BACKGROUNDMutations in GJB2 gene are a major cause of autosomal recessive congenital hearing loss and the cause in some rare cases of the autosomal dominant form. The purpose of this study was to investigate the frequency and the features of GJB2 mutations in the Chinese patients with congenital sensorineural deafness.

METHODSUsing PCR amplifying the entire coding region of GJB2 gene and direct DNA sequencing to analyze mutations in this gene among unrelated 69 cases with autosomal recessive congenital nonsyndromic deafness and 27 cases of dominant congenital deafness and 35 sporadic cases. We also detected mutations in GJB2 in 100 control subjects with normal hearing.

RESULTS17.4% (12/69) of the probands in the autosomal recessive, 7.4% (2/27) of dominant families and 5.7% (2/35) of the sporadic congenital deafness patients had deafness-causing mutations in GJB2, respectively. Nine types of the mutations in GJB2 were detected in the recessive and sporadic group. They consisted of five types of polymorphism, and four types of deafness-causing mutation with homozygous 35delG in 1 sporadic (1/35), and 235delC frameshift mutation in 1 sporadic (homozygotes) and 10 recessive patients (2 heterozygotes and 8 homozygotes), and homozygous 442G-->A missense mutation and homozygous 465T-->A nonsense mutation in 1 different recessive proband, respectively. The 465T-->A that related to recessive deafness was a novel mutation found by this study. The homozygous (10/69, 14.5%) and the heterozygous (2/69, 2.9%) GJB2 mutation in the recessive patients (12/69, 17.4%) and the homozygotes in the sporadic patient (2/35, 5.7%) all had congenital severe to profound sensorineural hearing loss. 511G-->A missense mutation and 299-300delAT frameshift mutation were found in two autosomal dominant congenital deafness families (2/27, 7.4%). The total mutation frequency of GJB2 was 12.2% (16/131) in the Chinese patients with congenital sensorineural deafness and 235delC was the most common deafness-causing mutation. Six types of mutation-5 types of polymorphism and 1 type of heterozygous deletion (235delC) mutation were found in the 100 control subjects. The carry rate of the most frequent type of mutation 235delC was 0.5% in the controls (1/200 alleles). 109G-->A was the most frequent (15/100, 15%) and 79G-->A was the second common (8/100, 8%) polymorphism in this population.

CONCLUSIONSThe general mutation rate of GJB2 is 12.2% (16/131) and the 235delC is the most common type of deafness-causing mutation in Chinese patients with congenital hearing loss. 465T-->A nonsense mutation that is associated to autosomal recessive deafness is a novel mutation found by this screening. 511G-->A and 299-300delAT mutations contribute to autosomal dominant hearing loss. The study further supports the view that the common types of mutation in GJB2 according to different ethnic background and that the mutation prevalence in the East Asian deafness population is lower than that in the white population.

Connexin 26 ; Connexins ; genetics ; Hearing Loss, Sensorineural ; genetics ; Humans ; Mutation

OBJECTIVETo screen for mutations of deafness-related genes among ethic Chinese women of child-bearing age.

METHODSIn 324 women, 9 mutational sites in 4 deafness-related genes (SLC26A4, GJB3, GJB2 and mtDNA 12s rRNA) were screened using a gene chip.

RESULTSTwenty women (6.17%) have carried mutations. These included 11 (3.40%) carrying a GJB2 gene mutation, 7 (2.16%) carrying a SLC26A4 gene mutation, 1 (0.31%) simultaneously carrying GJB3 and GJB2 gene mutations, and 1 (0.31%) carrying a mtDNA 12s rRNA gene mutation.

CONCLUSIONWomen of child-bearing age have a high rate for carrying mutations of common deafness-related genes, among which 235delC in GJB2 was most common. Prenatal screening of couples with normal hearing is an effective way to prevent birth of affected children.

Adult ; Connexin 26 ; Connexins ; genetics ; Deafness ; genetics ; Female ; Humans ; Mutation

Deafness refers to different degrees of hearing loss (HL). The factors leading to HL are complex, among which heredity is a major one. Nonsyndromic hearing loss (NSHL) accounts for 80% of hereditary deafness. More than 140 genes have been regarded to be closely related to NSHL. The mutation of GJB2 (gap junction protein, beta 2) gene accounts for 80% of NSHL and more than 50% of children NSHL, playing the most important role in deafness genes. This paper reviewed the studies on the association between GJB2 gene mutation and HL to provide reference for genetic diagnosis and counseling.
Connexin 26 ; Connexins ; genetics ; Deafness ; genetics ; Humans ; Mutation

Connexins (Cx) are membrane proteins and monomers for forming gap junction (GJ) channels. Cx46 and Cx50 are also known to function as conductive hemichannels. As part of an ongoing effort to find GJ-specific blocker(s), endocrine disruptors were used to examine their effect on Cx46 hemichannels expressed in Xenopus oocytes. Voltage-dependent gating of Cx46 hemichannels was characterized by slowly activating outward currents and relatively fast inward tail currents. Bisphenol A (BPA, 10 nM) reduced outward currents of Cx46 hemichannels up to ~18% of control, and its effect was reversible (n=5). 4-tert-Octylphenol (OP, 1 microM) reversibly reduced outward hemichannel currents up to ~28% (n=4). However, overall shapes of Cx46 hemichannel current traces (outward and inward currents) were not changed by these drugs. These results suggest that BPA and OP are likely to occupy the pore of Cx46 hemichannels and thus obstruct the ionic fluxes. This finding provides that BPA and OP are potential candidates for GJ channel blockers.
Connexins ; Endocrine Disruptors ; Gap Junctions ; Membrane Proteins ; Oocytes ; Xenopus

OBJECTIVETo assess the value of pre-gestational deafness-related mutation screening for the prevention and intervention of congenital deafness.

METHODSIn this study, 2168 couples with normal hearing were screened for common mutations associated with congenital deafness using real-time fluorescence quantitative PCR. The mutations have included GJB2 c.235delC and c.299_300delAT, SLC26A4 c.2168A>G and c.IVS7-2A>G, and mtDNA 12SrRNA c.1494C>T and c.1555A>G. For couples who have both carried heterozygous mutations of the same gene, genetic counseling and prenatal diagnosis were provided.

RESULTSAmong of the 4 336 individuals, 178 (4.06%) were found to carry a mutation. Mutation rate for c.235delC and c.299_300delAT of GJB2 gene, c.IVS7-2 A>G and c.2168 A>G of SLC26A4 gene, c.1555 A>G and c.1494 C>T of DNA 12S rRNA gene were 0.91%, 0.20%, 0.68%, 0.11%, 0.1% and 0.01%, respectively. For six couples who have both carried mutations of the same gene, all fetuses showed a normal karyotype, while DNA sequencing indicated that two fetuses have carried homozygous c.235delC mutation of the GJB2 gene, one carried a heterozygous c.235delC mutation of the GJB2 gene, one carried heterozygous mutation of GJB2 gene (c.299_300delAT), and two have carried a heterozygous mutation of c.IVS7-2A>G of the SLC26A4 gene.

CONCLUSIONPre-gestational screening for deafness gene mutation can facilitate avoidance the birth of affected children and has a great clinical value for the prevention and intervention of birth defect.

Connexins ; genetics ; Deafness ; congenital ; genetics ; prevention & control ; Female ; Humans ; Mutation ; Pregnancy ; Prenatal Diagnosis

OBJECTIVETo identify mutation of GJB2 gene and provide genetic counseling for a family affected with keratitis-ichthyosis-deafness (KID) syndrome.

METHODSGenomic DNA was extracted from peripheral blood samples with a standard phenol-chloroform method. PCR and Sanger sequencing were used to analyze potential mutation in the proband. Suspected mutation was verified with a PCR-high-resolution melting (PCR-HRM) method. T-clone sequencing was applied to determine the parental origin of the mutation.

RESULTSA heterozygous mutation, c.148G>A (p.Asp50Asn), which is located in the exon 1 of the GJB2 gene, was found in the proband. The results was confirmed by HRM analysis. Cloning sequencing suggested that the mutation was derived from the father's germline.

CONCLUSIONThe hot-spot mutation c.148G>A (p.Asp50Asn) in the GJB2 gene probably underlies the KID syndrome in this Chinese family. A PCR-HRM method has been established to rapidly detect common mutations associated with this disease.

Child ; Connexins ; genetics ; DNA Mutational Analysis ; Humans ; Keratitis ; genetics ; Male ; Mutation ; Pedigree

China has a large population with different levels of medical care among the eastern, central and western areas. The national universal newborn hearing screening (UNHS) programme was initiated in 1999 and then progressively implemented nationwide. A "National UNHS Experts Group" was set up, formulating the national UNHS administration rules and technological specifications. 3 March had been named as national "ear-care day" since 2000 and such social activities help make deafness prevention work more widely accepted. UNHS in China presently has 3 phases due to disparities in economic development. 1) Implementation in stages: in economically under-developed areas. 2) Implementation completed: in the coastal cities. 3) Beyond basic UNHS: i) Development of a completed UNHS system including follow-up and quality control based on the neonatal disease screening system, ii) Exploration of a new public health care programme: simultaneous screening of newborn hearing and ocular disease, iii) Carrying out of a multi-centre study on high-risk factors and GJB2 gene mutations in newborn with non-syndromic hearing impairment. The incidence of newborn bilateral hearing loss was 2.22 per 1000, and 2.74 per 1000 for unilateral hearing loss. Though UNHS have been carried out widely in the eastern parts of China, there are difficulties for its implementation in the western regions. Economic development and technical expertise are the main restricting factors.
China ; Connexins ; Hearing Tests ; Humans ; Infant, Newborn ; National Health Programs ; Neonatal Screening ; Program Evaluation

OBJECTIVETo probe into expression of connexin 43 (Cx43) in the meridians of the normal healthy rats and the relation among connexin, gap junction and meridian.

METHODSPowerVision two step immunohistochemical technique and ASIAS-2000 automatical image-scan analyzing system were used to detect Cx43 level and distribution in the Kidney and Bladder Meridians of the rat.

RESULTSCx43 expressed mainly in skin epithelia, fibroblasts and mast cells of the subcutaneous layer. And expression of Cx43 in the Kidney and Bladder Meridians was significantly more than that in the control lines (P < 0.01).

CONCLUSIONConnexins and gap junctions have close relation with the meridians, and the gap junctional intercellular communication may play an important role in the function of meridians.

Animals ; Cell Communication ; Connexin 43 ; metabolism ; Connexins ; Gap Junctions ; metabolism ; Meridians ; Rats

OBJECTIVEThis review discusses the experimental and clinical studies those show the expression of connexin 36 in the central nervous system and the possible role of connexin 36 in epileptic seizure.

DATA SOURCESAll articles used in this review were mainly searched from PubMed published in English from 1996 to 2012.

STUDY SELECTIONOriginal articles and reviews were selected if they were related to the expression of connexin 36 in the central nervous system and its role in epilepsy.

RESULTSThe distribution of connexin 36 is developmentally regulated, cell-specific and region-specific. Connexin 36 is involved in some neuronal functions and epileptic synchronization. Changes in the connexin 36 gene and protein were accompanied by seizures. Selective gap junction blockers have exerted anticonvulsant actions in a variety of experiments examined in both humans and experimental animals.

CONCLUSIONSConnexin 36 plays an important role in both physiological and pathological conditions in the central nervous system. A better understanding of the role of connexin 36 in seizure activity may contribute to the development of new therapeutic approaches to treating epilepsy.

Animals ; Central Nervous System ; metabolism ; Connexins ; metabolism ; Gap Junctions ; metabolism ; Humans ; Seizures ; metabolism

Atrial Fibrillation ; etiology ; Connexin 43 ; analysis ; Connexins ; analysis ; Fluorescent Antibody Technique ; Gap Junctions ; physiology ; Humans