Objective To examine the risk factors for increased burden of cerebral small vessel diseases(CSVD)in middle-aged and elderly patients with sudden sensorineural hearing loss(SSNHL).Methods The data were retrospec-tively collected from middle-aged and elderly patients who were admitted to the hospital due to SSNHL between May 2019 and May 2023.The patients were analyzed for their clinical manifestations,hearing test results,and radiological features.All enrolled patients were assessed for total CSVD burden,and patients with varying degrees of burdens(0,1,2,and≥3 points)were compared for their differences in the clinical features and hearing features.Ordinal logistic regression was conducted to identify the independent risk factors for increased total CSVD burden in middle-aged and elderly patients with SSNHL.Results A total of 206 patients with SSNHL were enrolled,including 94 males and 112 females,with an average age of(58.70±7.98)years.The numbers of patients with a total CSVD burden of 0、1、2,and≥3 points were 108(52.4%),54(26.2%),29(14.0%),and 15(7.2%),respectively.Univariate analysis showed significant differences between different CSVD burden groups in age,hypertension status,history of drinking,low-density lipoprotein>3.1 mmol/L,and presence of dizziness at the onset of disease(P<0.05).Logistic regression analysis demonstrated that aging(OR=1.050;95%CI 1.023-1.077),hypertension(OR=1.584;95%CI 1.036-2.422),history of drinking(OR=2.304;95%CI 1.415-3.754),and presence of dizziness at the onset of disease(OR=1.691;95%CI 1.085-2.637)were independent risk factors for in-creased CSVD burden in SSNHL patients aged 45 years and above.Conclusion Aging,hypertension,history of drink-ing,and dizziness at the onset of disease are independent risk factors for increased CSVD burden in middle-aged and el-derly patients with SSNHL.Clinicians should conduct radiological evaluations on these patients to identify pa-tients with CSVD at an early stage.

目的 初步建立满足信息录入、信息查询及信息统计三大基本功能的儿童听力门诊信息随访系统,提高信息录入效率和汇总效率,为临床及科研提供高效和便利的平台.方法 基于Microsoft Office Access数据库软件,根据儿童听力门诊信息随访系统的功能需求,结合临床"儿童听力诊断中心病例记录表",设计并搭建儿童听力门诊信息随访系统的基本框架.随机抽取北京同仁医院耳科门诊就诊儿童100例,分为A、B两组,每组50例,A组使用纸质版"儿童听力诊断中心病例记录表"录入门诊信息,B组使用儿童听力门诊信息随访系统录入,采用双尾t检验比较两组的录入时间,分析两组录入方式的效率.结果 初步建立了儿童听力门诊信息随访系统,主要包括"信息录入""信息查询"及"信息统计"三个功能模块;信息录入包括基本个人信息、病史、新生儿听力筛查结果、听力学诊断检查结果和耳聋基因检查结果等;信息查询主要实现通过患者姓名检索相应信息;信息统计可实现对录入信息的汇总和筛选,以及导出Excel等表格进行统计分析.A组信息录入平均时间为10.01±0.08分,B组为7.11±0.08分,差异有统计学意义(P＜0.000 1).结论 儿童听力门诊信息随访系统初步实现了信息录入、信息查询和信息统计的基本功能,且提高了信息录入效率,为临床及科研提供了一个高效、实用及安全的信息随访平台.

Objective:To analyze the clinical characteristics of unilateral acoustic neuroma（AN） with normal hearing, so as to provide evidence for early identification AN. Methods:Clinical datas from 73 patients of unilateral AN with normal hearing of Otorhinolaryngology Head and Neck Surgery of Beijing Tiantan Hospital affiliated of Capital Medical University from August 2019 to April 2022 admitted to department were retrospectively analyzed. All patients underwent pure tone audiometry（PTA）, speech discrimination score（SDS）, auditory brainstem response（ABR）, distortion product otoacoustic emission（DPOAE） and head enhanced MRI. Results:The incidence of normal hearing among patients with AN was 10.7%. Male∶female=1∶2.2; the mean age of the patients was（37.3±9.4） years; the mean tumor size was（24.2±11.2） mm. Tinnitus was the most common reason for visit; the patients who had headache and dizziness had larger tumors. Surgery was the main treatment, and the patients who underwent surgery had larger tumors than those of follow-up. Heterogeneous tumors were the most common type of MRI, homogeneous tumors were smaller than heterogeneous and cystic tumors. The sensitivity of ABR in the diagnosis of AN with normal hearing was 95.9%, and that of ≥20 mm tumors was 100%; prolonged Ⅴ-waves were the most common, patients with Ⅴ-wave deletion had larger tumors than those with normal or prolonged Ⅴ-waves. Patients who had the longer the Ⅴ-wave and the longer difference between Ⅰ-Ⅴ wave had larger tumors. DPOAE was not elicited at full frequency in 11 patients. There was no statistically significant difference in age among patients with different symptoms, treatments, types of MRI, ABR and DPOAE. Conclusion:AN of normal hearing was most common in 30-39 years old women. Patients had different symptoms, phenotypes of MRI and ABR. Patients with normal hearing who had tinnitus, dizziness, headache, facial paraesthesia, and recovery after sudden haring loss can be further examination of ABR and DPOAE for early identification AN. The sensitivity of ABR in diagnosis of hearing normal AN was 95.9%, and the abnormal type of Ⅴ-wave is related to tumor size.

目的 分析听神经瘤患者临床听力学特征,为听神经瘤的诊断提供参考依据.方法 回顾性分析首都医科大学附属北京天坛医院耳鼻咽喉头颈外科接诊的394例单侧听神经瘤患者临床资料,所有患者均行纯音测听、言语识别率、听性脑干诱发电位和颅脑增强MRI.结果 患侧听力正常者54例,轻度听力损失58例,中度63例,中重度45例,重度45例,极重度31例,全聋者98例;高频听力损失最多见.24.7％患者言语识别率和纯音测听下降不成比例.听性脑干诱发电位波形正常者8例,波形缺失者228例和其他波形异常者158例;听性脑干诱发电位诊断听神经瘤的敏感度:内听道内肿瘤85.7％,内听道外98.5％.结论 听神经瘤的听力学表型多样,听力正常者不能排除听神经瘤;听力损失程度不能预判肿瘤大小;纯音测听与言语识别率不一致应警惕蜗后病变;听性脑干诱发电位诊断听神经瘤敏感度随肿瘤增大而增加.

Objective:The aim of this study is to explore the genotype and hearing phenotype of deaf infants with mutation of GJB2 gene. Method:Subjects were 121 infants with GJB2 gene mutations who were treated in the Children's Hearing Diagnosis Center of Beijing Tongren hospital. All subjects were accepted to undertake the universal newborns hearing screening（UNHS） and series of objective audiometry, including auditory brainstem response, distortion product otoacoustic emission, auditory steady-state response and other audiological tests. All subjects were screened for nine pathogenic variants in four genes or all exons of the GJB2 gene, and then were diagnosed as infants with GJB2 gene mutations. Initially, analyzing their genotypes and hearing phenotypes generally. Then, the subjects were divided into two groups according to the genotypes: T/T group（truncated/truncated mutations, 89 cases） and T/NT group（truncated/non-truncated mutations, 32 cases）. Chi-square test was used to analyze the results of UNHS, hearing degree, audiogram patterns and symmetry/asymmetry of binaural hearing phenotype. Eventually, analyzing the results of UNHS. Result:The most common truncated mutation was c.235delC（64.88%, 157/242） and the most common non-truncated mutation was c.109G>A（11.16%, 27/242）. The homozygous mutation of c.235delC/c.235delC was the dominant in T/T group（38.84%, 47/121）, and the compound heterozygous mutation of c.235delC/c.109G>A was the dominant in T/NT group（18.18%, 22/121）. 81.82%（99/121） of subjects failed in UNHS, including 74.38%（90/121） with bilateral reference, 7.44%（9/121） with a single pass. The refer rate of UNHS of group T/T and T/NT were 86.52%（77/89） and 68.75%, respectively. There was a statistically significant difference between the two groups（P<0.05）. 85.95%（104/121） of subjects were diagnosed as hearing loss and 14.05%（17/121） of subjects were diagnosed as normal hearing. The degree of hearing loss: profound, severe, moderate and mild were 31.40%（38/121）, 19.01%（23/121）, 24.79%（30/121） and 10.74%（13/121）, respectively. There was no subjects with normal hearing in T/T group and individuals with severe and profound hearing loss accounted for the highest proportion（65.17%, 58/89）, while in T/NT group, normal hearing accounted for 53.13%（17/32） and mild and moderate hearing loss accounted for the highest proportion（37.5%, 12/32）. There was statistically significant difference between the two groups（P<0.05）. Of 104 patients（208 ears） with hearing loss, the audiogram patterns: flat, descending, ascending, residual, Valley and other types were 49.03%（102/208）, 12.02%（25/208）, 8.65%（18/208）, 7.69%（16/204）, 3.36%（7/204） and 19.23%（40/204）, respectively. The two most common types in T/T group were flat（47.19%, 84/178） and other types（20.22%, 36/178）, while in T/NT group were flat（60.00%, 18/30） and ascending（20.00%, 6/30）. There was statistically significant difference between the two groups（P<0.05）. There were 50 cases（48.07%） with symmetrical hearing phenotype and 54 cases（51.93%） with asymmetrical hearing phenotype. Asymmetry was predominant in T/T group（53.93%, 48/89）, and symmetry was predominant in T/NT group（60.00%, 9/15）. There was no statistically significant difference between the two groups（P>0.05）. Conclusion:In this study, c.235delC/c.235delC homozygous mutation was dominant in T/T group and c.235delC/c.109G>A heterozygous mutation was dominant in T/NT Group. The hearing phenotypes in T/T group were mostly bilateral asymmetric severe hearing loss, and those in T/NT Group were bilateral symmetric mild to moderate hearing loss, special attention should be paid to the audiological characteristics of different genotypes.

OBJECTIVES:The present study aimed to determine the status of a universal newborn hearing screening (UNHS) program being conducted in parts of China, by comparing differences in the program findings between 2016 and 2017, as well as across regions in China.METHODS:This study investigated a nationally representative sample of newborns from 26 provinces, autonomous regions, and municipalities in mainland China. A ''Newborn Hearing Screening Survey'' questionnaire was sent to 43 hearing screening institutions throughout China and the data were analyzed, with appropriate quality control throughout the study process.RESULTS:Twenty-six questionnaires, covering 55.88% (19/34) of the provincial administrative regions in China were appropriately completed. The overall sampling frame comprised 238,795 (year 2016) and 229,185 (year 2017) newborns, respectively. We found differences between two years, the initial screening coverage in 2017 (96.10%) was higher than that in 2016 (94.96%); the referral rate at initial screening in 2017 (9.21%) was lower than that in 2016 (10.26%); and the rescreening rate in 2017 (73.50%) was higher than that in 2016 (68.44%). We found differences across three regions, the rescreening rate were highest in West China, the referral rate at rescreening and the referral rate to diagnostic audiological assessment diagnosis were both highest, while the hearing-loss rate was lowest, in the East China in two years. Overall, 61.54% (n = 16) reported using otoacoustic emissions (OAEs), while 38.46% (n = 10) reported using OAEs in combination with automated auditory brainstem response (AABR) tests, for the initial screening. For rescreening, most sites (n = 19, 73.08%) reported using OAEs in combination with AABR, followed by OAEs only (n = 4, 15.38%) and AABR only (n = 3, 11.54%). Of the twenty-six institutions, 57.69% (n = 15) were equipped with a digital information management system for UNHS program, East China had the highest rate of it (81.82%, 9/11).CONCLUSIONS:This study indicated that implementation of a UNHS program had essentially been achieved in many regions of China under the guidance of technical specifications for newborn hearing screening. Compared with 2016, the overall quality of the UNHS program had improved in 2017 and that in East China was better than in the Midland and West China. However, national quality control of the UNHS program is still required to enhance the quality of the program and public education needs to be emphasized to improve the rescreening and reception rate.

目的 评价耳声发射(OAE))、自动听性脑干反应(AABR)及OAE+AABR用于新生儿听力筛查时听力损失的检出效能.方法 通过Cochrane Library、Pubmed、Embase等数据库检索2000～2018年间国内外发表的应用OAE、AABR及OAE+AABR进行新生儿听力筛查的文献,设定文献筛选标准,使用STATA15.0软件对相关数据进行统计分析,对各筛查技术对听力损失检出的灵敏度及特异度进行Meta分析.结果 共纳入符合要求的文献13篇,三种筛查方法的灵敏度合并效应值OAE为93％(87％～96％),AABR为70％(62％～77％),OAE+AABR为97％(87％～99％);特异度合并效应值OAE为94％(84％～98％),AABR为98％(95％～100％),OAE+AABR为97％(92％～99％);SROC曲线下面积OAE为96％,AABR为76％,OAE+AABR为99％;OAE+AABR联合筛查的灵敏度合并效应值最高,SROC曲线下面积最大;AABR筛查的特异度合并效应值最高.结论 OAE+AABR联合筛查对听力损失的检出效能可能优于仅使用OAE或AABR,建议新生儿听力复筛中采用OAE+AABR联合筛查.

The current study investigated how the FOXI1 and KCNJ10 genes were affected in infants with a single-allele mutation in the SLC26A4 gene, and it determined the audiological phenotypes of infants with double heterozygous mutations (DHMs) in the three genes. Subjects were 562 infants with a single-allele SLC26A4 mutation detected during neonatal deafness genetic screening; the infants were seen as outpatients by Otology at Beijing Tongren Hospital. All subjects underwent SLC26A4 sequencing. Twenty infants had a second-allele variant while the remaining 542 had an SLC26A4 single-allele mutation. Infants also underwent FOXI1 and KCNJ10 sequencing. All patients with double heterozygous mutations in the aforementioned genes underwent an audiological evaluation and a limited imaging study; variants and audiological phenotypes were analyzed. Of 562 patients, 20 had SLC26A4 bi-allelic mutations; 8 carried single mutations in both SLC26A4 and KCNJ10. No pathogenic mutations in the FOXI1 gene were found. Four missense mutations in KCNJ10 were detected, including c.812G>A, c.800A>G, c.53G>A, and c.1042C>T. Eight individuals with a DHMs all passed universal newborn hearing screening, and all were found to have normal hearing. These data suggest that individuals with an SLC26A4 single-allele mutation, combined with FOXI1 or KCNJ10 gene mutations, do not suffer hearing loss during infancy, though this finding is worthy of further follow-up and in-depth discussion.

目的 分析0～6岁永久性听力损失儿童的确诊年龄及发现途径.方法 回顾性分析经北京同仁医院儿童听力诊断中心确诊的1277例0～6岁永久性听力损失儿童的临床资料,根据是否接受新生儿听力筛查及筛查结果分为三组:筛查未通过组、筛查通过组及未筛查组,分析患儿的确诊年龄及发现途径.结果 1277例听力损失患儿中,筛查未通过组1005例(78.70％),确诊的中位年龄为4个月;筛查通过组96例(7.52％),确诊的中位年龄为21.5个月;未筛查组176例(13.78％),确诊的中位年龄为24.5个月.筛查未通过组的听力损失确诊年龄明显早于筛查通过组和未筛查组(P<0.01);筛查通过组与未筛查组之间差异无统计学意义(P>0.05).1277例中,发现途径主要为新生儿听力筛查(78.70％,1005/1277);筛查通过组96例中,主要通过家人对其听觉和言语发育观察发现(66.67％,64/96),其次为耳聋基因筛查阳性转诊(11.46％,11/96)和入园体检发现(7.29％,7/96);未筛查组176例中,主要通过家人对其听觉和言语发育观察发现(98.29％,173/176).结论 新生儿听力筛查是早期发现永久性听力损失患儿的主要途径,使患儿确诊年龄明显提前,而筛查通过组和未筛查组确诊年龄仍然较晚.

In order to investigate the genetic causes of hearing loss in a Chinese proband (in Family A) with enlarged vestibular aqueduct (EVA) and to investigate the genotype of two Chinese probands with SLC26A4 singe-allelic mutation and normal hearing (in Families B and C, respectively), the three probands and their parents were clinically and genetically evaluated. Twenty exons and flanking splice sites of the SLC26A4 gene were screened for pathogenic mutations via amplification with PCR and bidirectional sequencing. As controls, a group of 400 healthy newborns from the same ethnic background underwent SLC26A4 gene screening using the same method. The three probands all harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. The genotypes of mutations in Families A, B, and C are c.1211C>A/c.919-2A>G, c.1729G>A/c.919-2A>G, and c.1286C>A/c.919-2A>G, respectively. The missense mutations c.1211C>A (p.T430Q) in exon 10 and c.1729G>A (p.V577I) in exon 16 are both reported for the first time and were absent in 400 healthy newborns. c.1211C>A has Glutamine (Gln) at amino acid 430 instead of Threonine (Thr), and c.1729G>A has Isoleucine (Ile) at amino acid 577 instead of Valine (Val). c.1286C>A, a mutation previously reported in DVD and HGMD, was associated with Mondini deformity, but a proband with the c.1286C>A mutation in this study was normal. This study has demonstrated that the novel missense mutation c.1211C>A in compound heterozygosity with c.919-2A>G in the SLC26A4 gene is likely to be the cause of deafness in Family A. A novel variant, c.1729G>A, was identified and is likely benign. The pathogenicity of the c.1286C>A mutation warrants more in-depth study. These findings will broaden the spectrum of known SLC26A4 mutations in the Chinese population, providing more information for genetic counseling and diagnosis of hearing loss with EVA.

目的 分析北京地区大样本新生儿耳聋基因筛查的突变情况、纯合/复合杂合突变者(确诊者)的听力学特点及干预情况.方法 研究对象为2012年4月～2014年4月在北京地区出生的新生儿75649例,均接受了新生儿耳聋基因筛查,包括4基因9个位点:GJB2基因(c.35delG、c.176191del16、c.235delC、c.299300delAT)、SLC26A4基因(c.919-2A>G、c.2168A>G)、线粒体12SrRNA基因(m.1555A>G、m.1494C>T)和GJB3基因(c.538C>T).分析阳性检出率及等位基因检出率,并对纯合/复合杂合突变者(确诊者)进行随访,分析新生儿听力筛查结果、听力损失程度,干预时间及干预效果.结果 总体阳性检出率4.51％(3412/75649),其中GJB2基因最高,为2.419％(1830/75649),其次由高到低分别为SLC26A4基因1.520％(1150/75649)、GJB3基因0.328％(248/75649)、线粒体12SrRNA 0.184％(139/75649)及双基因杂合突变0.059％(45/75649).关于等位基因突变检出率,GJB2基因中c.235delC最高,为0.91％(1380/151298),SLC26A4基因中c.919-2A>G最高,为0.67％(1010/151298).对纯合/复合杂合突变者17例进行随访,成功15例,失访2例.成功的15例中,新生儿听力筛查双耳未通过占80％(12/15),双耳通过为20％(3/15);15例均为感音神经性听力损失,其中重度及极重度66.67％(10/15),中度20％(3/15),轻度13.33％(2/15).15例中接受听力干预13例,助听器初次干预月龄中位数为6个月,人工耳蜗干预月龄中位数为18个月.15例中就读于正常小学或正常幼儿园14例(93.33％).结论 本研究的主要突变基因为GJB2基因及SLC26A4基因;c.235delC和c.919-2A>G为主要突变位点.新生儿耳聋基因筛查确诊者均有不同程度的听力损失,早期干预效果好,提示新生儿耳聋基因筛查值得推广;新生儿听力筛查通过的耳聋基因筛查确诊者,尤其需要临床关注.

目的 分析GJB2基因p.V37I(c.109G>A)位点突变儿童的临床听力学特点,探讨p.V37I杂合突变的临床意义,为遗传咨询提供临床依据.方法 研究对象为2012年至2018年,于我院儿童听力诊断中心就诊,确诊为c.235delC/p.V37I、c.299delAT/p.V37I及c.176del16/p.V37I复合杂合突变的儿童41人.所有儿童均接受新生儿听力筛查、耳聋基因芯片筛查和GJB2基因全编码区检测;同时接受声导抗、畸变产物耳声发射、听性脑干反应、多频稳态诱发电位和小儿行为测听等听力学检测.结果 41例中,男26例、女15例,平均首诊年龄:5.3±4.0个月.常见基因型为c.235delC/p.V37I复合杂合突变,共25例(61.0％).新生儿听力筛查通过13例(31.7％),未通过28例(68.3％).4例通过新生儿听力筛查,之后确诊为轻度听力损失,7例未通过新生儿听力筛查,之后确诊为听力正常.听力诊断正常16例(39.0％),听力损失25例(61.0％),其中,轻度14例(56.0％,14/25)、中度11例(44.0％,11/25).c.235delC/p.V37I突变儿童,52.0％出现听力损失(13/25),以轻度为主.c.299delAT/p.V37I突变儿童,77.3％(10/13)出现听力损失,以中度为主.结论 本组GJB2基因p.V37I杂合突变儿童,基因型以c.235delC/p.V37I为主,约39.0％(16/41)表现为听力正常,61.0％(25/41)出现轻-中度听力损失.4例儿童通过新生儿听力筛查,之后出现听力损失,提示GJB2基因p.V37I突变与迟发性听力损失相关.基因型为c.299delAT/p.V37I的儿童出现听力损失可能性较大,临床应予以重视.

Objective: To analyze the auditory follow-up alteration of GJB2 associated hearing loss children. Method: Forty three children aged 0-5 years with homozygous or heterozygous mutations of gene attach to the Children' s Hearing Diagnostic Center of our hospital were enrolled in this study. Distortion product otoacoustic emissions and acoustic immittance, auditory brainstem response, auditory steady state response, acoustic impedance, pediatric behavior audiometry and other audiological tests were performed. The subjects had at least two audiology diagnosis results at different time; follow-up time was at least three months. According to the genotype, the subjects were divided into two groups: 23 cases(53.49%) in the truncating mutation/truncating mutation (T/T) group and 20 cases(46.51%) in the nontruncating mutation/truncating mutation (NT/T) group. Hearing levels of the first and last diagnoses and progression rate were compared between the two groups, and the progression value and progression rate were analyzed. Result: The average follow-up time was(19.63 ± 16.76) months. The frequency of c. 235delC (56.98%) in GJB2 gene mutations sites was highest in this group, followed by c. 109G> A (22.09%). The first diagnosis of hearing loss, T/T group was mainly severe(60.87%), NT/T group was mainly mild (50.00%); The degree of final hearing loss in the T/T group was mainly severe(50.00%) while the NT/T group was mainly mild(42.50%), and the T/T group was both heavier than the NT/T group. The difference was both statistically significant. Follow-up research on 43 cases(86 ears) showed that 3 cases(4 ears) developed hearing progression, 1 of them were bilateral progression, two was unilateral progression; the overall rate of progression was 4.65%(4/86), and the rate of progression in the T/T group was 2.17%(1/46) while the NT/T group was 7.50%(3/40). There was no significant difference between the two groups. The average progression of 4 ears was 11.25 dB HL, the average progression speed was 0.5 dB HL/month. Conclusion: This study showed that the degree of hearing loss of associated hearing loss children was mild to profound, and those with truncating mutations/truncating mutations were severer than those with nontruncating mutations/truncating mutations. Hearing progression was seen in both groups, it is suggested that children with GJB2 gene mutations hearing progression may occur during growth and development, therefore, they should be followed up regularly. .

Noise can cause multi-system damage, of which permanent damage to the auditory system is the most serious and about 5％-12％ of the world's population exhibit varying degrees of noise. In the early stage of noise damage could cause mild tinnitus, hidden hearing loss or temporary high frequency hearing loss; as the increase of noise exposure time of, tinnitus and hearing loss aggravated, resulting in permanent hearing loss, meanwhile, can cause increase of speech recognition threshold and decrease of speech recognition score; some patients may also have symptoms such as insomnia, anxiety, dizziness, and headache. Therefore, early screening of people exposed to noise is important. Analyze the research overview related that, then classify the early screening technique of noise-induced hearing loss into DPOAE test, high frequency pure tone audiometry, speech audiometry, internet screening, tinnitus assessment, mental health level assessment and susceptibility gene screening, which provides a reference for clinical applications.

Objectives: To identify second-allele variant in infants with a known single-allele mutation of the SLC26A4 gene and to determine the frequency of their occurrence; and to investigate the clinical audiological characteristics of infants with bi-allelic mutations in SLC26A4. Methods: The study subjects were 371 patients with a single-allele SLC26A4 mutation detected by neonatal deafness gene screening (4 genes and 9 pathogenic variants) who were treated at the otology outpatient department of Beijing Tongren Hospital. The exonic and flanking splice site regions of the SLC26A4 gene were sequenced for all patients. All patients with bi-allelic SLC26A4 mutations underwent audiological evaluation, and some also underwent temporal bone computed tomography and/or inner ear magnetic resonance imaging. Results: Of the 371 patients, 314 (84.64%) had an c.919-2A > G heterozygous mutation and 57 (15.36%) had a c.2168A > G (p.H723R) heterozygous mutation. 13 patients (3.50%) had a second-allele variant, including 11 (2.96%) with pathogenic mutations and 1 (0.27%) with a likely benign variant. Of the 13 patients with bi-allelic mutations, 11 had hearing loss and 2 had normal hearing, the latter of whom had c.919-2A > G/c.1766A > G and c.919-2A > G/c.757A > G compound heterozygous mutations, respectively. Four of the 13 patients with bi-allelic mutations had passed the universal newborn hearing screening, including 2 cases (15.38%) with hearing loss. The most prevalent degree of hearing loss was profound (40.91%), followed by severe (36.36%). The most prevalent audiometric configuration was sloping hearing loss (50.00%), followed by flat-type hearing loss (40.91%). Conclusions: This is the first report in China of the frequency of occurrence of second-allele variant in infants with a known single-allele mutation of the SLC26A4 gene; the frequency was 3.50% for any type of variant and 2.96% for pathogenic mutations. A novel variant, c.1766A > G (p.Q589R), which is likely benign, was identified. The pathogenicity of c.757A > G (p.I253V) mutation deserves more in-depth research. For infants with bi-allelic SLC26A4 mutations, the degree of hearing loss was mainly severe-to-profound and the audiometric configuration was mainly sloping.

Objective:To explore the correlation of SLC26A4 genotype and audiology.Method:The subjects were 70 children aged 0 to 7 years old, who were admitted to otological outpatient department.All subjects received nine crystal hereditary deafness gene chip and confirmed by (or)SLC26A4 gene full coding region detection.The patients were diagnosed as homozygous or compound heterozygous mutations.At the same time,acoustic immittance,auditory brainstem response, auditory steady state response and pediatric behavior audiometry, newborn hearing screening and other audiological tests were displayed. According to the genotype, the subjects were divided into two groups: group A (SLC26A4 gene homozygous mutation) in 40 cases, group B (SLC26A4 gene compound heterozygous mutation) in 30 cases. The frequency of SLC26A4 gene mutation, the two groups of genotypes and hearing screening results,the degree of hearing loss and audiometric configurations were analyzed statistically. Result: In 70 patients, the top 4 of the 70 patients with high frequency of mutations were IVS7-2A> G(76.43%), 2168A> G(15.00%), 1226G> A(2.86%) and 2000T> C(2.16%), respectively. 34.29% of newborns passed hearing screening with single or double ears, among which group A and group B were 32.50% and 36.67%,respectively. There was no statistically significant difference between two groups in hearing screening. The degree of hearing loss in group A(56.25%) and group B(48.33%) were mainly profound and there was no significant difference between them. The audiometric configurations: group A(60.00%) was mainly high frequency loss type, while group B(55.00%) was mainly flat type. The difference between them was statistically significant.Conclusion:The mutation sites of SLC26A4 gene were mainly IVS7-2A> G, and the degree of hearing loss was mostly profound. To the audiometric configurations,SLC26A4 gene homozygous mutant were mainly high frequency loss type, while SLC26A4 gene compound heterozygous mutant were mainly flat type. 34.29% children passed universal newborn hearing screening with one ear at least, which indicates SLC26A4 gene mutations can result in late-onset hearing loss, so those patients should be attached great importance..

The current study retrospectively investigated variations in audiological phenotypes in children with GJB2 gene mutations. Subjects were 128 infants and young children who were seen as outpatients by Otology at Beijing Tongren Hospital from 2012 to 2018. Of the 128 subjects, 99 had biallelic truncating (T/T) mutations and 29 had truncating/nontruncating (T/NT) mutations. Genotypes, results of universal newborn hearing screening (UNHS), and the degree and symmetry of hearing loss were examined in the two groups. Twenty-two subjects (20.37%, 22/128) passed UNHS, including 13 children with T/T mutations and 9 with T/NT mutations. Of the 128 subjects, 22 had normal hearing, 2 had unilateral hearing loss, and 115 had bilateral hearing loss. Severe-to-profound hearing loss was the most prevalent phenotype in children with T/T mutations (73.23%), while normal hearing was prevalent in children with T/NT mutations (41.38%). Symmetrical hearing loss was the main phenotype in both groups, and the number of subjects with symmetrical hearing loss did not differ significantly between the two groups. Therefore, children with GJB2 gene mutations have phenotypic variability in terms of their results of UNHS and their degree and symmetry of hearing loss. Subjects with T/NT mutations of the GJB2 gene were more likely to pass UNHS and had milder hearing loss compared to those with T/T mutations. Symmetrical hearing loss was the main phenotype in the two groups, but 36.53% of children had bilateral asymmetric hearing loss. Parents of all subjects with sensorineural hearing loss were informed that their children may have a GJB2 mutation.

GJB2 gene is the commonest causative gene for autosomal recessive nonsyndromic hearing loss. The detection rate of GJB2 gene p.V37I mutation in Han Chinese hearing loss populations was higher than in the normal hearing populations. The p.V37I mutation is mainly associated withmild to moderate, delayed-onset and progressivehearing loss with a low penetrance rate of approximately 17％ in the Chinese Han population. This paper reviews the clinical audiological characteristics of the p.V37I mutation in GJB2 gene, which can provide reference for clinical deafness gene diagnosis and genetic counseling.

Objective:To investigate the clinical audiological characteristics of twins and analyze the risk factors for hearing loss. Method：The subjects were 72 cases,selected from our hospital otological outpatient of 0 to 4 years old twins. All subjects underwent universal newborn hearing screening and had definite results. At the same time, acoustic immittance,auditory brainstem response, auditory steady-state response, pediatric behavior audiometry and other audiological tests were carried out. Subjects were divided into two groups according to whether with high risk factors for hearing loss: 42 patients(58.33%) in group A(risk factor group) and 30 patients(41.67%) in group B (no risk factor group).The results of universal newborn hearing screening(UNHS),hearing diagnosis, degree of hearing loss, type of hearing curve and risk factors categories of hearing loss were analyzed for both groups of subjects.Result:In 72 cases,41 were males and 31 were females. Thirty-one were the first born and 41 were the second born. Age distribution of first visit:3 to 40 months, median age: 4-6 months.Forty-seven(65.27%) failed in the UNHS. The failing rate was higher in group A(76.19%) than in group B(50.00%).Fifty(69.44%) were diagnosed with hearing loss.78.57% of hearing loss was diagnosed in group A, which was higher than that in group B(56.67%).The degree of hearing loss in group A was mainly profound(43.55%) and group B was moderate(48.00%).The differences above all was statistically significant.For the hearing curve type, group A(35.48%) and group B(40.00%) were both mainly flat-type, the difference was not statistically significant. In 72 cases, there were 42 cases(58.33%) with risk factors for hearing loss, of which 38.1% had two or more kinds of risk factors and 61.9% had one kind of risk factor.Hyperbilirubinemia was the major risk factor(34.92%).Conclusion:69.44% of twins had a confirmed hearing loss. Those with risk factors had higher failing rate of UNHS and more serious hearing loss.58.33% of twins had risk factors for hearing loss, and individuals with two or more kinds of risk factors were much more. Hyperbilirubinemia takes the first place and should be paid enough attention by clinicians.

In order to investigate the genetic causes of hearing loss in a Chinese proband with nonsyndromic hearing loss and enlarged vestibular aqueduct (EVA), we conducted clinical and genetic evaluations in a deaf proband and her parents with normal hearing. 20 exons and flanking splice sites of the SLC26A4 gene were screened for pathogenic mutations by PCR amplification and bidirectional sequencing. As a control, a group of 400 healthy newborns from the same ethnic background were subjected to SLC26A4 gene screening using the same method. The proband harbored two mutations in the SLC26A4 gene in the form of compound heterozygosity. She was found to be heterozygous for a novel mutation c.574delC (p.Leu192Ter) in exon 5 and for the known mutation c.919-2A>G(c.IVS7-2A>G). Her mother was a heterozygous carrier of the c.919-2A>G mutation, and her father was a heterozygous carrier of the c.574delC and therefore co-segregated with the genetic disease. The c.574delC mutation was absent in 400 healthy newborns. The frameshift mutation causes the leucine (Leu) at amino acid position 192 to become a termination codon, leading to termination of protein sequence coding. This study demonstrates that the novel frameshift mutation c.574delC (p.Leu192Ter) in compound heterozygosity with c.919-2A>G in the SLC26A4 gene is the main cause of deafness in a family. Our study will expand the spectrum of known SLC26A4 mutations in the Chinese population, providing more information on genetic counseling, and diagnosis in hearing loss with EVA.