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Hearing Disorders: HELP
Articles by Tao Yang
Based on 43 articles published since 2009
(Why 43 articles?)
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Between 2009 and 2019, Tao Yang wrote the following 43 articles about Hearing Disorders.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Diagnosis, Intervention, and Prevention of Genetic Hearing Loss. 2019

Yang, Tao / Guo, Luo / Wang, Longhao / Yu, Xiaoyu. ·Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. yangtfxl@sina.com. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. yangtfxl@sina.com. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. yangtfxl@sina.com. · Key Laboratory of Hearing Medicine of NHFPC, ENT Institute and Otorhinolaryngology Department, Shanghai Engineering Research Centre of Cochlear Implant, Affiliated Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. ·Adv Exp Med Biol · Pubmed #30915702.

ABSTRACT: It is estimated that at least 50% of congenital or childhood hearing loss is attributable to genetic causes. In non-syndromic hearing loss, which accounts for 70% of genetic hearing loss, approximately 80% of cases are autosomal recessive, 15% autosomal dominant, and 1-2% mitochondrial or X-linked. In addition, 30% of genetic hearing loss is syndromic. The genetic causes of hearing loss are highly heterogeneous. So far, more than 140 deafness-related genes have been discovered. Studies on those genes tremendously increased our understanding of the inner ear functions at the molecular level. It also offers important information for the patients and allows personalized and accurate genetic counseling. In many cases, genetic diagnosis of hearing loss can help to avoid unnecessary and costly clinical testing, offer prognostic information, and guide future medical management. On the other hand, a variety of gene therapeutic approaches have been developed aiming to relieve or converse the hearing loss due to genetic causes. Prevention of genetic hearing loss is feasible through prepregnancy and prenatal genetic diagnosis and counseling.

2 Review [Genetic research of age-related hearing impairment]. 2013

Luo, Hua-jie / Yang, Tao / Wu, Hao. · ·Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #23656826.

ABSTRACT: -- No abstract --

3 Article A Novel p.G141R Mutation in 2018

Wang, Xueling / Wang, Longhao / Peng, Hu / Yang, Tao / Wu, Hao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. · Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China. ·Neural Plast · Pubmed #29849566.

ABSTRACT: Genetic hearing impairment is highly heterogeneous. In this study, targeted next-generation sequencing (NGS) in two Chinese Han families identified a novel p.G141R homozygous mutation in

4 Article Carrier re-sequencing reveals rare but benign variants in recessive deafness genes. 2017

He, Longxia / Pang, Xiuhong / Chen, Penghui / Wang, Xiaowen / Yang, Tao / Wu, Hao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. yangtfxl@sina.com. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. yangtfxl@sina.com. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. yangtfxl@sina.com. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. yangtfxl@sina.com. · Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. wuhao622@sina.cn. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. wuhao622@sina.cn. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. wuhao622@sina.cn. ·Sci Rep · Pubmed #28900111.

ABSTRACT: For recessive Mendelian disorders, determining the pathogenicity of rare, non-synonymous variants in known causative genes can be challenging without expanded pedigrees and/or functional analysis. In this study, we proposed to establish a database of rare but benign variants in recessive deafness genes by systematic carrier re-sequencing. As a pilot study, 30 heterozygous carriers of pathogenic variants for deafness were identified from unaffected family members of 18 deaf probands. The entire coding regions of the corresponding genes were re-sequenced in those carriers by targeted next-generation sequencing or Sanger sequencing. A total of 32 non-synonymous variants were identified in the normal-hearing carriers in trans with the pathogenic variant and therefore were classified as benign. Among them were five rare (minor allele frequencies less than 0.005) variants that had previously undefined, disputable or even misclassified function: p.A434T (c.1300 G > A) in SLC26A4, p.R266Q (c.797 G > A) in LOXHD1, p.K96Q (c.286 A > C) in MYO15A, p.T123N (c.368 C > A) in GJB2 and p.V1299I (c.797 G > A) in CDH23. Our results suggested that large scale carrier re-sequencing may be warranted to establish a database of rare but benign variants in causative genes in order to reduce false positive genetic diagnosis of recessive Mendelian disorders.

5 Article Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: Potential pathogenic mechanism. 2017

Zhou, Xiao-Long / He, Long-Xia / Yu, Li-Jia / Wang, Yong / Wang, Xi-Jin / Wang, En-Duo / Yang, Tao. ·State Key Laboratory of Molecular Biology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Chengdu Integrated TCM & Western Medicine Hospital, Sichuan Province, China. · Department of Neurology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. · School of Life Science and Technology, Shanghai Tech University, Shanghai, China. ·Hum Mutat · Pubmed #28887846.

ABSTRACT: Leukoencephalopathies are a broad class of common neurologic deterioration for which the etiology remains unsolved in many cases. In a Chinese Han family segregated with sensorineural hearing loss and leukoencephalopathy, candidate pathogenic variants were identified by targeted next-generation sequencing of 144 genes associated with deafness and 108 genes with leukoencephalopathy. Novel compound heterozygous mutations p.R477H and p.P505S were identified in KARS, which encodes lysyl-tRNA synthetase (LysRS), as the only candidate causative variants. These two mutations were functionally characterized by enzymatic assays, immunofluorescence, circular dichroism analysis, and gel filtration chromatography. Despite no alteration in the dimer-tetramer oligomerization and cellular distribution by either mutation, the protein structure was notably influenced by the R477H mutation, which subsequently released the protein from the multiple-synthetase complex (MSC). Mutant LysRSs with the R477H and P505S mutations had decreased tRNA

6 Article Association of leukocyte telomere length and the risk of age-related hearing impairment in Chinese Hans. 2017

Liu, Han / Luo, Huajie / Yang, Tao / Wu, Hao / Chen, Dan. ·Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. · Department of Otolaryngology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. yangtfxl@sina.com. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. yangtfxl@sina.com. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. yangtfxl@sina.com. · Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. wuhao622@sina.cn. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. wuhao622@sina.cn. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. wuhao622@sina.cn. · Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China. simpledandan1981@163.com. ·Sci Rep · Pubmed #28860610.

ABSTRACT: Age-related hearing loss (ARHI) is the most common sensory disorder in the elderly. Although telomere attrition has been shown as a determinant in the pathobiology of various age-related diseases, it remains unknown whether telomere length is associated with ARHI. We hypothesized that decreased leukocyte telomere length (LTL) increased the risk of ARHI. Thus, we measured LTL of 666 ARHI and 43 controls by an established quantitative PCR technique. Four audiogram shape subtypes of ARHI, including "flat shape (FL)", "2-4 kHz abrupt loss (AL) shape", "8 kHz dip (8D) shape" and "sloping shape (SL)" could be identified among the cases using K-means cluster analysis. Longer LTL was associated with the reduced incidence of ARHI (adjusted OR = 0.550, 95% CI: 0.420-0.721, P < 0.0001 for all the ARHI; 0.498, 0.318-0.780, P = 0.0023 for FL subgroup; 0.428, 0.292-0.628, P < 0.0001 for AL subgroup; 0.552, 0.399-0.764, P = 0.0003 for mSL subgroup). Subjects in the highest tertile of LTL were at less risk for ARHI than those in the lowest and middle tertiles (OR for ARHI: 0.327, 95% CI 0.170-0.629, P = 0.0008). There was a descending trend of LTL as the degree of pure tone threshold average (PTA) aggravated. These results suggest that telomere attrition may be involved in the progression of ARHI.

7 Article A comparison between systemic and intratympanic steroid therapies as initial therapy for idiopathic sudden sensorineural hearing loss: a meta-analysis. 2017

Qiang, Qingfen / Wu, Xuewen / Yang, Tao / Yang, Chunguang / Sun, Hong. ·a Department of Otolaryngology Head and Neck Surgery , Xiangya Hospital, Central South University , Changsha , Hunan , PR China. · b Province Key Laboratory of Otolaryngology Critical Diseases , Xiangya Hospital, Central South University , Changsha , Hunan , PR China. · c Department of Otolaryngology Head and Neck Surgery , the Second Xiangya Hospital of Central South University , Changsha , Hunan , PR China. ·Acta Otolaryngol · Pubmed #27921520.

ABSTRACT: CONCLUSIONS: Intratympanic steroid (ITS) treatment groups exhibited better outcomes in PTA improvement and recovery rate than systemic steroid therapy (SST) groups. Whether initial hearing loss severity would influence the PTA improvement and recovery rate still requires further research. OBJECTIVE: This article was aimed at evaluating whether intratympanic steroid (ITS) treatment would provide benefits over systemic steroid therapy (SST) as initial therapy in patients with idiopathic sudden sensorineural hearing loss (ISSHL). A meta-analysis was carried out based on published RCTs that included the hearing outcomes of ITS treatment and SST in ISSHL as initial therapy. Both PTA differences and recovery rate were analyzed. METHODS: The literature search was based on the online database including Pubmed, Embase, and Cochrane trails, which completed in July 2016. This study extracted the relevant data following the selection criteria. Mean difference (MD) of PTA differences and Odds ratio (OR) of recovery rate were calculated within 95% confidence intervals. RESULTS: Six eligible articles were reviewed. The pooled MDs of PTA differences was 3.42 (95% CI = 0.17-6.67, p = .04) and the pooled ORs of recovery rate was 2.05 (95% CI = 1.38-3.03, p = .0003), which indicated that ITS treatment yielded better PTA improvement than SST. Sub-group analyses based on the initial hearing loss were also conducted; however, the difference was insignificant according to our analysis results (p = .82 for PTA improvement and p = .26 for recovery rate).

8 Article The role of Efr3a in age-related hearing loss. 2017

Hu, Haixia / Ma, Yan / Ye, Bin / Wang, Quan / Yang, Tao / Lv, Jingrong / Shi, Jun / Wu, Hao / Xiang, Mingliang. ·Department of Otolaryngology & Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200092, China. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200092, China. · Department of Otolaryngology & Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200092, China. Electronic address: mingliangxiang@163.com. ·Neuroscience · Pubmed #27867060.

ABSTRACT: Efr3a has been found to be involved in the functional maintenance and structural degeneration of sensory and motor nervous tissues. Our previous data have suggested that Efr3a may be associated with the initiation of the degeneration of spiral ganglion neurons (SGNs). In this study, we used Efr3a knockdown (Efr3a KD) and Efr3a overexpression (Efr3a OE) mice to determine the role of Efr3a in age-related hearing loss. Measurements of hearing thresholds showed that Efr3a had little or no influence on the hearing threshold at all frequencies in adult mice, whereas in an early stage of senescence, Efr3a reduction resulted in better hearing function, especially at 10 and 12months of age. No significant differences were observed in hair cell loss among the three groups until 14months. The number of surviving hair cells in the OE mice was lower than that in the KD mice. As indicated by the density of SGNs in the upper basal turn, the Efr3a OE mice displayed earlier and more severe degeneration than the KD mice. In addition, the p-Akt levels in the cochlear spiral ganglions were higher in adult Efr3a KD mice than in WT and OE mice, although there was no difference in Akt expression among the three groups. Our study suggests that down-regulation of Efr3a might improve hearing function and alleviate the degeneration of SGNs in an early stage of senescence, probably via enhancing the basal expression of activated Akt.

9 Article A dominant variant in DMXL2 is linked to nonsyndromic hearing loss. 2017

Chen, Dong-Ye / Liu, Xing-Feng / Lin, Xiao-Jiang / Zhang, Dan / Chai, Yong-Chuan / Yu, De-Hong / Sun, Chang-Ling / Wang, Xue-Ling / Zhu, Wei-Dong / Chen, Ying / Sun, Lian-Hua / Wang, Xiao-Wen / Shi, Fu-Xin / Huang, Zhi-Wu / Yang, Tao / Wu, Hao. ·Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · State-Key Laboratory of Biomembrane and Membrane Engineering, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China. · Department of Otolaryngology, People's Hospital of Kaihua, Kaihua, China. · Department of Otolaryngology Head and Neck Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China. ·Genet Med · Pubmed #27657680.

ABSTRACT: PURPOSE: To explore the genetic etiology of deafness in a dominant family with late-onset, progressive, nonsyndromic hearing loss. METHODS: Genome-wide linkage analysis was performed for 21 family members. Candidate pathogenic variants were identified by whole-exome sequencing of selected family members and confirmed by Sanger sequencing of all family members. Cochlear expression of Dmxl2 was investigated by reverse-transcription polymerase chain reaction (RT-PCR) and immunostaining of the organ of Corti from mice. RESULTS: The causative gene was mapped to a 9.68-Mb candidate region on chromosome 15q21.2 (maximum logarithm of the odds score = 4.03) that contained no previously described deafness genes. Whole-exome sequencing identified heterozygous c.7250G>A (p.Arg2417His) in DMXL2 as the only candidate pathogenic variant segregating the hearing loss. In mouse cochlea, expression of DMXL2 was restricted to the hair cells and the spiral ganglion neurons. CONCLUSION: Our data indicated that the p.Arg2417His variant in DMXL2 is associated with dominant, nonsyndromic hearing loss and suggested an important role of DMXL2 in inner ear function.Genet Med advance online publication 22 September 2016.

10 Article Mutation in the Hair Cell Specific Gene 2016

He, Longxia / Pang, Xiuhong / Chen, Penghui / Wu, Hao / Yang, Tao. ·Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. ·Neural Plast · Pubmed #28053790.

ABSTRACT: Autosomal dominant nonsyndromic hearing loss (ADNSHL) is extremely heterogeneous. So far the genetic etiological contribution of the gene

11 Article None 2016

Chen, Penghui / He, Longxia / Pang, Xiuhong / Wang, Xiaowen / Yang, Tao / Wu, Hao. ·Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. ·Neural Plast · Pubmed #27965898.

ABSTRACT: Nonsyndromic deafness is genetically heterogeneous but phenotypically similar among many cases. Though a variety of targeted next-generation sequencing (NGS) panels has been recently developed to facilitate genetic screening of nonsyndromic deafness, some syndromic deafness genes outside the panels may lead to clinical phenotypes similar to nonsyndromic deafness. In this study, we performed comprehensive genetic screening in a dominant family in which the proband was initially diagnosed with nonsyndromic deafness. No pathogenic mutation was identified by targeted NGS in 72 nonsyndromic and another 72 syndromic deafness genes. Whole exome sequencing, however, identified a p.E313K mutation in

12 Article Characterization of a knock-in mouse model of the homozygous p.V37I variant in Gjb2. 2016

Chen, Ying / Hu, Lingxiang / Wang, Xueling / Sun, Changling / Lin, Xin / Li, Lei / Mei, Ling / Huang, Zhiwu / Yang, Tao / Wu, Hao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Ear Institute, Shanghai Jiaotong University, Shanghai, China. · Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. ·Sci Rep · Pubmed #27623246.

ABSTRACT: The homozygous p.V37I variant in GJB2 is prevalent in East and Southeast Asians and may lead to mild-to-moderate hearing loss with reduced penetrance. To investigate the pathogenic mechanism underlying this variant, we generated a knock-in mouse model of homozygous p.V37I by an embryonic stem cell gene targeting method. Auditory brainstem response test showed that the knock-in mice developed progressive, mild-to-moderate hearing loss over the first 4-9 months. Overall no significant developmental and morphological abnormality was observed in the knock-in mouse cochlea, while confocal immunostaining and electron microscopic scanning revealed minor loss of the outer hair cells. Gene expression microarray analysis identified 105 up-regulated and 43 down-regulated genes in P5 knock-in mouse cochleae (P < 0.05 adjusted by the Benjamini &Hochberg method), among which four top candidate genes with the highest fold-changes or implication to deafness Fcer1g, Nnmt and Lars2 and Cuedc1 were verified by quantitative real-time PCR. Our study demonstrated that the homozygous p.V37I knock-in mouse modeled the hearing phenotype of the human patients and can serve as a useful animal model for further studies. The differentially expressed genes identified in this study may shed new insights into the understanding of the pathogenic mechanism and the phenotypic modification of homozygous p.V37I.

13 Article Attitudes toward carrier screening and prenatal diagnosis for recessive hereditary deafness among the educated population in urban China. 2016

Fu, Xiaoli / Cai, Yi / Hu, Yechen / Liu, Jisheng / Yang, Tao. ·Depatment of Hydraulic Engineering, School of Civil Engineering, Tongji University, Shanghai, China. · High School Affiliated to Fudan University, Shanghai, China. · Department of Otorhinolaryngology, First Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai, China. ·Am J Med Genet A · Pubmed #27511314.

ABSTRACT: Approximately 80% of hereditary deafness is recessive, in which case most mutation carriers were unaware of their carrier status. Though parental attitudes toward genetic testing and prenatal diagnosis are overall positive in those with deaf children, there is little information about that in the general population. To this end, we designed a self-completed questionnaire and distributed it in two colleges in Shanghai, China. A total of 975 completed surveys were returned in print or online forms. Our results showed that 98.7% of the respondents without family history of early onset deafness did not know or underestimated their likelihood to carry a recessive mutation in common deafness genes. After brief written information was given using GJB2, the most common recessive deafness gene as the example, 67.7% of the respondents expressed interest in knowing if they are carriers of GJB2 mutations through genetic testing. In hypothetical circumstance of carrying a recessive GJB2 mutation, 86.9% would suggest their partners to also take the test. In case that both were carriers, 88.7% would consider prenatal diagnosis and 80.7% would consider terminating an affected pregnancy. On the basis of these results, it was concluded that despite the poor awareness to the risk of recessive hereditary deafness, the majority of the educated population in urban China likely hold a positive view toward carrier screening and prenatal diagnosis of recessive deafness genes. © 2016 Wiley Periodicals, Inc.

14 Article The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population. 2016

Luo, Huajie / Wu, Hao / Shen, Hailian / Chen, Haifeng / Yang, Tao / Huang, Zhiwu / Jin, Xiaojie / Pang, Xiuhong / Li, Lei / Hu, Xianting / Jiang, Xuemei / Fan, Zhuping / Li, Jiping. ·Department of Otolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road Pudong New Area, Shanghai, 200127, People's Republic of China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China. · Ear Institute, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China. · Renji-Med X Clinical Stem Cell Research Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China. · Shanghai Center for Bioinformation Technology, Shanghai, 200235, People's Republic of China. · Department of Bioinformatics and Biostatistics, College of Life Sciences and Biotechnology, Shanghai Jiaotong University, Shanghai, 200240, People's Republic of China. · Health Check-up Center, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China. · Health Check-up Center, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China. · Department of Otolaryngology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, 160 Pujian Road Pudong New Area, Shanghai, 200127, People's Republic of China. drlijiping@163.com. ·Eur Arch Otorhinolaryngol · Pubmed #26187738.

ABSTRACT: This study aimed to test the association between the European GWAS-identified risk IQGAP2 SNP rs457717 (A>G) and age-related hearing impairment (ARHI) in a Han male Chinese (HMC) population. A total of 2420 HMC subjects were divided into two groups [group 70+: >70 years (n = 1306), and group 70-: ≤70 years (n = 1114)]. The participants were categorised into case and control groups according to Z high scores for group 70- and the severity of hearing loss and different audiogram shapes identified by K-means cluster analysis for group 70+. The IQGAP2 tagSNP rs457717 was genotyped in accordance with the different ARHI phenotypes. The genotype distributions of IQGAP2 (AA/AG/GG) were not significantly different between the case and control groups (P = 0.613 for group 70-; P = 0.602 for group 70+). Compared with genotype AA, the ORs of genotypes AG and GG for ARHI were not significantly different following adjustment for other environmental risk factors. We demonstrated that the IQGAP2 TagSNP rs457717 (A/G) was not associated with ARHI in HMC individuals.

15 Article A 7666-bp genomic deletion is frequent in Chinese Han deaf patients with non-syndromic enlarged vestibular aqueduct but without bi-allelic SLC26A4 mutations. 2015

Pang, Xiuhong / Chai, Yongchuan / He, Longxia / Chen, Penghui / Wang, Xiaowen / Li, Lei / Jia, Huan / Wu, Hao / Yang, Tao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China; Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China; Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: wuhao622@sina.cn. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: yangtfxl@sina.com. ·Int J Pediatr Otorhinolaryngol · Pubmed #26549381.

ABSTRACT: OBJECTIVES: To investigate the genetic cause of the patients with non-syndromic enlarged vestibular aqueduct (EVA) but without bi-allelic SLC26A4 mutations. METHODS: Presence of a homozygous genomic deletion was detected in a Chinese Han deaf patient (D1467-1) who failed to amplify the first three exons of SLC26A4. The breakpoints of the deletion were fine-mapped and revealed by PCR amplification and sequencing. This deletion was subsequently screened in 22 Chinese Han EVA probands with mono-allelic SLC26A4 mutations. The possible founder effect of the newly identified genomic deletion was evaluated by haplotype analysis. RESULTS: A homozygous c.-2071_307+3801del7666 deletion of SLC26A4 was identified in patient D1467-1. This novel genomic deletion was subsequently identified in 18% (4/22) of the Chinese Han EVA probands with mono-allelic SLC26A4 mutations. Haplotype analysis showed that this genomic deletion is likely a founder mutation in Chinese Hans. CONCLUSION: Our results suggested that the cryptic c.-2071_307+3801del7666 deletion of SLC26A4 is relatively frequent in Chinese Han non-syndromic EVA patients without bi-allelic SLC26A4 mutations. Screening of this genomic deletion should be incorporated into the routine DNA testing of SLC26A4 in Chinese Hans.

16 Article Mutation in PCDH15 may modify the phenotypic expression of the 7511T>C mutation in MT-TS1 in a Chinese Han family with maternally inherited nonsyndromic hearing loss. 2015

Chen, Dong-ye / Zhu, Wei-dong / Chai, Yong-chuan / Chen, Ying / Sun, Lianhua / Yang, Tao / Wu, Hao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200092, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200092, China. Electronic address: yangtfxl@sina.com. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200092, China. Electronic address: wuhao622@sina.cn. ·Int J Pediatr Otorhinolaryngol · Pubmed #26279247.

ABSTRACT: OBJECTIVES: Mutations in MT-TS1 have been found to be associated with nonsyndromic sensorineural hearing loss (SNHL). PCDH15 codes for protocadherin-15, a member of the cadherin superfamily of calcium-dependent cell-cell adhesion molecules. In this study, we analyzed the correlation of both MT-TS1 and PCDH15 mutations in a Chinese Han family segregating maternally inherited nonsyndromic SNHL. METHODS: We ascertained a Chinese Han family segregating maternally inherited nonsyndromic sensorineural hearing loss. Eight of 10 maternal members in this family exhibited late-onset, progressive hearing impairment. Mutation screening of 79 known deafness genes was performed for the proband by targeted next-generation sequencing. RESULTS: A total of 651 variants were detected in this individual. Among them, a homoplasmic 7511T>C variant in MT-TS1, the mitochondrial tRNA (Ser(UCN)) gene, and a heterozygous p.Asp1010Gly variant in PCDH15 were more likely to be pathogenic. Consistent with the matrilineal inheritance with reduced penetrance, the 7511T>C variant in MT-TS1 was found in all 10 maternal members and an additional heterozygous p.Asp1010Gly variant in PCDH15 cosegregated with the hearing loss in this family. CONCLUSION: Our results suggested that the PCDH15 p.Asp1010Gly variant probably modified the phenotypic expression of the 7511T>C mutation in MT-TS1.

17 Article Mono-allelic mutations of SLC26A4 is over-presented in deaf patients with non-syndromic enlarged vestibular aqueduct. 2015

Pang, Xiuhong / Chai, Yongchuan / Chen, Penghui / He, Longxia / Wang, Xiaowen / Wu, Hao / Yang, Tao. ·Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: wuhao622@sina.cn. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. Electronic address: yangtfxl@sina.com. ·Int J Pediatr Otorhinolaryngol · Pubmed #26100058.

ABSTRACT: OBJECTIVES: Recessive mutations of SLC26A4 are the major cause of hearing impairment associated with enlarged vestibular aqueduct (EVA). In a significant percentage of non-syndromic EVA patients, however, only mono-allelic mutations of SLC26A4 can be identified. In this study, we aimed to evaluate whether presence of mono-allelic mutations of SLC26A4 in those patients was coincidental or etiologically associated with the disorder. METHODS: The exons and flanking splicing sites of SLC26A4 were sequenced in 150 Chinese Han deaf probands with non-syndromic EVA. c.919-2A >G and p.H723R, two frequent mutations of SLC26A4 in Chinese Hans, were screened by an allele-specific PCR-based array in 3056 ethnically-matched normal hearing controls. The frequency of mono-allelic c.919-2A >G and p.H723R mutations was determined in each group. The statistical significance of the difference was analyzed by Fisher's exact test. RESULTS: Bi-allelic, mono-allelic and no mutation of SLC26A4 were detected in 98 (65.3%), 18 (12%) and 34 (22.67%) deaf probands with non-syndromic EVA, respectively. The frequency of mono-allelic c.919-2A >G and p.H723R mutations were significantly higher in the 150 deaf probands with non-syndromic EVA (8.67%) than in the 3056 normal hearing controls (1.4%, P=1.8×10(-6)). CONCLUSION: Presence of mono-allelic mutations of SLC26A4 in non-syndromic EVA patients is etiologically associated with this disorder. Additional genetic or environmental causes may be present in those patients and demand further investigation and consideration during the genetic diagnosis and counseling.

18 Article Targeted next-generation sequencing in Uyghur families with non-syndromic sensorineural hearing loss. 2015

Chen, Ying / Wang, Zhentao / Wang, Zhaoyan / Chen, Dongye / Chai, Yongchuan / Pang, Xiuhong / Sun, Lianhua / Wang, Xiaowen / Yang, Tao / Wu, Hao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. ·PLoS One · Pubmed #26011067.

ABSTRACT: The mutation spectrum of deafness genes may vary in different ethnical groups. In this study, we investigated the genetic etiology of nonsyndromic deafness in four consanguineous and two multiplex Uyghur families in which mutations in common deafness genes GJB2, SLC26A4 and MT-RNR1 were excluded. Targeted next-generation sequencing of 97 deafness genes was performed in the probands of each family. Novel pathogenic mutations were identified in four probands including the p.L416R/p.A438T compound heterozygous mutations in TMC1, the homozygous p.V1880E mutation in MYO7A, c.1238delT frameshifting deletion in PCDH15 and c.9690+1G>A splice site mutation in MYO15A. Co-segregation of the mutations and the deafness were confirmed within each family by Sanger sequencing. No pathogenic mutations were identified in one multiplex family and one consanguineous family. Our study provided a useful piece of information for the genetic etiology of deafness in Uyghurs.

19 Article A Novel Missense Mutation of NOG Interferes With the Dimerization of NOG and Causes Proximal Symphalangism Syndrome in a Chinese Family. 2015

Pang, Xiuhong / Wang, Zhaoyan / Chai, Yongchuan / Chen, Hongsai / Li, Lei / Sun, Lianhua / Jia, Huan / Wu, Hao / Yang, Tao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China Department of Otorhinolaryngology-Head and Neck Surgery, Yangzhou University Medical College, Jiangsu Province, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Ear Institute, Shanghai Jiaotong University, Shanghai, China Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China yangtfxl@sina.com wuhao622@sina.cn. ·Ann Otol Rhinol Laryngol · Pubmed #25888563.

ABSTRACT: OBJECTIVES: NOG is an antagonist to bone morphogenetic proteins and plays an important role in proper bone and joint development. Dominant mutations in NOG may lead to a series of symphalangism spectrum disorders. In this study, we aimed to identify the genetic cause and the pathogenic mechanism of an autosomal dominant disorder with cosegregating proximal symphalangism and conductive hearing impairment in a Chinese family. METHODS: Mutation screening of NOG was performed in the affected family members by polymerase chain reaction (PCR) amplification and direct sequencing. Western blotting analysis of NOG was performed in the leukocyte samples of the family members. RESULTS: A novel p.W150C heterozygous mutation in NOG was identified cosegregating with the proximal symphalangism disorder in the family. Western blotting analysis showed that the p.W150C mutation interferes with the dimerization of the mutant NOG. CONCLUSIONS: Our results agreed with previously published results of in vitro studies and suggested that impaired dimerization of mutant NOG is an important pathogenic mechanism for the NOG-related symphalangism spectrum disorder.

20 Article [Diagnosis and prevention of genetic deafness: progress and attention]. 2014

Yang, Tao. · ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #25752101.

ABSTRACT: -- No abstract --

21 Article [Investigation of clinical features and detection of 79 known deafness genes in a large Chinese family with dominant non-syndromic hearing loss]. 2014

Lin, Xiaojiang / Chen, Dongye / Wu, Hao / Yang, Tao / Zhang, Dan / Chai, Yongchuan. ·Department of Otorhinolaryngology, People's Hospital of Kaihua, Zhejiang 324300, China. · Department of Otolaryngology Head and Neck Surgery,Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Jiaotong University Ear Institute, Shanghai 200092, China. Email: wuhao622@sina.cn. ·Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #25351123.

ABSTRACT: OBJECTIVE: To investigate the clinical and genetic characteristics of a large family with late-onset, progressive autosomal dominant non-syndromic hearing loss. METHODS: Collections of detail history hereditary features, physical and audiological examination were performed. After mutation screening of GJB2, SLC26A4, MTRNR1 (12SrRNA) genes by Sanger sequencing, the proband was investigated by targeted next-generation sequencing of 79 deafness genes. RESULTS: This family included seven generations and 73 members. Eleven persons with hearing loss and 11 normal-hearing persons participated in this study. All affected members but one exhibited late-onset, progressive non-syndromic sensorineural hearing loss; the ages of onset were between 9 and 30 years. Mutation screening by sanger-sequencing and targeted next-generation sequencing excluded the possibility of pathogenic mutations within known deafness gene. CONCLUSIONS: A Chinese family with late-onset progressive non-syndromic sensorineural hearing loss was investigated clinically and genetically. By candidate gene approach and targeted next-generation sequencing, this family was preliminary proved to be caused by unknown deafness gene.

22 Article Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants. 2014

Shearer, A Eliot / Eppsteiner, Robert W / Booth, Kevin T / Ephraim, Sean S / Gurrola, José / Simpson, Allen / Black-Ziegelbein, E Ann / Joshi, Swati / Ravi, Harini / Giuffre, Angelica C / Happe, Scott / Hildebrand, Michael S / Azaiez, Hela / Bayazit, Yildirim A / Erdal, Mehmet Emin / Lopez-Escamez, Jose A / Gazquez, Irene / Tamayo, Marta L / Gelvez, Nancy Y / Leal, Greizy Lopez / Jalas, Chaim / Ekstein, Josef / Yang, Tao / Usami, Shin-ichi / Kahrizi, Kimia / Bazazzadegan, Niloofar / Najmabadi, Hossein / Scheetz, Todd E / Braun, Terry A / Casavant, Thomas L / LeProust, Emily M / Smith, Richard J H. ·Molecular Otolaryngology & Renal Research Labs, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. · Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA. · Agilent Technologies, Cedar Creek, TX 78612, USA. · Epilepsy Research Centre, Department of Medicine, University of Melbourne, Heidelberg, VIC 3084, Australia. · Department of Otolaryngology, Faculty of Medicine, Medipol University, Istanbul 34083, Turkey. · Department of Medical Biology and Genetics, University of Mersin, Mersin 33160, Turkey. · Otology and Neurotology Group CTS495, Center for Genomic and Oncological Research (GENyO), Granada 18012, Spain. · Instituto de Genética Humana, Pontificia Universidad Javeriana, Bogotá 11001000, Colombia. · Bonei Olam, Center for Rare Jewish Genetic Disorders, Brooklyn, NY 11204, USA. · Dor Yeshorim, The Committee for Prevention of Jewish Genetic Diseases, Brooklyn, NY 11211, USA. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, and the Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai 20025, China. · Department of Otorhinolaryngology, School of Medicine, Shinshu University, Matsumoto, Nagano 390-8621, Japan. · Genetics Research Centre, University of Social Welfare and Rehabilitation Sciences, Tehran 1985713834, Iran. · Department of Biomedical Engineering, University of Iowa, Iowa City, IA 52242, USA; Center for Bioinformatics and Computational Biology, University of Iowa, Iowa City, IA 52242, USA; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USA. · Molecular Otolaryngology & Renal Research Labs, Department of Otolaryngology-Head and Neck Surgery, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Interdepartmental PhD Program in Genetics, University of Iowa, Iowa City, IA 52242, USA; Department of Molecular Physiology & Biophysics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA. Electronic address: richard-smith@uiowa.edu. ·Am J Hum Genet · Pubmed #25262649.

ABSTRACT: Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) > 0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.

23 Article Molecular etiology of non-dominant, non-syndromic, mild-to-moderate childhood hearing impairment in Chinese Hans. 2014

Chai, Yongchuan / Pang, Xiuhong / Chen, Dongye / Li, Lei / Chen, Ying / Sun, Lianhua / Wang, Xiaowen / Wu, Hao / Yang, Tao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. ·Am J Med Genet A · Pubmed #25251670.

ABSTRACT: Childhood hearing impairment (HI) is genetically heterogeneous. Compared with the severe-to-profound HI, the molecular etiology of mild-to-moderate HI in children has been less well characterized, especially for those not inherited in the dominant mode. In this study, we recruited 114 probands with non-dominant, non-syndromic, mild-to-moderate childhood HI. Sequencing of GJB2, SLC26A4, and MTRNR1 identified causative mutations in 30.7% (35/114), 4.4% (5/114), and 4.4% (5/114) of subjects, respectively. A majority (62.9%) of bi-allelic GJB2 mutations have non-truncating mutations in at least one allele. In 10 multiplex probands with no GJB2, SLC26A4, and MTRNR1 mutations identified, targeted next-generation sequencing (NGS) of 79 known deafness genes did not identify any additional causes. Our data showed that the molecular etiology of mild-to-moderate childhood HI is considerably different from what reported for severe-to-profound HI and far from complete for those inherited in non-dominant modes.

24 Article Mutation analysis of seven consanguineous Uyghur families with non-syndromic deafness. 2014

Wang, Zhen-tao / Chen, Ying / Chen, Dong-ye / Chai, Yong-chuan / Pang, Xiu-hong / Sun, Lian-hua / Wang, Xiao-wen / Yang, Tao / Wu, Hao. ·Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medcine, Shanghai, China. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medcine, Shanghai, China. Electronic address: yangtfxl@sina.com. · Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medcine, Shanghai, China. Electronic address: wuhao622@sina.cn. ·Int J Pediatr Otorhinolaryngol · Pubmed #25015771.

ABSTRACT: OBJECTIVE: To investigate the genetic causes of consanguineous Uyghur families with nonsyndromic deafness. METHOD: Seven consanguineous Uyghur families with nonsyndromic deafness were recruited in this study and characterized for their audiometric phenotype. Mutation analysis of common deafness genes GJB2, SLC26A4 and MT-RNR1 was performed in all families by direct sequencing. RESULT: Bi-allelic mutations in SLC26A4, including p.N392Y/p.N392Y, p.S57X/p.S57X and p.Q413R/p.L676Q, were detected in three families as the pathogenic causes for the deafness. No mutations were identified in GJB2 and MT-RNR1. CONCLUSION: Mutations in SLC26A4 was the most common causes of the Uyghur consanguineous deaf families.

25 Article A novel splice site mutation in DFNA5 causes late-onset progressive non-syndromic hearing loss in a Chinese family. 2014

Chai, Yongchuan / Chen, Dongye / Wang, Xiaowen / Wu, Hao / Yang, Tao. ·Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: wuhao622@sina.cn. · Department of Otorhinolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: yangtfxl@sina.com. ·Int J Pediatr Otorhinolaryngol · Pubmed #24933359.

ABSTRACT: OBJECTIVES: Mutations in DFNA5 may lead to autosomal dominant non-syndromic sensorineural hearing loss (NSHL). To date, only four DFNA5 mutations have been reported, all resulting in skipping of exon 8 at the mRNA level. In this study, we aim to characterize the clinical features and the genetic cause of a Chinese DFNA5 family. METHODS: Targeted next-generation sequencing of 79 known deafness genes was performed in the proband. Co-segregation between the disease phenotype and the potentially pathogenic variant was confirmed in all family members by Sanger sequencing. RESULTS: A novel heterozygous c.991-2A>G mutation in DFNA5 was identified in this family segregating with the autosomal dominant, late-onset NSHL. This mutation was located in the conventional splice site in intron 7 and was likely to result in skipping of exon 8. The severity of hearing impairment varied intrafamilially. CONCLUSION: We identified a novel c.991-2A>G mutation in DFNA5 which again may lead to exon 8 skipping at the mRNA level. Our findings supported that the DFNA5-associated NSHL results from a specific gain-of-function mechanism.

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