:0,他引:2
目的比较6岁前与6岁后两个年龄组语前聋患儿人工耳蜗植入术后的听觉言语康复的效果. 方法对31例语前聋人工耳蜗植入患儿,术后随访0.5~4年,按手术年龄分成A组(1.0~5.9岁)和B组(6.0~17.9岁),进行术后的听觉和言语识别率的评估. 结果 31例语前聋人工耳蜗植入患儿全部手术成功,全部建立了主观听性反应.A组的纯音听力水平平均为30dBSPL,开放式言语识别率平均为90%.B组的纯音听力水平平均为36dBSPL,开放式言语识别率平均为85%. 结论植入人工耳蜗的语前聋患儿1.0~5.9岁与6.0~17.9岁比较,在术后的言语识别率和语言清晰度两方面的听觉言语康复效果有显著性差异,年龄越小效果越好.因此,为达到满意的听觉言语康复效果,人工耳蜗植入的时机最好在6岁之前. 相似文献
18.
《International journal of audiology》2013,52(7):466-471
AbstractObjective: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients. Design: Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. Study sample: A cohort of 264 Portuguese NSSHL patients. Results: At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations. Conclusions: This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families. 相似文献
19.
目的研究中国散发耳聋患者与缝隙连接蛋白beta-6基因(gap junction protein beta 6 gene,GJB6)突变的相关性。方法分别设计扩增GJB6基因编码区和大片缺失后产物的引物各1对,应用PCR产物直接测序方法对各种感音神经性耳聋患者214例、正常听力者86例进行GJB6基因的突变检测及鉴定。结果没有发现在欧美耳聋人群中常见的GJB6大片段缺失,在214例患者中仅发现GJB6基因一种杂合错义突变,为一个新的突变形式233(C→A),进一步的各物种多种连接蛋白氨基酸序列进化分析证实该突变位点位于C×30高度保守的第二跨膜区。86例正常对照组中未发现同样突变。结论通过研究发现GJB6突变不是中国散发耳聋患者中的常见致病因素,为下一步开展耳聋相关基因和临床基因诊断研究打下了基础。 相似文献
20.
目的研究佛山地区先天性聋儿中GJB2突变和线粒体DNAA1555G突变在耳聋发病中的作用。方法收集180例散发的先天性聋儿的DNA,利用聚合酶链反应一限制性片断长度多态性(PCR—RFLP)方法和Prey—DAF药物性耳聋基因诊断试剂盒对收集到的DNA进行分析,筛查患者GJB2235deIC突变和线粒体DNAA1555G突变。结果经PCR-RFLP和Prev—DAF药物性耳聋基冈诊断试剂盒分析,在所有参加检测的180名患儿中共发现GJB2235delC纯合突变14名(7.78%),GJB2235delC杂和突变7名(3.89%),线粒体DNAA1555G突变6名(3.33%)。结论应用基因检测方法可以在地区性耳聋流行病学凋查中帮助明确常见的遗传性耳聋病例,并可指导此类患者的家庭进行耳聋的预防。 相似文献