OBJECTIVE: To identify genetic mutations among patients with hearing loss but without common GJB2, SLC26A4, 12 SrRNA mutations. METHODS: Thirty-three patients were subjected to next-generation sequencing (NGS). Suspected mutations were verified by Sanger sequencing. RESULTS: Four patients were found to harbor previously known pathogenic variations, and four were found to carry suspicious pathogenic variations, which yielded a detection rate of 24.2%. CONCLUSION NGS can improve the detection rate for mutations underlying congenital hearing loss and improve the efficiency and accuracy of the diagnosis.
Connexins ; Deafness ; Hearing Loss, Sensorineural ; High-Throughput Nucleotide Sequencing ; Humans ; Membrane Transport Proteins ; Mutation ; Sulfate Transporters

OBJECTIVE: To determine the frequencies of deafness gene mutations among patients with non-syndromic hearing loss (NSHL) from northern Jiangsu province. METHODS: A total of 117 patients with NSHL were enrolled. The coding region of GJB2 gene, IVS7-2A>G and 2168A>G mutations of SLC26A4 gene, and 1555A>G and 1494C>T mutations of mitochondrial DNA 12S rRNA were subjected to Sanger sequencing. Patients in whom no mutation was detected were further tested by targeted gene capture and high-throughput sequencing. RESULTS: Among the 117 patients, 86 (73.50%) were found to carry mutations. GJB2 gene mutations were found in 61 patients (52.14%), including 22 (18.80%) with homozygous mutations and 39 (33.33%) with heterozygous mutations. SLC26A4 gene mutations were found in 19 patients (16.24%), including 4 (3.42%) with homozygous mutations and 15 with heterozygous mutations (14.53%). Mitochondrial 12S rRNA gene mutation was found in 6 patients (5.13%). Targeted gene capture and high-throughput sequencing of 8 patients identified 4 further cases, including 1 with RDX gene 129_130del and 76_79del compound heterozygous mutations, 1 with OTOF gene 1274G>C homozygous mutation, 1 with SLC26A4 gene 919-2A>G and IVS16-6G>A compound heterozygous mutation, and 1 with SLC26A4 gene 919-2A>G and A1673T compound heterozygous mutation. CONCLUSION The frequency of mutation among patients with NSHL from north Jiangsu was 73.50%, and GJB2 gene was most commonly mutated.
China ; Connexins ; DNA Mutational Analysis ; DNA, Mitochondrial ; Hearing Loss ; genetics ; Humans ; Membrane Proteins ; Mutation ; Sulfate Transporters

OBJECTIVE: To explore the characteristics of mutations of four common pathogenic genes (GJB2, SLC26A4, GJB3 and 12S rRNA) among patients with nonsyndromic hearing loss (NSHL) from eastern Shandong. METHODS: Peripheral blood samples of 420 NSHL patients were collected, and a hereditary-deafness-gene microarray was used to detect GJB2 c.235delC, c.299-300delAT, c.35delG and c.176del16 mutations, GJB3 c.538C>T mutation, SLC26A4 c.2168A>G and c.IVS7-2A>G mutations, and 12S rRNA c.1555A>C and c.1494C>T mutations. For patients carrying single heterozygous mutations, the coding regions of the above genes were analyzed with Sanger sequencing. RESULTS: The results of the microarray assay and Sanger sequencing showed that 84 patients (20.00%) carried GJB2 mutations, with c.235delC (16.43%) and c.299-300delAT (7.86%) being most common. Seventy-five patients (17.86%) carried SLC26A4 mutations, for which c.IVS7-2A>G accounted for 15.71%. In addition, 5.95% of patients carried 12S rRNA mutations. Only one patient was found to carried GJB3 mutation (c.538C>T). CONCLUSION Common pathogenic mutations for NSHL in eastern Shandong included GJB2 c.235delC and SLC26A4 c.IVS7-2A>G. Of note, 5.95% of patients were due to 12S rRNA m.1555A>G mutation, which gave a frequency greater than other regions of China.
China ; Connexin 26 ; Connexins ; DNA Mutational Analysis ; DNA, Mitochondrial ; Deafness ; Genes, rRNA ; Hearing Loss ; Humans ; Mutation ; RNA, Ribosomal ; Sulfate Transporters

OBJECTIVE: To investigate the frequencies of SLC26A4 hot spot mutations by genetic testing method in non-syndromic hearing loss children. The feasibility of genetic screening method in finding enlarged vestibular aqueduct syndrome was confirmed by temporal bone CT scan. METHOD: Ninety-two children with moderate-profound hearing loss were enrolled and DNA were extracted from peripheral blood. SLC26A4 IVS7-2A > G and H723R mutations were analyzed by direct sequencing. The individual with homozygous, compound heterozygous or heterozygous SLC26A4 mutations was given further temporal CT scan. RESULT: The sequencing results revealed 11 (12.0%) cases carrying SLC26A4 mutations, including 5 cases of bi-allelic mutation and 6 cases of single allelic mutation. CONCLUSION The SLC26A4 mutations has a high carrying rate in non-syndromic hearing loss children. The screening for the SLC26A4 gene mutations is useful in the diagnosis of EVAS.
Adolescent ; Child ; Female ; Genetic Testing ; Hearing Loss ; genetics ; Humans ; Male ; Membrane Transport Proteins ; genetics ; Mutation ; Sulfate Transporters ; Syndrome ; Vestibular Aqueduct

Antiporters/genetics* ; Carcinoma, Papillary/pathology* ; Humans ; Neoplasm Metastasis/genetics* ; Sulfate Transporters/genetics* ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/pathology*

OBJECTIVE: To identify the regional mutation hot spots characteristics, and then to establish a regional genetic screening programs. METHOD: Molecular epidemiological literatures about Chinese deafness gene GJB2, SLC26A4, mitochondrial DNA mutations from 2006 to the first half of 2011 were retrieved in Wanfang and Pubmed literature database. The primary data of these studies including the number of samples, demographic characteristics, mutation frequencies and so on,were analyzed statically. RESULT: Of 46 papers, 42 were included in this study. The patients all had non-syndromic sensorineural hearing loss and lived in 20 regions of China. A total of 18094 were counted and the average mutation frequencies were approximately 42.0%. The mutation frequencies of 235 delC were 16.34%, 299-300 delAT were 4.75% in GJB2 gene and IVS7-2A > G were 12.60%, 2168A > G were 2.32% in SLC26A4 gene and the mutation frequencies of 1555A > G, 1494C > T in mtDNA were 5.21%, 1.11% respectively. The statistical discrepancy was significant among mutation frequencies in different regions by chi2-test (P < 0.05). CONCLUSION Molecular epidemiological statistics show that the 6 locus are the mutation hot spots in Chinese people with non-syndromic hearing loss and can be used for genetic screening according to the specific regional mutation characteristics.
China ; epidemiology ; Connexin 26 ; Connexins ; genetics ; DNA, Mitochondrial ; genetics ; Deafness ; epidemiology ; genetics ; Genetic Testing ; Humans ; Membrane Transport Proteins ; genetics ; Mutation ; Sulfate Transporters

OBJECTIVE: To study molecular epidemiological basis of non-syndromic hearing loss in Yangzhou area. METHOD: The selected objects were 90 severe non-syndrome deafness students in special education schools in Yangzhou city, Jiangsu province. The deafness gene chip diagnostic kit was used for screening the nine hot spots mutations in four common deafness-related genes in Medical Testing Center of Northern Jiangsu People's Hospital. These nine hot spots gene mutations included GJB2 (35 delG, 176 del16, 235 delC and 299 delAT) GJB3 (538C > T), SLC26A4 (IVS7-2A > G, 2168A > G) and mtDNA 12S rRNA (A > G,1494C > T) mutation detection by line. RESULT: In 90 patients, 64 patients were found to carry deafness mutations by using gene chip diagnostic kit (the rate of mutation was 71.7%) GJB2 gene mutation in 40 cases (44.4%)which included 235 delC homozygous in 20 (22.2%) cases, 235 delC single heterozygous mutation in 4 cases (4.4%)and 235 delC and 299 delAT compound heterozygous mutations in 2 case (2.2%) separately. 299 delAT single heterozygous mutation in 2 case (2.2%), 299 delAT simple mutation in 2 case (2.2%). 176 del16 heterozygous mutations in 2 case, 176 del16 homozygous mutation in 2 case (2.2%). 176 del16 heterozygous mutations, and 235 del C heterozygous mutation in 6 cases (6.7%). SLC26A4 gene mutations in 22 cases (24.4%),which included IVS7-2A > G homozygous in 2 (2.22%) cases, IVS7-2A > G and 2168A > G compound heterozygous mutations in 2 cases (2.2%), IVS7-2A > G single heterozygous mutation in 18 cases (20.2%), and mtDNA 12S rRNA A > G mutation in 2 cases (2.2%), GJB3 mutations were not detected. CONCLUSION The deafness gene diagnostic techniques is worth applying for screening and diagnosis.
China ; epidemiology ; Connexin 26 ; Connexins ; genetics ; DNA, Mitochondrial ; genetics ; Education, Special ; Hearing Loss ; epidemiology ; genetics ; Homozygote ; Humans ; Membrane Transport Proteins ; genetics ; Mutation ; RNA, Ribosomal ; genetics ; Students ; Sulfate Transporters

OBJECTIVE: To detect additional variants for newborn carriers of single heterozygous variants of the GJB2 or SLC26A4 gene by genechip analysis in Changsha area, and explore the variation spectrum of deafness-related genes in this region. METHODS: For 462 newborns carrying single heterozygous variants of the GJB2 or SLC26A4 gene, all exons of the genes were subjected to Sanger sequencing. The pathogenicity of the variants was analyzed by database and literature search. RESULTS: For 305 newborns carrying a heterozygous GJB2 variant, 143 (46.49%) were found to carry additional variants, including 29 (9.51%) with c.109G>A likely pathogenic variant, and 1 (6.48%) with c.551G>A pathogenic variant. Among 153 newborns carrying single heterozygous variant of the SLC26A4 gene, 2 (1.31%) were found with a c.281C>T variant, and 1 (0.65%) with a c.1547_1548ins pathogenic variant. Among 4 newborns simultaneously carrying GJB2 and SLC26A4 variants, two were found to carry c.109G>A and c.844T>C variants (clinical significance unknown), respectively. CONCLUSION For newborns carrying single heterozygous variants of the GJB2 or SLC26A4 gene by genechip analysis, the detection rate for other variants is quite high. Sanger sequencing can significantly improve the detection rate of high-risk newborns and enrich the variant spectrum of deafness genes.
Connexins/genetics* ; DNA Mutational Analysis ; Deafness/genetics* ; Genetic Carrier Screening ; Heterozygote ; Humans ; Infant, Newborn ; Mutation ; Oligonucleotide Array Sequence Analysis ; Sulfate Transporters/genetics*

OBJECTIVE: To survey the etiology of sensorineural hearing loss with unknown reason and the incidence of the mutation of SLC26A4 2168A > G in Henan province. METHOD: The evaluation of hearing loss, etiologic survey, the molecular genetic analysis and temporal bone CT examination for genes common to hereditary hearing disorders were performed in 95 hearing-impaired patients in Henan province. RESULT: In the deafness group, the incidence of large vestibular aqueduct syndrome (LVAS) which correlates with SLC26A4 2168A > G is 6.32%. The incidence of the gene diagnosis conformed to the clinical one is 83.3%. CONCLUSION There is a high incidence of SLC26A4 2168 A > G mutation in sensorineural hearing loss with unknown reason. Molecular genetic screening for these mutations and genetic counseling are effective methods to prevent the occurrence of hereditary hearing loss.
Base Sequence ; China ; epidemiology ; Genetic Testing ; Hearing Loss, Sensorineural ; epidemiology ; genetics ; Humans ; Membrane Transport Proteins ; genetics ; Mutation ; Sulfate Transporters ; Vestibular Aqueduct

OBJECTIVE: To summarize and analyze the clinical characteristics of Mondini dysplasia with cerebrospinal fluid leakage, as well as preliminarily investigate the genetic mechanism of the disease. METHOD: The clinical data of 2 patients diagnosed as Mondini dysplasia with cerebrospinal fluid leakage treated in our hospital were analyzed. Blood samples of these two patients were obtained to extract DNA. We screened DNA samples for gene SLC26A4 mutations by using polymerase chain reaction and direct sequencing. The sequencing results were analyzed in DNASTAR software. RESULT: Both patients came to our hospital because of recurrent meningitis, and the fistula were both located in vestibular window. Patients were cured one-time after surgical closure of the leakages with temporalis + temporalis fascia + temporalis through the mastoid approach. No pathogenic mutations of gene SLC26A4 with exome sequencing were found. CONCLUSION Mondini dysplasia with cerebrospinal fluid leakage should be considered in patients with recurrent meningitis and hearing disorder. Temporal bone HRCT is helpful to the diagnosis. Surgical closure is an effective therapeutic method and may prevent recurrent meningitis. The molecular mechanism of simple Mondini dysplasia needs further study.
Cerebrospinal Fluid Leak ; physiopathology ; Cochlea ; pathology ; Fistula ; pathology ; Humans ; Hyperplasia ; genetics ; physiopathology ; Membrane Transport Proteins ; genetics ; Meningitis ; physiopathology ; Mutation ; Sulfate Transporters