Distribution characteristics and correlation analysis of GJB2 variation in patients with auditory neuropathy / 临床耳鼻咽喉头颈外科杂志

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.

Genetic characteristic analysis of slight-to-moderate sensorineural hearing loss in children / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze genetic factors and phenotype characteristics in pediatric population with slight-to-moderate sensorineural hearing loss. Methods:Children with slight-to-moderate sensorineural hearing loss of and their parents, enrolled from the Chinese Deafness Genome Project, were studied. Hearing levels were assessed using pure tone audiometry, behavioral audiometry, auditory steady state response（ASSR）, auditory brainstem response（ABR） thresholds, and deformed partial otoacoustic emission（DPOAE）. Classification of hearing loss is according to the 2022 American College of Medical Genetics and Genomics（ACMG） Clinical Practice Guidelines for Hearing Loss. Whole exome sequencing（WES） and deafness gene Panel testing were performed on peripheral venous blood from probands and validations were performed on their parents by Sanger sequencing. Results:All 134 patients had childhood onset, exhibiting bilateral symmetrical slight-to-moderate sensorineural hearing loss, as indicated by audiological examinations. Of the 134 patients, 29（21.6%） had a family history of hearing loss, and the rest were sporadic patients. Genetic causative genes were identified in 66（49.3%） patients. A total of 11 causative genes were detected, of which GJB2 was causative in 34 cases（51.5%）, STRC in 10 cases（15.1%）, MPZL2 gene in six cases（9.1%）, and USH2A in five cases（7.6%）.The most common gene detected in slight-to-moderate hearing loss was GJB2, with c. 109G>A homozygous mutation found in 16 cases（47.1%） and c. 109G>A compound heterozygous mutation in 9 cases（26.5%）. Conclusion:This study provides a crucial genetic theory reference for early screening and detection of mild to moderate hearing loss in children, highlighting the predominance of recessive inheritance and the significance of gene like GJB2, STRC, MPZL2, USH2A.

Results of combined newborn hearing and deafness gene screening in Yuncheng area of Shanxi Province / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical significance of combined newborn hearing and deafness gene screening in Yuncheng area of Shanxi Province.@*METHODS@#Results of audiological examinations, including transient evoked otoacoustic emission and automatic discriminative auditory brainstem evoked potentials, for 6 723 newborns born in Yuncheng area from January 1, 2021 to December 31, 2021, were retrospectively analyzed. Those who failed one of the tests were considered to have failed the examination. A deafness-related gene testing kit was used to detect 15 hot spot variants of common deafness-associated genes in China including GJB2, SLC26A4, GJB3, and mtDNA12S rRNA. Neonates who had passed the audiological examinations and those who had not were compared using a chi-square test.@*RESULTS@#Among the 6 723 neonates, 363 (5.40%) were found to carry variants. These have included 166 cases (2.47%) with GJB2 gene variants, 136 cases (2.03%) with SLC26A4 gene variants, 26 cases (0.39%) with mitochondrial 12S rRNA gene variants, and 33 cases (0.49%) with GJB3 gene variants. Among the 6 723 neonates, 267 had failed initial hearing screening, among which 244 had accepted a re-examination, for which 14 cases (5.73%) had failed again. This has yielded an approximate prevalence of hearing disorder of 0.21% (14/6 723). Among 230 newborns who had passed the re-examination, 10 (4.34%) were found to have carried a variant. By contrast, 4 out of the 14 neonates (28.57%) who had failed the re-examination had carried a variant, and there was a significant difference between the two groups (P < 0.05).@*CONCLUSION@#Genetic screening can provide an effective supplement to newborn hearing screening, and the combined screening can provide a best model for the prevention of hearing loss, which can enable early detection of deafness risks, targeted prevention measures, and genetic counseling to provide accurate prognosis for the newborns.

A prospective study of genetic screening of 2 060 neonates by high-throughput sequencing / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of genetic screening by high-throughput sequencing (HTS) for the early diagnosis of neonatal diseases.@*METHODS@#A total of 2 060 neonates born at Ningbo Women and Children's Hospital from March to September 2021 were selected as the study subjects. All neonates had undergone conventional tandem mass spectrometry metabolite analysis and fluorescent immunoassay analysis. HTS was carried out to detect the definite pathogenic variant sites with high-frequency of 135 disease-related genes. Candidate variants were verified by Sanger sequencing or multiplex ligation-dependent probe amplification (MLPA).@*RESULTS@#Among the 2 060 newborns, 31 were diagnosed with genetic diseases, 557 were found to be carriers, and 1 472 were negative. Among the 31 neonates, 5 had G6PD, 19 had hereditary non-syndromic deafness due to variants of GJB2, GJB3 and MT-RNR1 genes, 2 had PAH gene variants, 1 had GAA gene variants, 1 had SMN1 gene variants, 2 had MTTL1 gene variants, and 1 had GH1 gene variants. Clinically, 1 child had Spinal muscular atrophy (SMA), 1 had Glycogen storage disease II, 2 had congenital deafness, and 5 had G6PD deficiency. One mother was diagnosed with SMA. No patient was detected by conventional tandem mass spectrometry. Conventional fluorescence immunoassay had revealed 5 cases of G6PD deficiency (all positive by genetic screening) and 2 cases of hypothyroidism (identified as carriers). The most common variants identified in this region have involved DUOX2 (3.93%), ATP7B (2.48%), SLC26A4 (2.38%), GJB2 (2.33%), PAH (2.09%) and SLC22A5 genes (2.09%).@*CONCLUSION@#Neonatal genetic screening has a wide range of detection and high detection rate, which can significantly improve the efficacy of newborn screening when combined with conventional screening and facilitate secondary prevention for the affected children, diagnosis of family members and genetic counseling for the carriers.

Analysis of result of gene screening of neonatal deafness in Huizhou and surrounding urban areas / 中华医学遗传学杂志

OBJECTIVE@#To detect common pathogenic variants associated with congenital deafness among neonates from Huizhou and surrounding areas and discuss its implications.@*METHODS@#Thirteen hot-spot mutations in four most common pathogenic genes were screened among 20 934 neonates from March 2017 to December 2019.@*RESULTS@#In total 760 neonates were found to carry common pathogenic variants (3.63%). Sixty two neonates have carried homozygous/compound heterozygous variants or homoplasmy/heteroplasmy mutations of mtDNA (0.29%). Further analysis of five abnormal cases revealed that 3 of them have carried compound heterozygous mutations of GJB2 gene, and 2 were due to compound heterozygous variants of the CDH23 gene.@*CONCLUSION@#Genetic testing has a great clinical significance for the prevention and reduction of congenital hearing loss, but the scope needs to be updated and redefined by removing mutation sites with a very low rate, adding new significant sites, and improvement of the technical strategies.

Analysis of GJB2, SLC26A4, GJB3 and 12S rRNA gene mutations among patients with nonsyndromic hearing loss from eastern Shandong / 中华医学遗传学杂志

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.

Hipoacusia neurosensorial no sindrómica: caracterización molecular, desempeño auditivo y tratamiento en pacientes con mutaciones en las conexinas 26 y 30 / Non-syndromic sensorineural hearing loss: molecular characterization, auditory performance, and treatment in patients with connexin 26 and 30 mutations

La hipoacusia congénita o de aparición temprana es un trastorno sensorial muy frecuente en niños. Las causas son diversas, pueden intervenir factores genéticos y/o ambientales. El 80% de la sordera hereditaria es no sindrómica y de herencia autosómica recesiva. Hasta un 50% de estos casos se deben a mutaciones en el locus DFNB1 donde están localizados los genes GJB2 y GJB6, que codifican las conexinas 26 y 30, dos proteínas que se expresan predominantemente en la cóclea. Se han reportado más de 100 mutaciones en el gen GJB2, con una mutación muy frecuente, 35delG, que representa hasta un 85% de los alelos mutados. Una deleción en el gen GJB6, (delGJB6-D13S1830), surge como la segunda mutación más frecuente. La hipoacusia debida a mutaciones en estos genes es de inicio prelocutivo, con un grado de severidad que varía de moderado a profundo, existiendo casos leves en menor proporción, con variaciones inter e intrafamiliares. Es generalmente estable, bilateral, y afecta a todas las frecuencias. El conocimiento de las causas genéticas de la hipoacusia ha permitido contar con nuevas herramientas para el diagnóstico, y como consecuencia, se ha optimizado el asesoramiento genético y facilitado el diagnóstico precoz de los pacientes, incluso en el período prenatal. La detección precoz tiene un impacto inmediato en la implementación de terapias que permiten una estimulación auditiva temprana. En esta revisión se describe el papel de las conexinas en la fisiología auditiva, así como también las características moleculares y audiológicas y el desempeño auditivo con audífonos e implante coclear en pacientes que presentan mutaciones en las conexinas 26 y 30.

Congenital or early appearing hearing loss is a very common sensory disorder in children. The causes for the disorder are diverse and genetic as well as environmental factors may be involved. Overall, 80% of the hereditary deafness is non-syndromic and of autosomal recessive inheritance. Up to 50% of the cases are associated with mutations in the DFNB1 locus that contains the GJB2 and the GJB6 genes encoding connexins 26 and 30, two proteins that are predominantly expressed in the cochlea. More than 100 mutations of the GJB2 have been reported. The 35delG is a common mutation accounting for up to 85% of the mutated alleles. A deletion in the GJB6 gene, (delGJB6-D13S1830), is the second most frequent mutation found. Hearing loss due to mutations in these genes has an onset before speech develops and degree of severity varies from moderate to severe, with a lower incidence of mild cases and inter- and intrafamily variations. The condition is usually stable, bilateral, and affecting all frequencies. Increased knowledge on the genetic causes of hearing loss has allowed for the development of new diagnostic tools and consequently, improvement of genetic counseling and early, even prenatal, diagnosis. Early detection has an immediate impact with implementation of early auditory stimulation therapies. In this review the role of connexins in auditory physiology described, as well as molecular and audiological features and auditory performance with hearing aids and cochlear implants in patients with connexins 26 and 30 mutations.

Evaluation of electrocardiographic parameters in patients with hearing loss genotyped for the connexin 26 gene (GJB2) mutations / Avaliação dos parâmetros eletrocardiográficos em pacientes com perda auditiva genotipada para mutações do gene conexina 26 (GJB2)

Abstract Introduction: Several studies have associated congenital sensorineural hearing loss in children with prolongation of the cardiac parameter QTc. The cause of this association is unknown. At the same time, mutations in GJB2, which encodes connexin 26, are the most common cause of congenital hearing impairment. Objective: To compare electrocardiographic parameters (PR interval, QRS complex, and QTc interval) in patients with hearing loss who were tested for mutations in GJB2 and GJB6 to investigate whether these mutations affect electrical activity of the heart. Methods: 346 patients (176 males, 170 females) with sensorineural hearing loss of 30 dB HL or more, aged 21.8 ± 19.9 years (including 147 children <14 years), underwent both genetic study for GJB2 and GJB6 mutations and electrocardiography. Results: Mutations in GJB2, including homozygotes and heterozygotes, were found in 112 (32%) patients. There were no significant differences in ECG parameters between groups of patients with and without mutations in GJB2. No differences were observed either in men (mean PR with mutation: 155 ± 16.6 vs. 153.6 ± 30.1 without; QRS: 99.9 ± 9.9 vs. 101.1 ± 15.4; QTc: 414.9 ± 29.9 vs. 412.4 ± 25.7) or women (mean PR with: 148.7 ± 21 vs. 143.8 ± 22.8 without; QRS: 94.8 ± 7.6 vs. 92.9 ± 9.6; QTc: 416.8 ± 20.6 vs. 424.9 ± 22.8). In similar fashion, we did we find any significant differences between groups of children with and without GJB2 mutations (mean PR with: 126.3 ± 19.6 vs. 127 ± 19.7 without; QRS: 80.7 ± 9.5 vs. 79.4 ± 11.6; QTc: 419.7 ± 23.5 vs. 419.8 ± 24.8). Conclusion: No association was found between the presence of GJB2 mutations encoding connexin 26 in patients with hearing loss and their ECG parameters (PR, QRS, QTc).

Resumo Introdução: Vários estudos têm associado a perda auditiva neurossensorial congênita em crianças ao prolongamento do parâmetro cardíaco QTc. A causa dessa associação é desconhecida. Ao mesmo tempo, as mutações no GJB2, que codifica a conexina 26, são a causa mais comum de deficiência auditiva congênita. Objetivo: Comparar parâmetros eletrocardiográficos (intervalo PR, complexos QRS e intervalo QTc) em pacientes com perda auditiva que foram testados para mutações no GJB2 e GJB6 para investigar se essas mutações afetam a atividade elétrica do coração. Método: Foram submetidos a estudo genético para mutações de GJB2 e GJB6 e eletrocardiograma 346 pacientes (176 homens, 170 mulheres) com perda auditiva neurossensorial de 30 dB ou mais, com média de 21,8 ± 19,9 anos (incluindo 147 crianças <14 anos). Resultados: Mutações no GJB2, inclusive homozigóticos e heterozigóticos, foram encontradas em 112 (32%) pacientes. Não houve diferenças significativas nos parâmetros de ECG entre grupos de pacientes com e sem mutações no GJB2. Não foram observadas diferenças em homens (PR médio com mutação: 155 ± 16,6 vs. 153,6 ± 30,1 sem mutação; QRS: 99,9 ± 9,9 vs. 101,1 ± 15,4; QTc: 414,9 ± 29,9 vs. 412,4 ± 25,7) nem em mulheres (PR médio com: 148,7 ± 21 vs. 143,8 ± 22,8, sem; QRS: 94,8 ± 7,6 vs. 92,9 ± 9,6; QTc: 416,8 ± 20,6 vs. 424,9 ± 22,8). Da mesma forma, encontramos diferenças significativas entre os grupos de crianças com e sem mutações de GJB2 (PR médio com: 126,3 ± 19,6 vs. 127 ± 19,7, sem; QRS: 80,7 ± 9,5 vs. 79,4 ± 11,6; QTc: 419,7 ± 23,5 vs. 419,8 ± 24,8). Conclusão: Não foi encontrada associação entre a presença de mutações de GJB2 que codificam conexina 26 em pacientes com perda auditiva e seus parâmetros de ECG (PR, QRS, QTc).

Screening of mutations of deafness-related genes in women of child-bearing age from Shijiazhuang area / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for mutations of deafness-related genes among ethic Chinese women of child-bearing age.</p><p><b>METHODS</b>In 324 women, 9 mutational sites in 4 deafness-related genes (SLC26A4, GJB3, GJB2 and mtDNA 12s rRNA) were screened using a gene chip.</p><p><b>RESULTS</b>Twenty 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.</p><p><b>CONCLUSION</b>Women 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.</p>

A novel technique for simultaneous multi-gene mutation screening in 225 patients with nonsyndromic hearing loss / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>Using simultaneous multi-gene mutation screening to investigate the new method molecular epidemiological basis of 225 patients with nonsyndromic hearing loss in Tianjin, and verifying the for simultaneous multi-gene mutation screening.</p><p><b>METHODS</b>Two hundred and twenty-five patients with severe non-syndromic deafness from Tianjin CDPF and Association of the Deaf were included in the study. The single nucleotide polymorphisms scan, (SNPscan) technique was used for screening the 115 spots mutations in three common deafness-related genes (GJB2, SLC26A4, mtDNA 12S rRNA) of patients with nonsyndromic hearing loss in Tianjin. We verified the results by Sanger sequencing.</p><p><b>RESULTS</b>Among the 225 patients, there were 111 cases of deafness caused by mutation (49.3%). Using this method, up to 50% of the patients in our study were identified to have hereditary HL caused by mutations in the three genes. 56 patients with the GJB2 mutations were detected (24.9%), including 30 cases of homozygous mutations (13.3%), 26 patients (11.6%) of compound heterozygous mutations, and 21 cases (9.33%) of single heterozygous mutations. 50 patients with the SLC26A4 mutations were detected (22.2%), including 22 cases of homozygous mutations(9.8%), 28 patients (12.4%) of compound heterozygous mutations, and 22 cases (9.8%) of single heterozygous mutations. mtDNA 12S rRNA A1555G mutation was detected in 5 patients (2.2%). mtDNA 12S rRNA 1494C>T mutation was not detected. We verified the results by Sanger sequencing. The accuracy of the sequencing results was 100%. The SNPscan cost eight hours and 160 yuan (each sample).</p><p><b>CONCLUSIONS</b>Applying SNPscan technology can be accurate, rapid and cost-effective diagnostic screening in patients with hearing loss for etiology investigation. It is expected to become an effective means of large-scale genetic testing for hereditary deafness.</p>

Children's hearing behavior observations and high risk individual genetic screening for late-onset hearing loss early detection and intervention exploring a basic-level hospitals model / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the methods to detect and intervene children's late-onset hearing loss early which are suitable for basic-level hospitals.@*METHOD@#Udiology and imaging diagnosis had been given to the children who passed the newborn hearing screening but showed auditory behavior disorders in the growth process, and individualized interventions were given according to the results of diagnosis. Seven children with high risk for hereditary deafness were sent to superior hospital and had molecular screening of common mutations of inherited deafness carried out, then corresponding prevention guidance and intervention were given to them.@*RESULT@#Fifty-two cases with late-onset hearing loss or verbal disorders were detected by auditory behavior observations,including 4 cases of auditory neuropathy, 4 cases of unilateral sensorineural deafness, 27 cases of secretory otitis media. 13 cases of bilateral sensorineural deafness and 4 cases of autism. Seven newborns with high risk of hereditary deafness were sent to the Third Affiliated Hospital of Sun Yat-Sen University and received molecular screening of common mutations of inherited deafness. One case with GJB2 compound heterozygous mutations was detected and followed up to 4 years old, he was found bilateral moderate hearing loss and accepted the hearing aids at 2 years old. Mitochondrial DNA 1555 a > G heterogeneity mutation in 2 cases and GJB2 235 delC single heterozygous mutations in 3 cases, no mutation in 1 case, all these 6 cases have been followed-up until now, their hearing are normal.@*CONCLUSION@#Children's auditory behavior observations and the superior hospitals referral performing high risk individual screening for newborns with high risk for hereditary deafness can detect children's late-onset hearing loss in time, this model is suitable for basic-level hospitals.

Analysis common gene mutation spots of 127 non-syndromic deafness natients in Guangxi Drovince / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the mutation characteristics of common deafness gene from 127 non-syndromic hearing loss patients in Guangxi province.@*METHOD@#Deafness-related gene mutations detection kit was used to detect 15 mutation sites in four deafness-associated genes, and a total of 127 hearing impaired patients were tested. The samples that could not be diagnosed with DNA microarray were subjected to PCR and sequenced to detect other mutations.@*RESULT@#Among the 127 patients with non-syndromic deafness, the total mutation rate is 8.66% (11/127), including GJB2 235delC homozygous in 3 cases (2.36%), 235delC single heterozygous mutation in 2 cases (1.57%), GJB2 235delC and 109 A > G mutations in 2 cases (1.57%); SLC26A4 1229C > T homozygous in 1 case (0.79%), IVS7-2A > G, IVS11 + 47T > C and 15448insC mutaion in 2 cases (1.57%); mitochondrial 12S rRNA gene mutations were not detected. The result indicates that GJB2 and SLC26A4 were the main genes in this study, and the mutation rate is significantly lower than the national average level. Three new mutations (SLC26A4 IVS11 + 47T > C,1548insC and GJB2 109A > G) were found. There may be rare mutations among sites or genes associated with deafness in Guangxi.

Analysis of deafness-related gene mutations in 100 non-syndromic hearing loss patients in Henan province / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To preliminarily determine the gene mutation frequency and the hotspots in Henan province, we analysed the deafness-related gene mutation in patients with non-syndromic hearing loss (NSHL).@*METHOD@#Genomic DNA samples of 100 patients with NSHL in Henan province were extracted from peripheral blood after clinical history inquiry and clinical examination, Four common deafness genes GJB2, SLC26A4, mitochondrial 12SrRNA, and GJB3 were detected by Sanger sequencing method,and then data analysis were conducted.@*RESULT@#Among 100 patients with NSHL. the gene mutation frequency was 44%. In these patients, 29 cases had GJB2 mutations, 13 cases had SLC26A4 gene mutations, and 3 cases had mitochondrial 12SrRNA mutations.@*CONCLUSION@#Among the patients with NSHL in Henan province, the most frequent mutation causing hereditary deafness was mutation in GJB2, followed by SLC26A4,and it will provide a theoretical basis to determine the etiology of deafness in Henan Province.

The sequencing analyze of 915 newborn with GJB2 heterozygous mutation in Beijing / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To determine GJB2 allelic mutant and estimate probability of hereditary hearing loss in newborn with GJB2 heterozygous mutation in Beijing.@*METHOD@#We performed genetic testing for sequencing of GJB2 gene for searching GJB2 allelic mutant in 915 newborn who received newborn deafness gene screening (GJB2 c. 235delC, GJB2 c. 299_300delAT, GJB2 c. 176191del16, GJB2 c. 35delG) in Beijing Tongren hospital, and the mutation were classified to pathogenic mutation,undefined variant and polymorphism.@*RESULT@#Four hundred (43.72%, 400/915) newborn were detected to carry at least one mutation allele in GJB2. 3 (0.33%, 3/915) newborn had pathogenic mutations (c. 94C>T, c. 380G>T, c. 344T>G); 62 (6.76%, 62/915) newborn carried 14 undefined variant, 36 newborn had c. 109G>A (58.06%, 36/62),13 newborn had c. 368C>A (20.97%,13/62), six (c. 268C>G, c. 282C>T, c. 294G>C, 456C>T, c. 501G>A, c. 587T>C) are novel; 335 (36.61%, 335/915) newborn were polymorphism.@*CONCLUSION@#The probability of hereditary hearing loss is 7.09% in newborn with GJB2 heterozygous mutation in Beijing. It is noteworthy that c. 109G>A, c. 368C>A occupy a high proportion.

The research of rehabilitation effect of cochlear implantation for deaf children with gene mutation / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To assess the evaluation on auditory rehabilitation effect for 42 deaf children with GJB2 gene mutation after cochlear implantation to provide a reference for the cochlear implant effect evaluation of such patients.@*METHOD@#To conduct the detection on common genetic deafness gene mutation hotspots of hearing impaired children with cochlear implantation. To conduct auditory rehabilitation effect evaluation on 42 cases of patients with GJB2 genetic deafness after 3 months, 6 months and 12 months of the operation respectively. The single factor repeated measure ANOVA was applied to analyze whether there were significant difference among the results of initial consonant of a Chinese syllable recognition at 3 different stages after the operation, the results of vowel of a Chinese syllable recognition at 3 different stages after the operation, and the results of two-syllable recognition at 3 different stages after the operation.@*RESULT@#235delC is the high-incidence mutational site in 42 cases of patients with GJB2 genetic deafness, the total detection rate is up to 90.48%. There were significant differences in the initial consonant of a Chinese syllable recognition rate, the vowel of a Chinese syllable recognition rate, the two-syllable recognition rate as well as the vowel of a Chinese syllable recognition rate after 3 months, 6 months and 12 months of the operation (P < 0.01).@*CONCLUSION@#Cochlear implantation is a safe and effective measure for auditory reconstruction, it can help patients with GJB2 hereditary severe sensorineural deafness to improve auditory speech recognition.

Analysis of the deafness gene screening results from newborns in Shijiazhuang / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To build information repository of the carrying rate of neonatal deafness gene in Shijiazhuang.@*METHOD@#Blood samples were collected from the heel in 3-days neonates. Mutations of the deafness related genes were detected by the method of fluorescent PCR. Neonates received the detection of 6 mutation sites from 3 genes, including GJB2 (235delC, 299-300delAT), SLC26A4 (IVS7-2A> G, 2168A> G), mitochondrial DNA12S rRNA(1494C>T,1555A>G).@*RESULT@#There were 384 neonates who carried mutations among 421 subjects and the carrying rate was 4.08%, 158 (1.68%) newborns carried heterozygous mutations and 1 (0.01%) case carried homogeneous mutation of GJB2 (235 delC), 55 (0.58%) neonates carried heterozygous mutations of GJB2 (299-300delAT); 133 (1.41%) neonates carried heterozygous mutations and 1 (0.01%) homogeneous of SLC26A4(IVS7-2A>G),19 (0.20%) newborns carried heterozygous mutations of SLC26A4 (2168A>G). The numbers of neonates who carried homogeneous and heterogeneous mutation of mitochondrial 12S rRNA gene were 14 and 3 with carring rates of 0.15% and 0.03%. Two newborns were found to carry more than one mutation. One carried 235delC, IVS7-2A>G and 1555A>G and another carried 235delC and IVS7-2A>G.@*CONCLUSION@#The main mutational patterns were 235delC from GJB2 gene and IVS7-2A>G from SLC26A4 gene in Shijiazhuang newborns. The carrying rate information repository of neonatal deafness gene has been built preliminarily.

The effects of newborn genetic screening for GJB2 and hearing follow-ups / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To determine the prevalence of GJB2 mutations in newborns and provide clinical experience for newborn genetic screening.@*METHOD@#Blood samples of 23 836 newborns in Beijing from March 2012 to December 2013 were screened for hot spot mutations of GJB2 associated with hearing loss. The genetic screening results were comprehensively analyzed with hearing results in genetic counseling.@*RESULT@#One or two pathogenic mutations of GJB2 were spotted in 622(2. 61%) individuals. Among them, numbers of newborns with 1 mutation of c. 35deiG,c. 176191 del16,c. 235delC and c. 299300 delAT were 3,26,467 and 120. One compound heterozygote, and 5 homozygotes were also identified. Five hundred and fifty(88. 6%)newborns were followed up by telephones and SMS (short message service) and 325 newborns visit our genetic clinic regularly which were regarded as the research object. In the hearing screening, the referral rate for hearing loss in the first-step screening was 13.8% (45/325), and became 9.2% (30/325) upon retesting. Nine newborns (2. 8%) were diagnosed as hearing loss of different degrees as early as 3 months old,including 6 homozygous/compound heterozygote and 3 heterozygotes.@*CONCLUSION@#Patients with GJB2 mutations have various phenotype. Newborns with homozygous/compound heterozygous GJB2 mutations may pass the hearing screening at first. Carriers of GJB2 may also have hearing problems. The combination of genetic and audiological screening can play an important role in deafness detections of infants before key period of speech development.

Detection of common deafness-related genes among non-syndromic deafness patients from Shanxi province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the common causative genes and mutation sites for hereditary non-syndromic deafness in Shanxi.</p><p><b>METHODS</b>Peripheral blood samples were collected from regional schools for children with deafness. The samples were analyzed by matrix-assisted laser desorption ionization of flight mass spectrometry, and the results were verified by DNA sequencing.</p><p><b>RESULTS</b>For all samples, the 20 mutational sites of the 4 common causative genes were tested. As revealed, c.235delC of GJB2 gene has the highest mutational rate (13.67%). c.IVS7-2A>G of SLC26A (PDS) gene has a mutation rate of 17.67%, and c.1555A>G of mitochondrial 12S rRNA has a mutation rate of 2.00%. No mutations have been found with GJB3 gene. Sequencing analysis has suggested that the above results have a consistency rate of 99%.</p><p><b>CONCLUSION</b>Analysis of mutations of the 4 common deafness-related genes can facilitate early diagnosis and treatment for the disease. Matrix-assisted laser desorption ionization time of flight mass spectrometry is a reliable method for such a task.</p>

Analysis of common mutations of deafness-related genes in 2725 newborns / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for common mutations of deafness-related genes in order to determine the carrier rate, types of mutation, and their relevance to hearing loss.</p><p><b>METHODS</b>For 4 deafness-related genes GJB2, GJB3, 12S rRNA and SLC26A4, 20 common mutations were screened among 2725 newborns from Shaoxing, Zhejiang by matrix-assisted laser desorption ionization-time of flight-mass spectrometry.</p><p><b>RESULTS</b>Among the 2725 newborns,149 (5.47%) were diagnosed with mutations, which included 84 (3.08%) with GJB2 mutations, 13 (0.48%) with GJB3 mutations, 49 (1.80%) with SLC26A4 mutations and 3 (0.11%) with 12S rRNA mutations. Fourteen mutational hotspots were identified. The most common mutations have included GJB2 c.235delC (65 cases), SLC26A4 IVS7-2A>G (34 cases), GJB2 c.299_300delAT (13 cases), GJB3 c.538C>T (7 cases), GJB2 c.176_191del16 (6 cases) and GJB3 c.547G>A (6 cases).</p><p><b>CONCLUSION</b>The detecting rate for deafness-related gene mutations has been relatively high. To broaden the screening spectrum may improve such rate. Besides GJB2, 12S rRNA, SLC26A4, GJB3 also features a high mutation rate in the region.</p>

Screening of common deaf genes in pregnant women and prevention of deafness at birth / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the carrier rate for common mutations causing deafness among pregnant women in order to prevent births of deaf children.</p><p><b>METHODS</b>For 893 pregnant women, 2 mL peripheral venous blood was taken and DNA was extracted. A deafness DNA microarray screening was applied to such samples, and DNA sequencing was applied to husbands of women with positive screening results.</p><p><b>RESULTS</b>A total of 40 carriers were detected, with the overall mutation rate being 4.48%. Among such carriers, GJB2 235delC was the most common heterozygous mutation (18 cases) and the mutation rate was 2.02%. GJB2 299A-T heterozygous mutation was detected in 7 cases with a mutation rate of 0.78%. IVS7-2A to G heterozygous mutation was detected in 9 cases with a mutation rate of 1.02%. There were 2 cases carrying GJB3 heterozygous mutation and 2 cases of mitochondrial 12S rRNA heterozygous mutation, with a mutation rate of 0.22%. IVS7-2A>G with GJB3 538C>T double heterozygous mutation was detected in 1 case, and IVS7-2A>G with GJB2 299A-T double heterozygous mutation was detected in another case, with the mutation rate of each being 0.11%. DNA sequencing has failed to find presence of mutations in the same gene in the husbands. The results of neonatal hearing follow-up were all normal.</p><p><b>CONCLUSION</b>Applications of the deaf genes screening in pregnant women may play prove to be valuable for the early detection for neonatal deafness.</p>