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GJB2 Gene (gjb2 + gene)
Selected AbstractsAbsence of deafness-associated connexin-26 (GJB2) gene mutations in the Omani population ,,HUMAN MUTATION, Issue 6 2001Mehmet Simsek Abstract We have investigated the prevalence of mutations in the connexin 26 (GJB2) gene in Omani population using both PCR-RFLP and direct DNA sequencing methods. Two common GJB2 gene mutations (35delG and 167delT) were screened in 280 healthy controls and 95 deaf patients using two different PCR-RFLP methods. To investigate other GJB2 mutations, we have amplified and sequenced DNA from 51 unrelated deaf patients and 17 control subjects. None of the samples studied, either by RFLP or sequencing, revealed any deafness-associated mutations in the coding region of the GJB2 gene. These findings disagree with many reports on the GJB2 gene, describing various mutations as the cause of congenital recessive deafness. Although, an amino acid substitution (S86T) was identified by sequencing, we conclude that this change could not be associated with deafness since it was present in all the control and patient samples sequenced. © 2001 Wiley-Liss, Inc. [source] First report of prenatal diagnosis of genetic congenital deafness in a routine prenatal genetic testPRENATAL DIAGNOSIS, Issue 13 2003M. L. Santoro Abstract Objective We aimed to screen for connexin26 gene (GJB2) mutations associated with autosomal recessive non-syndromic neurosensory deafness (NSRD) in a general risk population. Methods Screening for the most common connexin26 gene mutations was offered to all women undergoing a second-trimester amniocentesis for fetal karyotype analysis in our Center. After rapid DNA extraction from amniotic fluid, PCR amplification was performed and products analysed to detect mutations of GJB2 gene by a sequencing technique. In particular, we searched for the 20 most frequently reported mutations (out of the approximately 90 so far described) and for which there are commercially available tests. Results From a total of 4819 consecutive amniotic fluids examined, the following five different heterozygous mutations were detected: 35delG in 80 cases, 167delT in 3 cases and 1 occurrence of each of the following mutations: M34T, 35insG and W77R. From these data, a prevalence of 1 : 56 (1.78%) for the heterozygous condition can be estimated in the Mediterranean general risk population. The striking predominance of 35delG mutation is confirmed. In addition, we detected a homozygous 35delG mutation condition in a foetus of no risk parents. In this case, the early diagnosis permitted prompt application of an acoustic prosthesis allowing for cochlear implantation in due time, with significant improvement of the prognosis. Conclusions In a general risk population, a carrier status for congenital deafness can be observed in 1 : 56 (1.78%) amniotic fluids; this is mostly due to the presence of a 35delG mutation of the connexin26 gene. Occasional identification of homozygous states, although rare, allows the best therapeutic approach. Copyright © 2003 John Wiley & Sons, Ltd. [source] A New De Novo Missense Mutation in Connexin 26 in a Sporadic Case of Nonsyndromic DeafnessTHE LARYNGOSCOPE, Issue 5 2007Paola Primignani PhD Abstract Objectives: Mutations in the GJB2 gene, encoding Connexin 26, can cause nonsyndromic recessive deafness or dominant hearing loss (HL) with or without keratoderma. The objective was to perform a molecular evaluation to establish the inherited pattern of deafness in the sporadic cases afferent to our center. Methods: The subject was a 2-year-old Italian girl with nonsyndromic early onset HL. We performed DNA sequencing of the GJB2 gene and deletion analysis of the GJB6 gene in all family members. Results: Direct sequencing of the gene showed a heterozygous C,G transition at nucleotide 172 resulting in a proline to alanine amino acid substitution at codon 58 (P58A). The analyses indicate that the P58A mutation appeared de novo in the proband with a possible dominant effect. Conclusions: This mutation occurs in the first extracellular domain (EC1), which seems to be very important for connexon-connexon interaction and for the control of voltage gating of the channel. The de novo occurrence of an EC1 mutation in a sporadic case of deafness is consistent with the assumption that P58A can cause dominant HL. [source] GJB2 Mutations in Mongolia: Complex Alleles, Low Frequency, and Reduced Fitness of the DeafANNALS OF HUMAN GENETICS, Issue 2 2010Mustafa Tekin SUMMARY We screened the GJB2 gene for mutations in 534 (108 multiplex and 426 simplex) probands with non-syndromic sensorineural deafness, who were ascertained through the only residential school for the deaf in Mongolia, and in 217 hearing controls. Twenty different alleles, including four novel changes, were identified. Biallelic GJB2 mutations were found in 4.5% of the deaf probands (8.3% in multiplex, 3.5% in simplex). The most common mutations were c.IVS1 + 1G > A (c.-3201G > A) and c.235delC with allele frequencies of 3.5% and 1.5%, respectively. The c.IVS1 + 1G > A mutation appears to have diverse origins based on associated multiple haplotypes. The p.V27I and p.E114G variants were frequently detected in both deaf probands and hearing controls. The p.E114G variant was always in cis with the p.V27I variant. Although in vitro experiments using Xenopus oocytes have suggested that p.[V27I;E114G] disturbs the gap junction function of Cx26, the equal distribution of this complex allele in both deaf probands and hearing controls makes it a less likely cause of profound congenital deafness. We found a lower frequency of assortative mating (37.5%) and decreased genetic fitness (62%) of the deaf in Mongolia as compared to the western populations, which provides an explanation for lower frequency of GJB2 deafness in Mongolia. [source] Double Heterozygosity with Mutations Involving both the GJB2 and GJB6 Genes is a Possible, but very Rare, Cause of Congenital Deafness in the Czech PopulationANNALS OF HUMAN GENETICS, Issue 1 2005P. Seeman Summary Mutations in the GJB2 gene are the most common cause of prelingual, autosomal recessive, sensorineural hearing loss worldwide. Nevertheless, 10% to 50% of patients with prelingual nonsyndromic deafness only carry one mutation in the GJB2 gene. Recently a large 342 kb deletion named ,(GJB6-D13S1830) involving the GJB6 gene was reported in Spanish and French deafness patients, either in a homozygous state or in combination with a monoallelic GJB2 mutation. No data have been reported about the frequency of this mutation in central Europe. Thirteen Czech patients with prelingual nonsyndromic sensorineural deafness carrying only one pathogenic mutation in the GJB2 gene were tested for the presence of the ,(GJB6-D13S1830) mutation. One patient with a GJB2 mutation (313del14) also carried the ,(GJB6-D13S1830). This is the first reported Czech case, and probably also the first central European case, of prelingual deafness due to mutations involving both the GJB2 and GJB6 genes. In addition, the ,(GJB6-D13S1830) was not detected in 600 control chromosomes from Czech individuals with normal hearing. We show that in the Czech Republic the ,(GJB6-D13S1830) is not the second most common causal factor in deafness patients heterozygous for a single GJB2 mutation, and that ,(GJB6-D13S1830) is very rare in central Europe compared to reports from Spain, France and Israel. [source] Germline mosaicism in keratitis,ichthyosis,deafness syndrome: pre-natal diagnosis in a familial lethal formCLINICAL GENETICS, Issue 6 2010E Sbidian Sbidian E, Feldmann D, Bengoa J, Fraitag S, Abadie V, de Prost Y, Bodemer C, Hadj-Rabia S. Germline mosaicism in keratitis,ichthyosis,deafness syndrome: pre-natal diagnosis in a familial lethal form. Keratitis,ichthyosis,deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin-26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre-natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non-consanguineous healthy parents lead to perform pre-natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin. [source] Causes of deafness in British Bangladeshi children: a prevalence twice that of the UK population cannot be accounted for by consanguinity aloneCLINICAL OTOLARYNGOLOGY, Issue 2 2009Y. Bajaj Objective:, To study the causes and prevalence of sensorineural deafness in Bangladeshi children resident in East London. Methods:, This was a cross sectional survey of children of Bangladeshi origin living in East London with bilateral sensorineural hearing loss of 40 db HL or more. In this study, 134 patients were included. The study looked primarily at the causes of sensorineural hearing loss in this population. Results:, The prevalence of deafness in Bangladeshi children in East London is approximately 3.86 per 1000 [95% confidence intervals (CI) 3.20, 4.65] which is significantly greater than the average UK prevalence of 1.65 per 1000. The prevalence of deafness in these Bangladeshi children belonging to non-consanguineous families only, the prevalence falls to 2.73 per 1000 (95% CI 2.19, 3.41). In 60% cases the cause of deafness was genetic. The single most common cause of sensorineural hearing loss in this population was mutations in the GJB2 gene (Connexin 26) in 20 of these patients (17%). Parents were consanguineous in 33% of the families. Conclusion:, This study concludes that prevalence of sensorineural deafness in Bangladeshi children is at least 2.3 times the national average. This study also concludes that genetic causes are the common cause of deafness in this ethnic group, with nearly 30% of children with non-syndromic deafness having mutations in GJB2. Although parental consanguinity was very high in this population it did not account for the whole increase in prevalence. [source] | |||||||||||||