Coding Region Of GJB2 Gene Research Articles

GJB2 as Well as SLC26A4 Gene Mutations are Prominent Causes for Congenital Deafness.

Mutations in gap junction proteins encoding beta connexions are believed to be a major cause for congenital hearing loss. The purpose of this study was to do comparative analyses of frequencies of most prominent mutations responsible for congenital deafness. Using fluorescence PCR method, the entire coding region of GJB2 gene, GJB3 gene, and SLC26A4 was analyzed. Direct DNA sequencing was used to analyze mutations in these genes among unrelated 2,674 cases of newborns. Also, 12S rRNA mutation was also studied in these cases. In 2,674 cases of newborns from June 2013 to June 2014, found deafness mutation in 137 cases (5.12% of carrier rate), carrying GJB2 mutations in 68 cases (2.54% of carry rate), GJB3 mutations in 10 cases (0.37% of carry rate), SLC26A4 mutations in 54 cases (2.02% of carry rate), and mitochondrial 12S rRNA mutations in five cases (0.19% of carry rate). The study concludes that GJB2 gene mutation is the most common and mitochondrial 12S rRNA mutations are the least common mutation for congenital hearing loss in Chinese newborns.

A Novel Mutation in the GJB2 (Connexin 26) Gene in Egyptian Children with Non-syndromic Sensorineural Hearing Loss

This study aimed to investigate the frequency of any novel gene mutations, in human GJB2 gene among Egyptians with familial sensorineural non-syndromic hearing impairment. PCR amplifying the entire coding region of GJB2 gene and direct DNA sequencing to analyze mutations in this gene among 78 cases with autosomal recessive congenital non syndromic hearing loss was used. We describe for the first time a novel mutation in the coding region of the GJB2 gene. A deletion mutation of T at position 59, in the intracellular domain of connexin 26, resulting in a frameshift at the 20 th amino acid leading to a premature termination of the protein was detected in 9% of the studied cases. These data provide a novel molecular explanation for the role of GJB2 mutation in hearing loss to be taken into consideration in the genetic diagnosis and counseling of non-syndromic sensorineural hearing loss in Egyptians.

Mutation detection in GJB2 gene among Malays with non-syndromic hearing loss

ObjectivesTo identify the mutations in the GJB2 gene and to determine its association with non-syndromic hearing loss in Malays. MethodsA comparative cross sectional study was conducted on a group of children from the deaf schools and the normal schools. A total of 91 buccal cell samples of non-syndromic hearing loss and 91 normal hearing children were taken. Polymerase chain reaction was used to amplify the coding region of GJB2 gene. The PCR product of GJB2 coding region was preceded with screening for mutations using denaturing high performance liquid chromatography (dHPLC) and mutations detected were confirmed by DNA sequencing. ResultsTwelve sequence variations including mutations and polymorphisms were found in 32 patients and 37 control subjects. The variations were G4D, V27I, E114G, T123N, V37I and R127H in both groups, W24X, R32H, 257_259 del CGC and M34L in patients only and I203T and V153I in control subjects only. There were no association between homozygous (P=0.368) or heterozygous (P=0.164) GJB2 gene and non-syndromic hearing loss. ConclusionsThe types of GJB2 gene mutation were different and vary in Malay non-syndromic hearing loss as compared to the other races. Furthermore, the mutation did not associate with hearing loss in the population. Other related genes are believed to be involved and need to be sought in this group of patients.

The clinical features of patients with the homozygous 235delC and the compound-heterozygous Y136X/G45E of the GJB2 mutations (Connexin 26) in cochlear implant recipients

This study aimed to investigate the prevalence of GJB2 gene for the 235delC mutations, the clinical features and the outcomes of patients who had undergone cochlear implantation. We have sequenced the coding region of GJB2 gene for 135 patients with sensorineural deaf from September 2000 to May 2009. Of the 135 patients, the patients with the homozygous 235delC and the compound-heterozygous Y136X/G45E were detected and were investigated clinically. The GJB2 gene for the 235delC mutations was found in 39 alleles of 270 alleles (14.4%), especially for the homozygous of 235delC was detected in 26 alleles (9.6%), the single heterozygous of 235delC was 1 allele (0.4%), the compound heterozygous of 235delC was found in 12 alleles (4.4%). Of 16 subjects (29 alleles) with the homozygous 235delC and the compound-heterozygous Y136X/G45E, 2 subjects (4 alleles) were found to have complications. All of the subjects were found to show severe hearing loss and some of them have indicated progressive hearing loss. However, they showed better performance regarding the thresholds after implantation. The subjects with complications, although, suggested poorer performance in the auditory speech performance. The findings of poorer outcomes might depend on complications and brain functions. In addition, considering the blood test parameters, an independent elevated LDH and ChE at diagnosis were found to be associated with hereditary enzyme's metabolic disease. Therefore, the value of LDH measurements in patients might be a helpful predictive parameter in hereditary diseases.

GJB2 gene mutations in newborns with non-syndromic hearing impairment in Northern China

Mutations in GJB2 account for the majority of recessive forms of prelingual hearing loss. However, in most previous studies it was not possible to distinguish between congenital (present at birth) and non-congenital prelingual hearing loss. In the present study, the frequency of GJB2 alleles in 20 newborns with bilateral severe-to-profound non-syndromic hearing impairment (NSHI) who were found at birth through newborn hearing screening and clinical examination is reported. PCR was used to amplify the coding region of GJB2 gene followed by sequencing analyses. Fifty volunteers with normal hearing were included as controls. Results showed that three cases were 235delC/235delC homozygotes; one was 235delC/605ins46 compound heterozygotes, 605ins46 mutation was a novel mutation reported in the Chinese population; another was 235delC/299–300delAT compound heterozygotes. 25% (5/20) of the deafness in newborns studied was caused by GJB2 gene mutations. The frequency of 235delC allele carrier in patients and in control group was 22.5% and 1%, respectively. One case was identified as being a 235delC heterozygote without other mutations detected. Besides, multiple polymorphisms such as V27I, V37I, E114G, T123N were also detected. In conclusion, GJB2 analysis is an important test that identifies a major cause of newborns with bilateral severe-to-profound NSHI screened by universal newborn hearing screening in Northern China. The most common pathologic mutation of GJB2 in studied cases was 235delC. Molecular analysis and genetic counseling will be extremely important for congenital deafness present at birth.

Mutations of Cx26 gene (GJB2) for prelingual deafness in Taiwan.

Mutations in the Cx26 (GJB2) gene have been shown to be responsible for a major part of autosomal recessive non-syndromic inherited prelingual deafness. We have sequenced the coding region of GJB2 gene from 169 Taiwanese patients with prelingual deafness and 100 unrelated normal individuals. In the deaf patients, three mutations were found: two novel mutations, 551G-->A, and 299-300delAT, and one previously described mutation, 235delC. Four previously reported polymorphisms, 79G-->A, 109G-->A, 341A-->G, and 608T-->C, were also found in both deaf patients and normal individuals and one new possible polymorphism, 558G-->A, which was only found in a patient. Interestingly, we did not find the 35delG allele, which is commonly found in the Caucasian population, either in the patients or in normal individuals we examined. Our data also showed 235delC to be the most common type of mutation found in Cx26 mutants (approximately 57%). Therefore, based on our findings, we have developed a simple molecular test for the 235delC mutation and it should be of considerable help to those families to understand the cause of their children having the prelingual deafness.