［Abstract］　Objective　To analyze the clinical phenotype of a family with hereditary non-syndromic deafness and to identify the deafness-causing gene mutation, and to analyze the characteristics of deafness caused by one of the identified pathogenic synonymous mutation in Chinese population in a large scale deaf population cohort. Methods　The clinical examinations such as questionnaire survey, audiological test and physical examination of the family members were completed, and their blood samples were collected for targeted genomic enrichment with massively parallel sequencing(MPS) and bioinformatics analysis to identify the causative gene. The identified pathogenic mutation detected in Chinese Deafness Genetics Consortium(CDGC) were summarized and analyzed. Results　The compound heterozygous mutations of MYO15A gene NM_016239.4: c.8182C>G(p.Arg2728Gly)/c.9861C>T(p.Gly3287=) were identified as the cause of deafness in this family with early-onset severe sensorineural deafness, among them, MYO15A gene c.9861C>T(p.Gly3287=) synonymous mutation led to gene dysfunction by altering splicing. The minor allele frequency was 0.2%(3/1 438) in the Zhuang population in Guangxi, China, but was not detected in other populations or public databases. Conclusion　The pathogenicity of MYO15A gene c.9861C>T(p.Gly3287=) in non-syndromic deafness patients in China has been confirmed in this study. This mutation is obviously enriched in Guangxi Zhuang Autonomous Region, China. It is emphasized that high-frequency and synonymous mutations are not absolute indicators of filtration in the identification of disease-causing genes, and extra care should be taken especially for the mutation with especially obvious enrichment in some regions.]]> 2023/5/31 10:09:26 WANG Si-ji, GUO Yi-lian, ZHONG Ming-jun, et al. 6true ［Abstract］　Objective　To analyze the clinical and genetic characteristics of a rare pedigree(No. HuB-341) having stapes ankylosis with broad thumbs and toes(SABTT) and to identify the disease-causing genes using the next-generation sequencing technology. Methods　The medical history investigation, physical examination, imaging examination and audiological examination of the family members were performed. The pedigree of the family was drawn. At the same time, the peripheral venous blood of the family members was collected and their deoxyribonucleic acids(DNAs) were extracted. Whole exome sequencing was conducted on the proband, and family verification was conducted on candidate genes by Sanger sequencing technology to identify the disease-causing genes in this pedigree. Results　The HuB-341 pedigree came from Wuhan, Hubei Province, and consisted of 3 persons in 2 generations. The proband was the only deaf patient in her family. She showed bilateral conductive hearing loss accompanied by characteristic facial features, broad toes, amblyopia and hyperopia. Whole exome sequencing was performed on the proband and a novel mutation in the NOG gene was identified, that is, c.679G>T, which caused the mutation of glutamic acid coding 227^th position to be a stop codon(p.Glu227Ter). The results of the family verification indicated that the mutation was a novel mutation, which was conservative among multiple species. Conclusion　The pedigree is clinically diagnosed as SABTT. A novel mutation of the NOG gene, c.679G>T(p.Glu227Ter), is identified through the whole exome sequencing and family validation of the proband. The mutation is a pathogenic mutation of the pedigree. The combination of clinical diagnosis and molecular diagnosis improves the understanding of this rare disease and provides scientific basis for genetic counseling of the pedigree.]]> 2023/5/31 10:09:26 ZAHNG Zhao, LU Yu, YANG Chang-liang, et al. 5true ［Abstract］　Objective　To identify the genetic etiology of a patient with severe sensorineural hearing loss, to clarify the pathogenicity of the detected mutation and the rehabilitation outcomes of the patient′s cochlear implant, and to provide genetic guidance for the family′s reproduction. Methods　Three samples were collected from a small deaf pedigree in Guangxi Zhuang Autonomous Region, including one patient with severe sensorineural hearing loss and his parents with normal hearing. The family members from the deaf pedigree were investigated for medical history, and were given physical and audiological examinations, and their peripheral venous blood was collected. Whole genome sequencing and bioinformatics analysis were conducted to identify the pathogenic genes and evaluate the outcomes of hearing and speech rehabilitation after cochlear implantation. Results　A homozygous new mutation of ESPN gene was the cause of deafness in the deaf pedigree, and the hearing and speech rehabilitation outcomes after cochlear implantation were good. Conclusion　The study identifies a new mutation of ESPN gene, which is the pathogenic cause of deafness in the deaf pedigree. The follow-up study finds that the speech rehabilitation after cochlear implantation is effective in the patient. This study enriches the mutant spectrum of hereditary deafness and has guiding significance for the preoperative evaluation of cochlear implantation.]]> 2023/5/31 10:09:26 LIU Yan, ZHONG Ming-jun, XIONG Wen-yu, et al. 4true ［Abstract］　Objective　To screen congenital deafness patients and their immediate family members in Guangxi region using the deafness gene chip detection method, and to analyze the main deafness-causing genes and the characteristics of deafness gene mutations in Guangxi region. Methods　A total of 336 patients with nonsyndromic hearing loss(NSHL) who were admitted to the People′s Hospital of Guangxi Zhuang Autonomous Region from December 2017 to December 2022 and their immediate family members were recruited as the research subjects. The peripheral blood of the patients was collected and their deoxyribonucleic acids(DNAs) were extracted, and the deafness gene chips were used to detect 16 mutation sites of 4 hot genes related to deafness. The 16 mutation sites included GJB2(35delG, 176-191del16, 235delC, 299-300delAT), GJB3(538C>T, 547G>A), SLC26A4(IVS7-2A>G, 2168A>G, 1174A>T, 1226G>A, 1229C>T, IVS15+5G>A, 1975G>C, 2027T>A) and mitochondrial 12S rRNA(1494C>T, 1555A>G), and the characteristics of these deafness gene mutations were analyzed statistically. Results　The common deafness gene mutations in 24 cases of 158 deaf patients(15.19%) were detected. Among the common deafness gene mutations, there were 15 cases(9.49%) of SLC26A4 gene mutation, 8 cases(5.06%) of GJB2 gene mutation, and 1 case(0.63%) of mitochondrial 12S rRNA mutation. The common deafness gene mutations in 22 cases of 178 deaf patients′ relatives with normal hearing were detected, with a detection rate of 12.36%. Among the common deafness gene mutations, there were 12 cases(6.74%) of SLC26A4 gene mutation and 10 cases(5.62%) of GJB2 gene mutation. Conclusion　SLC26A4 and GJB2 are the common deafness gene mutations of hereditary deafness in a population in Guangxi region, and the mutation rate of SLC26A4c.IVS7-2A>G site is the highest, followed by GJB2c.235delC mutation, which should be paid attention to by clinicians.]]> 2023/5/31 0:00:00 LIN Zuan-ping, YUN Lu, GAN Han-xiao, et al. 3true ［Abstract］　Objective　To study the mutation carrying rate and characteristics of the mutation of mitochondrial gene 12S rRNA in Zhuang people with normal hearing in Guangxi region, so as to provide reference for clinical prevention and treatment of deafness. Methods　Two mutation sites of mitochondrial gene 12S rRNA were detected in 150 cases of Zhuang people with normal hearing by using Crystal Core 15-Item Genetic Deafness Test Kit(Microarray Chip Method), a deafness gene mutation test kit. Sanger sequencing was performed on the positive results of the confirmed diagnosis. Results　Among the 150 subjects, mitochondrial gene 12S rRNA 1555 A>G mutation was detected in one case and its carrying rate was 0.67%. The case was confirmed as having 1555 A>G mutation by Sanger sequencing, and no mutation was found at 1494C>T site. Conclusion　It is of great significance to carry out mitochondrial gene 12S rRNA mutation screening among Zhuang people in Guangxi region, which can provide reasonable medication guidance and genetic counseling for mutation carriers and their maternal relatives, and is an effective measure to prevent drug-related deafness.]]> 2023/5/31 10:09:27 ZHANG Shao-jie, TANG Feng-zhu, WANG Rong, et al. 2true ［Abstract］　Objective　To observe the changes of oxidative stress level in spiral ganglion neurons(SGN) after the action of sodium salicylate(SS) on SGN of rat cochlea. Methods　Six Sprague-Dawley(SD) rats were divided into control group and SS group, with 3 rats in each group. The cochlear organs were treated with 5 mM SS for 48 hours after they were incubated for 48 hours. The control group was left untreated, and the main locations of reactive oxygen species(ROS) production in the cochlear organs were localized by immunofluorescence staining technique. Fifteen SD rats were divided into five groups, namely, control group, SS group, SS+N-acetyl-L-cysteine(NAC) group, positive control hydrogen peroxide(H₂O₂) group, and H₂O₂+NAC group, with 3 rats in each group. The SGN were isolated by acute isolation and treated with 5 mM SS, 5 mM SS combined with 100 μM NAC, 300 μM H₂O₂, 300 μM H₂O₂ combined with 100 μM NAC for 48 hours after 48 hours of primary culture, respectively, and the control group was left untreated. The mean fluorescence intensity of ROS fluorescent probe DCFH-DA in SGN of rats in each group was detected and quantified by fluorescent staining method; the CCK8 method was used to detect the survival rate of SGN cells. Results　In the cochlear organ culture, after SS treatment, immunofluorescence staining showed that ROS fluorescence was enhanced and mainly expressed in SGN, while the fluorescence intensities in the other cells were not significantly changed. To further quantify the fluorescence intensity, in primary culture SGN, after adding 5 mM SS treatment, the fluorescence staining method showed that the mean fluorescence intensity of ROS increased compared with that of the control group(P<0.001), which was consistent with the result of the H₂O₂ group(P<0.000 1). After the addition of the ROS inhibitor NAC, the mean fluorescence intensity of ROS decreased compared with that of the SS group(P<0.01). The results of the CCK8 method showed that the cell survival rate decreased by 41.34% after the action of SS compared to the control group(P<0.01), and after the addition of NAC, the cell survival rate increased by 36.05% compared to the SS group(P<0.01), and the difference was not statistically significant compared to the control group(P>0.05); cell survival rate in the H₂O₂ group decreased by 52.31% compared with that in the control group(P<0.001), and after the addition of NAC, cell survival rate increased by 34.73% compared with that in the H₂O₂ group(P<0.01). Conclusion　SS enhances the oxidative stress of SGN and causes SGN damage. Oxidative stress inhibitor NAC can reduce the oxidative stress of SGN and has a protective effect against SS-induced SGN damage.]]> 2023/5/31 10:09:27 ZHU Xiao-ting, HUANG Jia-lin, LIN Xiao-yu, et al. 1true