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

Objective:To elucidate the correlation between the GJB2 gene and auditory neuropathy, aiming to provide valuable insights for genetic counseling of affected individuals and their families. Methods:The general information, audiological data（including pure tone audiometry, distorted otoacoustic emission, auditory brainstem response, electrocochlography）, imaging data and genetic test data of 117 auditory neuropathy patients, and the patients with GJB2 gene mutation were screened out for the correlation analysis of auditory neuropathy. Results:Total of 16 patients were found to have GJB2 gene mutations, all of which were pathogenic or likely pathogenic.was Among them, one patient had compound heterozygous variants GJB2[c. 427C>T][c. 358_360del], exhibiting total deafness. One was GJB2[c. 299_300delAT][c. 35_36insG]compound heterozygous variants, the audiological findings were severe hearing loss.The remaining 14 patients with GJB2 gene variants exhibited typical auditory neuropathy. Conclusion:In this study, the relationship between GJB2 gene and auditory neuropathy was preliminarily analyzed,and explained the possible pathogenic mechanism of GJB2 gene variants that may be related to auditory neuropathy.
Humans ; Connexins/genetics* ; Connexin 26/genetics* ; Hearing Loss, Central/genetics* ; Deafness/genetics* ; Mutation

OBJECTIVETo analyze the clinical features and pathological mutations in 44 families affected with hearing loss from southern Zhejiang, and to provide genetic counseling and prenatal diagnosis for 6 of the families.

METHODSMicroarray was employed to detect c.35delG, c.176del16, c.235delC and c.299-300delAT mutations of the GJB2 gene among 228 patients. For those carrying a single heterozygous mutation, the whole coding region of the GJB2 gene was analyzed by Sanger sequencing. For prenatal diagnosis, maternal DNA contamination was excluded by application of STR analysis.

RESULTSThe microarray assay has detected 49 patients with GJB2 mutations, which included 24 homozygous c.235delC mutations, 5 compound heterozygous c.235delC/c.176del16 mutations, 2 compound heterozygous c.235delC/c.299-300delAT mutations. Respectively, 16, 1 and 1 patients have carried single heterozygous c.235delC, c.176del16, and c.299-300delAT mutation. For the 16 patients, 7, 1, 1, 2, and 3 were detected by Sanger sequencing with a second heterozygous mutation of c.109G>A (2 of which were in conjunction with heterozygous c.176del16 and c.299-300delAT mutations), c.230G>A, c.427C>T, c.508-511 dupAACG, 79G>A+341A>G, respectively. Prenatal diagnosis revealed a compound heterozygous mutation in a fetus, heterozygous mutations in 4 fetuses, and no mutation of the GJB2 gene in 1 fetus.

CONCLUSIONThe proportion of carriers for GJB2 gene mutations in patients with hearing loss from southern Zhejiang has reached 21.5%. The c.235delC, c.176del16, and compound c.299-300delAT and c.109G>A mutations can cause moderate to severe hearing loss. In most affected families, Heterozygous mutations may be identified by sequencing the whole coding region of the GJB2 gene. Genetic analysis and prenatal diagnosis can prevent birth of further affected children.

Connexins ; genetics ; Female ; Genetic Testing ; methods ; Hearing Loss ; genetics ; Heterozygote ; Humans ; Male ; Mutation ; genetics ; Phenotype

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

OBJECTIVESTo review the identified deafness genes related to nonsyndromic hearing loss (NSHL) and summarize their expressions and functions in the cochlea and to introduce the current studies of molecular genetics on NSHL in China.

METHODSThe presented data are based on a review of the literature as well as the author' s experience with NSHL and communications with other researchers in China over the past 3 years.

RESULTSCurrently, 23 deafness genes related to NSHL have been cloned and identified. Some genes are associated with both NSHL and syndromic hearing loss (SHL), in both dominant and recessive deafness. Deafness genes have a highly specific expression pattern in the inner ear. Some functional categories are starting to emerge from a characterization of deafness genes. There are interacting genes in the genetic background that influence the extent of hearing impairment. The GJB3 gene, which is associated with high-frequency hearing impairment, was cloned in a Chinese laboratory. Mutations in some genes, such as GJB2 and mitochondrial 12S rRNA, have been screened in Chinese patients with NSHL. Mapping new deafness gene loci as well as identifying new genes and their functions is an active area of study in China.

CONCLUSIONSIt is challenging for us to continue identifying new deafness genes and analyze gene functions. By identifying genes responsible for monogenic hearing impairment, more insight may be gained into the molecular process of hearing and the pathology of hearing loss.

Chromosome Mapping ; Cloning, Molecular ; Connexin 26 ; Connexin 30 ; Connexins ; genetics ; Deafness ; genetics ; Humans ; Mutation

OBJECTIVETo investigate the clinical features and molecular mechanism of hidrotic ectodermal dysplasia (HED).

METHODSA clinical and gene study was performed for five generations (91 people) in the family of one proband with HED. GJB6 gene detection was performed for 7 patients and 3 normal people in this family.

RESULTSAmong the 91 people in this family, there were 17 HED patients, who were manifested as having dysplasia of the fingernails and toenails and sparse or absent hair or body hair. The male patients had a greater degree of sparse hair compared with female patients. In the younger generations, damage to the fingernails and toenails was gradually alleviated. There were patients in each generation, the patient's mother or father definitely had this disease. Both males and females developed this disease, and the inheritance pattern was autosomal dominant inheritance. A heterozygous missense mutation, 31G→A, in GJB6 gene was detected in all patients in this family, but this mutation was not detected in family members without the clinical manifestations of HED.

CONCLUSIONSHED is a hereditary disease with autosomal dominant inheritance and has the clinical features of dysplasia of the fingernails and toenails, hyperkeratosis of palms and soles, and sparse or absent hair or body hair. Male patients have a greater degree of sparse hair. In the younger generations, damage to the fingernails and toenails is gradually alleviated. The missense mutation 31G→A in the GJB6 gene may be one of the molecular mechanisms for HED.

Adolescent ; Connexin 30 ; Connexins ; genetics ; Ectodermal Dysplasia ; genetics ; Female ; Humans ; Male ; Mutation

Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.
Humans ; Connexin 30/genetics* ; Connexins/genetics* ; East Asian People ; Ectodermal Dysplasia/pathology* ; Phenotype