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1.
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
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.
Luciana Santos Serrão de Castro Anderson Nonato do Rosario Marinho Elzemar Martins Ribeiro Rodrigues Giorgio Christie Tavares Marques Tarcísio André Amorim de Carvalho Luiz Carlos Santana da Silva Sidney Emanuel Batista dos Santos 《Revista brasileira de otorrinolaringologia (English ed.)》2013,79(1):95-99
Hearing impairment affects about 1 in 1000 newborns. Mutations in the connexin 26 (GJB2) gene rank among the most frequent causes of non-syndromic deafness in different populations, while delGJB6-D13S1830 mutation located in the DFNB30 locus is known to cause sensorineural hearing loss. Despite the many studies on the involvement of GJB2 mutations in hearing impairment in different populations, there is little information on genetic deafness in Brazil, especially in the Amazon region.ObjectiveTo determine the prevalence of GJB2 mutations and delGJB6-D13S1830 in 77 sporadic non-syndromic deaf patients.MethodThe coding region of the GJB2 gene was sequenced and polymerase chain reaction was performed to detect the delGJB6-D13S1830 mutation.ResultsMutant allele 35delG was found in 9% of the patients (7/77). Mutations M34T and V95M were detected in two distinct heterozygous patients. Non-pathogenic mutation V27I was detected in 28.6% of the patients (22/77). None of the deaf patients carried the delGJB6-D13S1830 mutation.ConclusionMutant alleles on gene GJB2 were observed in 40% (31/77) of the subjects in the sample. Pathogenic variants were detected in only 12% (9/77) of the individuals. More studies are required to elucidate the genetic causes of hearing loss in miscegenated populations. 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.
Chen P Chen H Fu S Chen G Dong J 《International journal of pediatric otorhinolaryngology》2012,76(2):265-267
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. 相似文献7.
8.
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9.
César Paz-y-Miño Doyle Beaty Andrés López-Cortés Indira Proaño 《International journal of pediatric otorhinolaryngology》2014
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. 相似文献10.
11.
Hearing impairment in Dutch patients with connexin 26 (GJB2) and connexin 30 (GJB6) mutations 总被引:1,自引:0,他引:1
Santos RL Aulchenko YS Huygen PL van der Donk KP de Wijs IJ Kemperman MH Admiraal RJ Kremer H Hoefsloot LH Cremers CW 《International journal of pediatric otorhinolaryngology》2005,69(2):165-174
OBJECTIVE: Despite the identification of mutations in the connexin 26 (GJB2) gene as the most common cause of recessive nonsyndromic hearing loss, the pattern of hearing impairment with these mutations remains inconsistent. Recently a deletion encompassing the GJB6 gene was identified and hypothesized to also contribute to hearing loss. We hereby describe the hearing impairment in Dutch patients with biallelic connexin 26 (GJB2) and GJB2+connexin 30 (GJB6) mutations. METHODS: The audiograms of patients who were screened for GJB2 and GJB6 mutations were analysed retrospectively. Standard statistical testing was done for symmetry and shape, while repeated measurement analysis was used to assess the relation between mutation and severity. Progression was also studied via linear regression analysis. RESULTS: Of 222 hearing-impaired individuals, 35 exhibited sequence variations; of these 19 had audiograms for study. Hearing loss in patients with biallelic "radical" (i.e. deletions, nonsense and splice site) mutations was significantly worse than in the wild type and heterozygotes (SAS proc GENMOD, p=0.013). The presence of at least one missense mutation in compound heterozygotes tends to lead to better hearing thresholds compared to biallelic radical mutations (p=0.08). One patient with the [35delG]+[del(GJB6-D13S1830)] genotype was severely impaired. Non-progressive hearing impairment was demonstrated in five 35delG homozygotes in individual longitudinal analyses. However a patient with the [299A>C]+[416G>A] genotype showed significant threshold progression in the lower frequencies. Findings on asymmetry and shape were inconclusive. CONCLUSIONS: Our data support the hypothesis that severity is a function of genotype and its effect on the amino acid sequence. A bigger cohort is required to establish non-progressivity more definitively. 相似文献
12.
13.
Longitudinal phenotypic analysis in patients with connexin 26 (GJB2) (DFNB1) and connexin 30 (GJB6) mutations 总被引:2,自引:0,他引:2
Stinckens C Kremer H van Wijk E Hoefsloot LH Huygen PL Standaert L Fryns JP Cremers CW 《The Annals of otology, rhinology, and laryngology》2004,113(7):587-593
In 15 Belgian subjects with prelingual sensorineural hearing impairment, the connexin 26 (GJB2) gene and the connexin 30 (GJB6) gene were analyzed for the presence of the 35delG mutation and the delta(GJB6-D13S1830) deletion first described by del Castillo et al in 2002. Seven patients were found to be homozygous for the 35delG mutation; 7 were combined heterozygotes for the 35delG mutation and the GJB6 deletion. In 11 subjects, phenotype and genotype were correlated. Significant, transient progression, in the range of 1.7 to 2.7 dB/y, was only found in 2 patients in the first part of the second decade of life. Hearing impairment was otherwise stable, with mean thresholds of 75, 90, and 100 dB at 0.125, 0.25, and 0.5 kHz, respectively, and 100 dB or higher at 1 to 4 kHz. There was no significant difference in hearing impairment between the patients with the homozygous 35delG mutation in GJB2 and those who are heterozygous for both the 35delG mutation and the deletion encompassing part of GJB6. 相似文献
14.
Abidi O Boulouiz R Nahili H Ridal M Alami MN Tlili A Rouba H Masmoudi S Chafik A Hassar M Barakat A 《International journal of pediatric otorhinolaryngology》2007,71(8):1239-1245
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. 相似文献
15.
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16.
17.
Maria Carolina Braga Norte Esteves Myriam de Lima Isaac Anete Maria Francisco Wilson Araújo da Silva Junior Cristiane Ayres Ferreira Ana Helena Banwart Dell’Aringa 《European archives of oto-rhino-laryngology》2014,271(4):695-699
Mutations in the GJB2 gene, mainly 35delG, are responsible for most autosomal recessive inherited genetic hearing loss. The audiometric standard of these hearing losses remains inconsistent and other genes, such as GJB6, have been involved in association with GJB2. The objective of the study was to identify the deletions del(GJB6-D13S1830) and del(GJB6-D13S1854) in patients heterozygous for 35delG/GJB2 and analyze the phenotype they present. 101 patients with mild to profound degree of sensorineural hypoacusis were evaluated. The allele-specific PCR technique was used to identify 35delG. The del(GJB6-D13S1830) and del(GJB6-D13S1854) were identified through the PCR multiplex technique. 90 % of the subjects presented a normal genotype for the analyzed mutations; 6.93 % were shown to be heterozygous for 35delG/GJB2 and 1 % presented compound heterozygosis GJB2/GJB6). The data found reinforced the hypothesis of an interaction of more than one gene as the cause of autosomal recessive genetic hearing loss and emphasized the importance of an early diagnosis for appropriate intervention. 相似文献
18.
Marlin S Feldmann D Blons H Loundon N Rouillon I Albert S Chauvin P Garabédian EN Couderc R Odent S Joannard A Schmerber S Delobel B Leman J Journel H Catros H Lemarechal C Dollfus H Eliot MM Delaunoy JL David A Calais C Drouin-Garraud V Obstoy MF Goizet C Duriez F Fellmann F Hélias J Vigneron J Montaut B Matin-Coignard D Faivre L Baumann C Lewin P Petit C Denoyelle F 《Archives of otolaryngology--head & neck surgery》2005,131(6):481-487
19.
20.
Pampanos A Economides J Iliadou V Neou P Leotsakos P Voyiatzis N Eleftheriades N Tsakanikos M Antoniadi T Hatzaki A Konstantopoulou I Yannoukakos D Gronskov K Brondum-Nielsen K Grigoriadou M Gyftodimou J Iliades T Skevas A Petersen MB 《International journal of pediatric otorhinolaryngology》2002,65(2):101-108
OBJECTIVE: Mutations in the gene encoding the gap junction protein connexin 26 (GJB2) have been shown as a major contributor to prelingual, sensorineural, nonsyndromic, recessive deafness. One specific mutation, 35delG, has accounted for the majority of the mutations detected in the GJB2 gene in Caucasian populations. The aim of our study was to determine the prevalence and spectrum of GJB2 mutations in prelingual deafness in the Greek population. METHODS: In a collaboration with the major referral centers for childhood deafness in Greece, patients were examined by an extensive questionnaire to exclude syndromic forms and environmental causes of deafness and by allele-specific polymerase chain reaction (PCR) for the detection of the 35delG mutation. Patients heterozygous for the 35delG mutation were further analyzed by direct genomic sequencing of the coding region of the GJB2 gene. RESULTS: The 35delG mutation was found in 42.2% of the chromosomes in 45 familial cases of prelingual, nonsyndromic deafness (18 homozygotes and 2 heterozygotes) and in 30.6% of the chromosomes in 165 sporadic cases (45 homozygotes and 11 heterozygotes). Direct genomic sequencing in heterozygous patients revealed the L90P (2 alleles), W24X (2 alleles), R184P (2 alleles), and 291insA (1 allele) mutations. CONCLUSION: Mutations in the GJB2 gene are responsible for about one third of prelingual, sensorineural, nonsyndromic deafness in the Greek population, and allele-specific PCR is an easy screening method for the common 35delG mutation. 相似文献