Absence of GJB2 gene mutations, the GJB6 deletion (GJB6-D13S1830) and four common mitochondrial mutations in nonsyndromic genetic hearing loss in a South African population

Objective

The purpose of this study was to determine the prevalence of mutations in the GJB2 gene, the GJB6-D13S1830 deletion and the four common mitochondrial mutations (A1555G, A3243G, A7511C and A7445G) in a South African population.

Methods

Using single-strand conformation polymorphism and direct sequencing for screening GJB2 mutation; Multiplex PCR Amplification for GJB6-D13S1830 deletion and Restriction Fragment-Length Polymorphism (PCR-RFLP) analysis for the four common mtDNA mutations. We screened 182 hearing impaired students to determine the frequency of these mutations in the population.

Results

None of the reported disease causing mutations in GJB2 nor any novel pathogenic mutations in the coding region were detected, in contrast to the findings among Caucasians. The GJB6-D13S1830 deletion and the mitochondrial mutations were not observed in this group.

Conclusion

These results suggest that GJB2 may not be a significant deafness gene among sub-Saharan Africans, pointing to other unidentified genes as responsible for nonsyndromic hearing loss in these populations.     

Frequency of GJB2 and del(GJB6-D13S1830) mutations among an Ecuadorian mestizo population

Objective

The frequency of GJB2 mutations and of the del(GJB6-D13S1830) mutation has not been established among the Ecuadorian mestizo population diagnosed with autosomal recessive non-syndromic hearing loss. A genetic analysis was therefore designed in order to do so.

Methods

The sample population included 111 subjects of which 26 were autosomal recessive non-syndromic hearing loss probands. Posterior to PCR amplification, sequencing analysis of exon 2 was used for mutational detection of the GJB2 gene; a multiplex PCR method was used for detection of the del(GJB6-D13S1830) mutation. The ratio of subjects with a certain state of the mutation (heterozygous/homozygous) is expressed as a percentage and significant differences between probands and controls were calculated using Fisher's exact test; P < 0.05 was considered significant.

Results

A total of 104 mutations belonging to 8 allelic variations were identified. The most common being the V27I (58.9%); however, as this variation is a non-pathogenic polymorphism, Q7X, with a total of 19 mutated alleles, was the most frequent mutation (18.3%). The V27I polymorphism was the only variation distributed homogenously among probands and controls (P = 0.351). Based on physical analyses of multiple patients we confirm that Q7X causes a non-syndromic form of hearing loss and propose that it is a possible predominant mutation in the Ecuadorian population.

Conclusions

This is the first study of its kind among the Ecuadorian population and a preliminary step in establishing GJB2 and del(GJB6-D13S1830) mutational frequencies in this population; it is also the first to report of such a high frequency of the Q7X mutation. The data presented here brings Ecuador a step closer to providing more efficient treatment for a broader number of patients; additionally, it contributes to a better understanding of the relationship between autosomal recessive non-syndromic hearing loss and mutations on the GJB2 gene.     

Identification of both MT-RNR1 m.1555A>G and bi-allelic GJB2 mutations in probands with non-syndromic hearing loss

Objectives

Mutations in GJB2 and MT-RNR1 are common causes for non-syndromic sensorineural hearing loss (NSHL). In this study, we investigated the co-existence of both MT-RNR1 and bi-allelic GJB2 mutations in a large number of simplex and multiplex probands with NSHL.

Methods

485 simplex and 134 multiplex probands with NSHL were recruited for mutation screening of GJB2 and MT-RNR1 by bidirectional sequencing. Clinical features of probands with both MT-RNR1 and bi-allelic GJB2 mutations were further analyzed in comparison with extended family members.

Results

MT-RNR1m.1555A>G and bi-allelic GJB2 mutations were both detected in one (0.21%) simplex probands and two (1.49%) multiplex probands. Variable hearing phenotypes were found in a pair of siblings with both MT-RNR1 and bi-allelic GJB2 mutations.

Conclusion

MT-RNR1 and bi-allelic GJB2 mutations may co-exist not only in multiplex probands but also in simplex probands. The variable hearing phenotypes in closely-related family members may reflect the co-existence of different molecular causes and prompt extended genetic tests.     

Long term speech perception after cochlear implant in pediatric patients with GJB2 mutations

Objectives

To determine the long term effect of cochlear implant (CI) in children with GJB2-related deafness in Japan.

Methods

Genetic testing was performed on 29 children with CI. The speech perception in 9 children with GJB2 gene-related deafness fitted with CI was compared with those in matched 10 children who were diagnosed as having no genetic loci. The average follow-up period after CI was 55.9 months and 54.6 months, respectively.

Results

A definitive inherited hearing impairment could be confirmed in 12 (41.4%) of the 29 CI children, including 10 with GJB2-related hearing impairment and 2 with SLC26A4-related hearing impairment. The results of IT-MAIS, word or speech perception testing under the noise, and development of speech perception and production testing using the Enjoji scale were slightly better for the GJB2 group after CI than for the control group without statistical significant difference.

Conclusion

The long-term results of this study show that CI is also effective in the development of speech performance after CI in Japanese children with GJB2-related hearing impairments as HL due to other etiologies.     

GJB2 mutation spectrum in 209 hearing impaired individuals of predominantly Caribbean Hispanic and African descent

Objective

The purpose of the study is to determine whether Caribbean Hispanic and African admixture populations have a paucity of mutations in GJB2, encoding connexin 26.

Methods

We reported the paucity of mutations in GJB2 and deletions in GJB6 in Caribbean Hispanic and African admixture populations in the Bronx, NY, in 2007 [1]. We have now collected 102 additional probands with non-syndromic sensorineural hearing impairment (NSHI), for a total of 209. We describe here a presentation of the combined data.

Results

Of the 209 probands, 36% have affected family members with NSHI and the rest have sporadic occurrence. Of the familial cases, 43% had a first-degree relative affected, and the remainder a more distant relative. The hearing impairment ranged from unilateral mild to bilateral profound, with 76% exhibiting bilateral NSHI (BLNSHI). The single coding exon of the GJB2 gene was sequenced in 209 probands, PCR screening for del(GJB6-D13S1830) and sequencing of the non-coding exon of GJB2 to look for the known splice site mutation was performed in 32 NSHI patients with a heterozygous variation in GJB2, and multiplex ligation-dependent probe amplification (MLPA) testing of GJB2 and GJB6 exon deletions or amplifications (P163 GJB-WFS1 kit) was done in 70 probands. Eight unrelated individuals had biallelic GJB2 mutations, representing 4% of our entire cohort, or 5% of our probands with BLNSHI. Of 127 probands of Hispanic or African descent with BLNSHI, six (4.7%) had biallelic pathogenic mutations, three (2.3%) had monoallelic mutations and 118 (93%) had no disease-causing mutations in GJB2. At the same time, no major deletions were identified either by PCR screening (del(GJB6-D13S1830)) or by MLPA analysis (GJB2 or GJB6), and no subjects had the known splice site mutation in GJB2.

Conclusion

These results demonstrate that GJB2 is not the major contributor to the genetic basis of NSHI for the Bronx minority admixture populations.     

Prevalence of c.35delG and p.M34T mutations in the GJB2 gene in Estonia

Objective

The purpose of this study was to determine the prevalence of c.35delG and p.M34T mutations in the GJB2 gene among children with early onset hearing loss and within a general population of Estonia.

Methods

Using an arrayed primer extension assay, we screened 233 probands with early childhood onset hearing loss for 107 different mutations in the GJB2 gene. We then looked for the two most common mutations, c.35delG and p.M34T, in a population of 998 consecutively born Estonian neonates to determine the frequency of these mutations in the general population.

Results

In 115 (49%) of the patients with early onset hearing loss, we found a mutation in at least one allele of the GJB2 gene. Seventy-three (31%) were homozygous for the c.35delG mutation, seven (3%) were homozygous for the p.M34T mutation, and five (2%) had c35delG/p.M34T compound heterozygosity. Other six identified mutations in GJB2 gene occurred rarely. Among the 998 anonymous newborn samples, we detected 45 who were heterozygous for c.35delG, 2 individuals homozygous for c.35delG, and 58 who were heterozygous for p.M34T. Additionally, we detected two c.35delG/p.M34T compound heterozygotes.

Conclusion

The most common GJB2 gene mutations in Estonian children with early onset hearing loss were c.35delG and p.M34T, with c.35delG accounting for 75% of GJB2 alleles. The carrier frequency for c.35delG and p.M34T in a general population of Estonia was 1 in 22 and 1 in 17, respectively, and was higher than in most other countries.     

Prevalence of DFNB1 mutations in Argentinean children with non-syndromic deafness. Report of a novel mutation in GJB2

Objective

Mutations in DFNB1 locus, containing GJB2 (connexin 26) and GJB6 (connexin 30) genes, are the most common cause of autosomal recessive non-syndromic hearing loss. More than 100 mutations in GJB2 have been reported worldwide. Two deletions in GJB6, del(GJB6-D13S1830) and del(GJB6-D13S1854), have been found to be frequent in the Spanish population. The aim of this study was to determine the prevalence of GJB2 mutations and both GJB6 deletions in Argentinean children with non-syndromic deafness.

Methods

This study included 94 unrelated children with moderate to profound non-syndromic sensorineural hearing impairment. Molecular analysis was performed using a tiered approach. All DNA samples were screened for c.35delG mutation by PCR/RFLP. Samples from patients who were not homozygous for c.35delG were analysed for the presence of GJB6 deletions by PCR multiplex. The samples that remained unresolved after screening were further analysed by direct sequencing of GJB2 coding region. Finally, the splice site mutation IVS1 + 1G → A was analysed by PCR/RFLP.

Results

Sequence variations in the GJB2 and GJB6 genes were found in 49 of the 94 unrelated patients. The most prevalent GJB2 mutation, c.35delG, was found in 40 of the 68 pathogenic alleles with the second most common allele being p.R143W (4/68). Fourteen sequence variations other than c.35delG were identified. Seven already described mutations were present in more than one allele; among them, IVS1 + 1G → A, the rare splice site mutation flanking exon 1. In addition to known disease-related alterations, a novel GJB2 mutation, c.262G > C (p.A88P), was also identified. Six alleles were identified carrying GJB6 deletions; the most prevalent was del(GJB6-D13S1830). The frequency of the latter was found to be as high as that found in Spain from where Argentina has received one of its major immigration waves.

Conclusions

The overall frequency of GJB2/GJB6 mutations in the present sample is in agreement with other Caucasian populations. As expected, c.35delG was the most prevalent mutation. The deletion del(GJB6-D13S1830) was the second most common mutation. These findings reinforce the importance of the study of GJB2/GJB6 genes in diagnosis to provide early treatment and genetic counselling.     

A novel frameshift mutation (c.405delC) in the GJB2 gene associated with autosomal recessive hearing loss in two Tunisian families

Objectives

Mutations in GJB2 are found to be responsible for 50% of congenital autosomal recessive non-syndromic hearing loss, one of the most important mutations in this gene is the c.35delG, which is responsible for the majority of GJB2 related deafness in the Tunisian population. The aim of this study was to determine the molecular etiology of hearing loss in two Tunisian individuals.

Methods

We screened two Tunisian individuals affected by congenital, bilateral, profound, sensorineural hearing loss for mutations in GJB2 gene using PCR and direct sequencing.

Results

We identified a novel frameshift mutation in the GJB2 gene, the c.405delC resulting in a truncated protein (p.Tyr136Thrfs*32). It was found in compound heterozygosity with the c.35delG in two non-consanguineous unrelated families from Tunisia. One patient underwent a cochlear implant at 4 years. Initial evaluations post-implantation indicate a successful cochlear implant outcome since the patient began to acquire language abilities and auditory sensation.

Conclusions

With this novel GJB2 mutation, the mutational spectrum of this gene continues to broaden in our population. The occurrence of biallelic GJB2 mutations for the other deaf girl, despite the neonatal pain and hypotension due to complicated delivery, led us to confirm the importance of GJB2 screening for cochlear implant candidates regardless of the etiology of deafness in populations with a relatively high frequency of GJB2 mutation carriers.     

Compound heterozygosity for dominant and recessive GJB2 mutations in a Tunisian family and association with successful cochlear implant outcome

Objectives

Mutations of GJB2 encoding connexin 26 are the most common cause of hearing loss. They are responsible for up to 50% of ARNSHL. The pathogenic mutations in this gene are generally inherited recessively. Dominant mutations in GJB2 also cause hearing loss, either in isolated non-syndromic form or as part of a syndrome associated with various skin disorders.

Methods

We screened a Tunisian child affected by congenital, bilateral, profound, sensorineural hearing loss for mutations in GJB2 gene using PCR and direct sequencing.

Results

The proband was found to be compound heterozygous for recessive and dominant GJB2 mutations respectively p.V37I (c.109G > A) and p.R143Q (c.428G > A). Surprisingly the hearing mother is a carrier for this dominant GJB2 mutation. This proband underwent a cochlear implant at four years old. The evaluation using APCEI and IT-MAIS tests at six months post implantation indicates a successful cochlear implant outcome since the deaf child began to acquire language abilities and auditory sensation.

Conclusions

The p.R143Q mutation was described for the first time in Tunisia. We confirm the low penetrance of this mutation since the proband mother is a carrier despite her normal hearing. We show the effectiveness of cochlear implant to restore the communication abilities and auditory sensation for our patient.     

Newborn dried blood-spot screening of the p.V37I variant of GJB2 by high-resolution melting analysis

Objectives

To establish a high-throughput, low-cost method for neonatal genetic testing of the p.V37I of GJB2 gene, which is highly prevalent in East Asians and strongly associated with postnatal childhood hearing impairment.

Methods

A total of 6460 newborn blood-spot DNA samples were screened by high-resolution melting analysis (HRMA).

Results

The screening results were further verified by direct sequencing of 28 homozygous, 545 heterozygous and 200 wild-type samples.

Conclusion

Our study indicated that the HRMA-based bloodspot screening method was of very high sensitivity and specificity and was suitable for large-scale screening of the p.V37I variants in newborns.     

新疆哈萨克族非综合征型聋GJB2基因突变的研究分析

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。     

儿童双耳感音神经性聋临床特点及GJB2与GJB3基因突变分析

目的 探究并分析儿童双耳感音神经性聋临床表现特点及缝隙连接蛋白26（GJB2）、缝隙连接蛋白31（GJB3）基因突变情况。方法 本研究选取2020年3月—2021年3月接受治疗的150例双耳感音神经性聋患儿作为研究对象,纳入研究组;选择同期参与体检的150例听力正常的儿童作为对照组。试剂盒法提取血液白细胞中的基因组DNA,GJB2、GJB3基因采用编码区聚合酶链反应（PCR）进行检测。观察两组儿童GJB2和GJB3基因检测结果及研究组儿童耳聋程度、不同程度双耳感音神经性聋儿童的GJB2和GJB3耳聋基因突变率及基因突变位点情况、研究组儿童双亲GJB2、GJB3基因突变情况。结果 研究组儿童GJB2基因突变共50例（33.33%）,基因致病突变5种（35insG、95G>A、176-191del16、235delC、257C>G）,40例与235delC突变相关,占比80.00%;多态性基因改变3种（79G>A、341A>G、427C>T）;GJB3基因突变共6例（538C→T、547G→A）。对照组儿童GJB2基因突变共计3例（2.00%）,基因致病突变有两种（95G>A、235delC）;多态性基因改变有两种（79G>A、341A>G）;未发现GJB3基因突变。研究组儿童235delC突变率显著高于对照组（P<0.05）;研究组儿童中重度及极重度患者占达到59.33%（89/150）;不同程度双耳感音神经性聋儿童GJB2、GJB3基因突变率中极重度阳性检出率较高,分别为33.33%和7.5%;重度和危重度患儿致病突变位点例数显著高于轻中度患儿,多态性改变例数低于轻中度患儿（P均<0.05）。研究组儿童父母中发现GJB2基因突变父亲17例（5.67%）、母亲25例（8.33%）;GJB3基因突变父亲3例（1.00%）,母亲1例（0.33%）;父母亲均未检验出纯合突变和复合杂交突变以及GJB3基因突变。结论 目前临床暂无对双耳感音神经性聋的有效预防和诊断手段,而GJB2、GJB3基因突变检测可以作为产妇产前诊断的一种方法,从而对下一代进行预防,利于有效诊断耳聋的发生率,从而做到尽早预防,降低发病率。     

新疆维吾尔族非综合征性遗传性聋GJB2基因突变的研究

目的:研究新疆维吾尔族非综合征性遗传性聋患者GJB2基因突变的情况.方法:采用直接测序法对新疆维吾尔族非综合征性遗传性聋患者43例和健康对照46例进行GJB2基因突变的检测.结果:在编码区耳聋组共发现6种碱基改变:380G>A、109G>A、235 delC、233delC、71G>A及35 delG,其中235 delC杂合突变1例,233 delC纯合突变2例,35 delG杂合突变2例;对照组发现6种碱基改变,其中5种为已明确的常见多态性改变.结论:新疆维吾尔族非综合征性遗传性聋患者GJB2基因突变检出率较低,具有种族和地域性特点.     

GJB2 (connexin 26) gene mutations in Moroccan patients with autosomal recessive non-syndromic hearing loss and carrier frequency of the common GJB2-35delG mutation

OBJECTIVE: Mutations in the connexin 26 gene (GJB2), which encodes a gap-junction protein expressed in the inner ear, have been shown to be responsible for a major part of autosomal recessive non-syndromic hearing loss in Caucasians. The aim of our study was to determine the prevalence and spectrum of GJB2 mutations, including the (GJB6-D13S1830) deletion, in Moroccan patients and estimate the carrier frequency of the 35delG mutation in the general population. METHODS: Genomic DNA was isolated from 81 unrelated Moroccan familial cases with moderate to profound autosomal recessive non-syndromic hearing loss and 113 Moroccan control individuals. Molecular studies were performed using PCR-Mediated Site Directed Mutagenesis assay, PCR and direct sequencing to screen for GJB2, 35delG and del(GJB6-D13S1830) mutations. RESULTS: GJB2 mutations were found in 43.20% of the deaf patients. Among these patients 35.80% were 35delG/35delG homozygous, 2.47% were 35delG/wt heterozygous, 3.70% were V37I/wt heterozygous, and 1 patient was E47X/35delG compound heterozygous. None of the patients with one or no GJB2 mutation displayed the common (GJB6-D13S1830) deletion. We found also that the carrier frequency of GJB2-35delG in the normal Moroccan population is 2.65%. CONCLUSIONS: These findings indicate that the GJB2-35delG mutation is the major cause of autosomal recessive non-syndromic hearing loss in Moroccan population. Two other mutations were also detected (V37I and E47X), in agreement with similar studies in other populations showing heterogeneity in the frequencies and types of mutation in connexin 26 gene.     

Spectrum of GJB2 (Cx26) gene mutations in Iranian Azeri patients with nonsyndromic autosomal recessive hearing loss

Objective

Hereditary hearing impairment is a genetically heterogeneous disorder. In spite of this, mutations in the GJB2 gene, encoding connexin 26 (Cx26), are a major cause of nonsyndromic recessive hearing loss in many countries and are largely dependent on ethnic groups. The purpose of our study was to characterize the type and prevalence of GJB2 mutations among Azeri population of Iran.

Methods

Fifty families presenting autosomal recessive nonsyndromic hearing loss from Ardabil province of Iran were studied for mutations in GJB2 gene. All DNA samples were screened for c.35delG mutation by ARMS PCR. Samples from patients who were normal for c.35delG were analyzed for the other variations in GJB2 by direct sequencing. In the absence of mutation detection, GJB6 was screened for the del(GJB6-D13S1830) and del(GJB6-D13S1854).

Result

Thirteen families demonstrated alteration in the Cx26 (26%). The 35delG mutation was the most common one, accounting for 69.2% (9 out of 13 families). All the detected families were homozygous for this mutation. Two families were homozygous for delE120 and 299-300delAT mutations. We also identified a novel mutation: c.463-464 delTA in 2 families resulting in a frame shift mutation.

Conclusion

Our results suggest that c.35delG mutation in the GJB2 gene is the most important cause of GJB2 related deafness in Iranian Azeri population.     

Absence of GJB6 mutations in Indian patients with non-syndromic hearing loss

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.     

Hearing loss associated with an unusual mutation combination in the gap junction beta 2 (GJB2) gene in a Chinese family

Objective

To assess the molecular etiology of nonsyndromic sensorineural hearing loss (NSHL) in members of an affected Chinese family.

Methods

Common hearing-related genes including gap junction beta 2 (GJB2), SLC26A4, mitochondrial DNA 12S rRNA, GJB3 and GJB6 were examined in a family consisting of a normal hearing father, an NSHL-affected mother, one normal-hearing child and three NSHL-affected children. Specific primers were used in polymerase chain reactions to amplify the coding regions of the above genes from the peripheral blood DNA from each family member, and the genes were analyzed by direct sequencing. The subjects were evaluated for phenotypic characterization using audiometric testing and radiological examination of the inner ear.

Results

Pathogenic mutations in the GJB2 gene were identified. The affected mother showed a heterozygous G → A transition at nucleotide 232, resulting in an alanine to threonine substitution at codon 78 (p.A78T), and the normal hearing father had a c.35insG insertion mutation. The three affected children displayed heterozygosity for the GJB2 mutations, showing a previously unreported combination of c.35insG and c.232G>A.

Conclusions

The GJB2 mutations account for a significant proportion of NSHL in affected individuals worldwide. Genetic and audiological data analysis of a Chinese family with NSHL revealed a novel c.35insG/c.232G>A compound heterozygous state. Our results highlight the complexity of the GJB2 genotypes and phenotypes.     

Prevalence of GJB6 mutations in Chinese patients with non-syndromic hearing loss

Objective

To investigate the distribution of GJB6 mutations in Central Chinese population with non-syndromic hearing loss.

Method

Totally 655 hearing impaired patients in Hubei province of China were screened for del(GJB6-D13S1830) deletions by using multiplex PCR and sequencing of GJB6 whole coding region.

Result

The del(GJB6-D13S1830) and other mutations in GJB6 gene were not observed in our study cohort.

Conclusion

The results suggest that GJB6 mutations is not a common cause among Central Chinese population and screening for the mutations of GJB6 can be ranked as unconventional deaf gene test for this population.     

散发性耳聋GJB2基因突变分析

目的 通过分析内蒙古鄂尔多斯和呼和浩特地区散发性耳聋患者GJB2 235delC点突变,以探讨散发性耳聋患者的分子病因学。方法 对131例(汉族92例,蒙古族39例) 散发性耳聋患者进行耳聋病因学问卷调查、纯音听阈及声导抗测试。聚合酶链反应(polymerase chain reaction PCR)扩增目的片段并用限制性内切酶对其进行GJB2 235delC基因突变检测,对酶切检测结果呈阳性的样本用直接测序法进行验证。对50例健康中国人和100例健康加拿大白种人行限制性内切酶GJB2 235delC点突变检测,作为阴性对照。结果 131例散发性耳聋患者全部为感音神经性聋。在该群体中4例(汉族3例,蒙古族1例)存在GJB2 235delC纯合性突变;3例(汉族2例,蒙古族1例)存在GJB2 235delC杂合性突变。50例健康中国人对照组中检测出1例GJB2 235delC点突变携带者,100例健康加拿大白种人中未检测到GJB2 235delC点突变。结论 GJB2 235delC点突变是中国人散发性感音神经性耳聋的分子病因学之一。内蒙古地区汉族、蒙古族GJB2 235delC突变频率无明显差异,对GJB2 235delC点突变的基因筛查可以明确一些散发性耳聋患者的病因,从而对基因突变引起的散发性耳聋的早期诊断、遗传咨询及防聋治聋起到重要作用。