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Hearing Disorders: HELP
Articles by Liang Zong
Based on 28 articles published since 2009
(Why 28 articles?)
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Between 2009 and 2019, Liang Zong wrote the following 28 articles about Hearing Disorders.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review Understanding auditory neuropathy spectrum disorder: a systematic review in transgenic mouse models. 2016

Wang, Li / Guan, Jing / Wang, Hongyang / Lan, Lan / Zhang, Qiujing / Zong, Liang / Du, Wan / Xiong, Wenping / Li, Fengjiao / Wu, Kaiwen / Wang, Dayong / Wang, Qiuju. ·Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China. · Medical College, Nankai University, Tianjin, 300071, China. · Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, 100853, China. wqcr301@sina.com. ·Sci China Life Sci · Pubmed #26783139.

ABSTRACT: Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mechanism underlying this disorder is not clear. We therefore performed a systematic review of genetic mouse models with different gene mutations to provide a valuable tool for better understanding of the process and the possible molecular mechanisms. Of the 18 articles retrieved, nine met the required criteria. All biochemical, histological, and electrophysiological results were recorded for each of the mouse models, as was the transgenic technology. This review provides a summary of different mouse models that may play an important role in the diagnosis and management of auditory neuropathy spectrum disorder in the future.

2 Article Knockout of Pannexin-1 Induces Hearing Loss. 2018

Chen, Jin / Liang, Chun / Zong, Liang / Zhu, Yan / Zhao, Hong-Bo. ·Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. catkin19832002@163.com. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. chunliang13@yeah.net. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. cell-099@163.com. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. yan.zhu@uky.edu. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. hzhao2@uky.edu. ·Int J Mol Sci · Pubmed #29710868.

ABSTRACT: Mutations of gap junction connexin genes induce a high incidence of nonsyndromic hearing loss. Pannexin genes also encode gap junctional proteins in vertebrates. Recent studies demonstrated that Pannexin-1 (Panx1) deficiency in mice and mutation in humans are also associated with hearing loss. So far, several Panx1 knockout (KO) mouse lines were established. In general, these Panx1 KO mouse lines demonstrate consistent phenotypes in most aspects, including hearing loss. However, a recent study reported that a Panx1 KO mouse line, which was created by Genentech Inc., had no hearing loss as measured by the auditory brainstem response (ABR) threshold at low-frequency range (<24 kHz). Here, we used multiple auditory function tests and re-examined hearing function in the Genentech Panx1 (Gen-Panx1) KO mouse. We found that ABR thresholds in the Gen-Panx1 KO mouse were significantly increased, in particular, in the high-frequency region. Moreover, consistent with the increase in ABR threshold, distortion product otoacoustic emission (DPOAE) and cochlear microphonics (CM), which reflect active cochlear amplification and auditory receptor current, respectively, were significantly reduced. These data demonstrated that the Gen-Panx1 KO mouse has hearing loss and further confirmed that Panx1 deficiency can cause deafness.

3 Article Identification of a MYO7A mutation in a large Chinese DFNA11 family and genotype-phenotype review for DFNA11. 2018

Li, Lina / Yuan, Hu / Wang, Hongyang / Guan, Jing / Lan, Lan / Wang, Dayong / Zong, Liang / Liu, Qiong / Han, Bing / Huang, Deliang / Wang, Qiuju. ·a Department of Otolaryngology-Head and Neck Surgery , Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital , Beijing , China. · b Department of Otolaryngology , The 309th Hospital of Chinese People's Liberation Army , Beijing , China. ·Acta Otolaryngol · Pubmed #29400105.

ABSTRACT: BACKGROUND: The molecular and genetic research showed the association between DFNA11 and mutations in MYO7A. This research aimed to identify a MYO7A mutation in a family with nonsyndromic autosomal dominant hearing loss. METHODS: We have ascertained one large multigenerational Chinese family (Z029) with autosomal dominant late-onset progressive non-syndromic sensorineural hearing loss. Genome-wide linkage analysis of the family mapped the disease locus to the DFNA11 interval, where the MYO7A was considered as a candidate gene. Sequencing of the PCR products was carried out for each sample. One hundred and fifty one control subjects with normal hearing functions were also evaluated. RESULTS: The pathogenic mutation (c.2011G>A) was identified in the family. This mutation co-segregated with hearing loss in this family. No mutation of MYO7A gene was found in the 151 controls. CONCLUSIONS: The missense mutation of MYO7A is identified in the family displaying the pedigree consistent with DFNA11. We not only examined the clinical and genetic characteristics of the family, but also provided a basis for genetic counseling. We also summarized and analyzed the phenotypes and genotypes of all DFNA11 families, four of nine are Chinese families, suggesting that MYO7A mutations are not rare. Therefore, we should pay more attention to Chinese patients.

4 Article A deafness mechanism of digenic Cx26 (GJB2) and Cx30 (GJB6) mutations: Reduction of endocochlear potential by impairment of heterogeneous gap junctional function in the cochlear lateral wall. 2017

Mei, Ling / Chen, Jin / Zong, Liang / Zhu, Yan / Liang, Chun / Jones, Raleigh O / Zhao, Hong-Bo. ·Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA; Department of Otolaryngology, Xinhua Hospital, Shanghai Jiao Tong University Medical School, Shanghai 200092, PR China. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA; Department of Otolaryngology, Tongji Hospital, Huazhong University of Science & Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA; Department of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, PR China. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. · Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA. Electronic address: hzhao2@uky.edu. ·Neurobiol Dis · Pubmed #28823936.

ABSTRACT: Digenic Connexin26 (Cx26, GJB2) and Cx30 (GJB6) heterozygous mutations are the second most frequent cause of recessive deafness in humans. However, the underlying deafness mechanism remains unclear. In this study, we created different double Cx26 and Cx30 heterozygous (Cx26

5 Article Progressive age-dependence and frequency difference in the effect of gap junctions on active cochlear amplification and hearing. 2017

Zong, Liang / Chen, Jin / Zhu, Yan / Zhao, Hong-Bo. ·Dept. of Otolaryngology, University of Kentucky Medical School, Lexington, KY 40536, United States; Department of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, PR China. · Dept. of Otolaryngology, University of Kentucky Medical School, Lexington, KY 40536, United States; Department of Otolaryngology, Tongji Hospital, Huazhong University of Science & Technology, 1095 Jiefang Avenue, Wuhan 430030, PR China. · Dept. of Otolaryngology, University of Kentucky Medical School, Lexington, KY 40536, United States. · Dept. of Otolaryngology, University of Kentucky Medical School, Lexington, KY 40536, United States. Electronic address: hzhao2@uky.edu. ·Biochem Biophys Res Commun · Pubmed #28552523.

ABSTRACT: Mutations of Connexin 26 (Cx26, GJB2), which is a predominant gap junction isoform in the cochlea, can induce high incidence of nonsyndromic hearing loss. We previously found that targeted-deletion of Cx26 in supporting Deiters cells and outer pillar cells in the cochlea can influence outer hair cell (OHC) electromotility and reduce active cochlear amplification leading to hearing loss, even though there are no gap junction connexin expressions in the auditory sensory hair cells. Here, we further report that hearing loss and the reduction of active amplification in the Cx26 targeted-deletion mice are progressive and different at high and low frequency regions, first occurring in the high frequency region and then progressively extending to the middle and low frequency regions with mouse age increased. The speed of hearing loss extending was fast in the basal high frequency region and slow in the apical low frequency region, showing a logarithmic function with mouse age. Before postnatal day 25, there were no significant hearing loss and the reduction of active cochlear amplification in the low frequency region. Hearing loss and the reduction of active cochlear amplification also had frequency difference, severe and large in the high frequency regions. These new data indicate that the effect of gap junction on active cochlear amplification is progressive, but, consistent with our previous report, exists in both high and low frequency regions in adulthood. These new data also suggest that cochlear gap junctions may have an important role in age-related hearing loss.

6 Article A 2017

Du, Wan / Han, Ming-Kun / Wang, Da-Yong / Han, Bing / Zong, Liang / Lan, Lan / Yang, Ju / Shen, Qi / Xie, Lin-Yi / Yu, Lan / Guan, Jing / Wang, Qiu-Ju. ·Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China. ·Chin Med J (Engl) · Pubmed #28051029.

ABSTRACT: BACKGROUND: The molecular genetic research showed the association between X-linked hearing loss and mutations in POU3F4. This research aimed to identify a POU3F4 mutation in a nonsyndromic X-linked recessive hearing loss family. METHODS: A series of clinical evaluations including medical history, otologic examinations, family history, audiologic testing, and a high-resolution computed tomography scan were performed for each patient. Bidirectional sequencing was carried out for all polymerase chain reaction products of the samples. Moreover, 834 controls with normal hearing were also tested. RESULTS: The pedigree showed X-linkage recessive inheritance pattern, and pathogenic mutation (c.499C>T) was identified in the proband and his family member, which led to a premature termination prior to the entire POU domains. This mutation co-segregated with hearing loss in this family. No mutation of POU3F4 gene was found in 834 controls. CONCLUSIONS: A nonsense mutation is identified in a family displaying the pedigree consistent with X-linked recessive pattern in POU3F4 gene. In addition, we may provide molecular diagnosis and genetic counseling for this family.

7 Article SIX2 haploinsufficiency causes conductive hearing loss with ptosis in humans. 2016

Guan, Jing / Wang, Dayong / Cao, Wenjian / Zhao, Yali / Du, Renqian / Yuan, Hu / Liu, Qiong / Lan, Lan / Zong, Liang / Yang, Ju / Yin, Zifang / Han, Bing / Zhang, Feng / Wang, Qiuju. ·Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. · State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China. ·J Hum Genet · Pubmed #27383657.

ABSTRACT: The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environmental causes. However, the genetic basis for the risk of congenital ossicle malformation is poorly understood. We show here nine affected individuals in a Chinese pedigree who had bilateral conductive hearing loss with ptosis. We performed whole-genome sequencing and array comparative genomic hybridization (CGH) analysis on DNA samples from the Chinese pedigree. We confirmed the presence of a novel 60 kb heterozygous deletion in size, encompassing SIX2 in our family. Mutation screening in 169 sporadic cases with external ear and middle ear malformations identified no pathogenic variant or polymorphism. We suggest SIX2 haploinsufficiency as a potential congenital factor could be attributed to developmental malformation of the middle ear ossicles and upper eyelid. To the best of our knowledge, this is the first report to provide a description of copy number variation in the SIX2 gene resulting in syndromic conductive hearing loss.

8 Article Temperature sensitive auditory neuropathy. 2016

Zhang, Qiujing / Lan, Lan / Shi, Wei / Yu, Lan / Xie, Lin-Yi / Xiong, Fen / Zhao, Cui / Li, Na / Yin, Zifang / Zong, Liang / Guan, Jing / Wang, Dayong / Sun, Wei / Wang, Qiuju. ·Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: zqj99@163.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: ll-301@263.net. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: sw0215@sohu.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: anna_lan@126.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: xielinyi1234@126.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: 870505713@qq.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: zhaocui619@126.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: lna301@126.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: Yinbug@163.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: cell-099@163.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: ggy3u@126.com. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: wangdy301@126.com. · Department of Communicative Disorders & Sciences, Center for Hearing and Deafness, University at Buffalo, The State University of New York, Buffalo, NY 14215, USA. Electronic address: weisun@buffalo.edu. · Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. Electronic address: wqcr@263.net. ·Hear Res · Pubmed #26778470.

ABSTRACT: Temperature sensitive auditory neuropathy is a very rare and puzzling disorder. In the present study, we reported three unrelated 2 to 6 year-old children who were diagnosed as auditory neuropathy patients who complained of severe hearing loss when they had fever. Their hearing thresholds varied from the morning to the afternoon. Two of these patients' hearing improved with age, and one patient received positive results from cochlear implant. Genetic analysis revealed that these three patients had otoferlin (OTOF) homozygous or compound heterozygous mutations with the genotypes c.2975_2978delAG/c.4819C>T, c.4819C>T/c.4819C>T, or c.2382_2383delC/c.1621G>A, respectively. Our study suggests that these gene mutations may be the cause of temperature sensitive auditory neuropathy. The long term follow up results suggest that the hearing loss in this type of auditory neuropathy may recover with age.

9 Article Connexin26 gap junction mediates miRNA intercellular genetic communication in the cochlea and is required for inner ear development. 2015

Zhu, Yan / Zong, Liang / Mei, Ling / Zhao, Hong-Bo. ·Department of Otolaryngology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536. ·Sci Rep · Pubmed #26490746.

ABSTRACT: Organ development requires well-established intercellular communication to coordinate cell proliferations and differentiations. MicroRNAs (miRNAs) are small, non-coding RNAs that can broadly regulate gene expression and play a critical role in the organ development. In this study, we found that miRNAs could pass through gap junctions between native cochlear supporting cells to play a role in the cochlear development. Connexin26 (Cx26) and Cx30 are predominant isoforms and co-express in the cochlea. Cx26 deficiency but not Cx30 deficiency can cause cochlear developmental disorders. We found that associated with Cx26 deletion induced the cochlear developmental disorders, deletion of Cx26 but not Cx30 disrupted miRNA intercellular transfer in the cochlea, although inner ear gap junctions still retained permeability after deletion of Cx26. Moreover, we found that deletion of Cx26 but not Cx30 reduced miR-96 expression in the cochlea during postnatal development. The reduction is associated with the cochlear tunnel developmental disorder in Cx26 knockout (KO) mice. These data reveal that Cx26-mediated intercellular communication is required for cochlear development and that deficiency of Cx26 can impair miRNA-mediated intercellular genetic communication in the cochlea, which may lead to cochlear developmental disorders and eventually congenital deafness as previously reported.

10 Article Reproductive management through integration of PGD and MPS-based noninvasive prenatal screening/diagnosis for a family with GJB2-associated hearing impairment. 2015

Xiong, WenPing / Wang, DaYong / Gao, Yuan / Gao, Ya / Wang, HongYang / Guan, Jing / Lan, Lan / Yan, JunHao / Zong, Liang / Yuan, Yuan / Dong, Wei / Huang, SeXin / Wu, KeLiang / Wang, YaoShen / Wang, ZhiLi / Peng, HongMei / Lu, YanPing / Xie, LinYi / Zhao, Cui / Wang, Li / Zhang, QiuJing / Gao, Yun / Li, Na / Yang, Ju / Yin, ZiFang / Han, Bing / Wang, Wei / Chen, Zi-Jiang / Wang, QiuJu. ·Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China. · Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. · National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China. · BGI-Shenzhen, Shenzhen, 518083, China. · Department of Ultrasonography, Chinese PLA General Hospital, Beijing, 100853, China. · Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Beijing, 100853, China. · Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, China. chenzijiang@hotmail.com. · National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, China. chenzijiang@hotmail.com. · The Key laboratory for Reproductive Endocrinology of Ministry of Education, Jinan, 250021, China. chenzijiang@hotmail.com. · Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China. wqcr301@sina.com. ·Sci China Life Sci · Pubmed #26432548.

ABSTRACT: A couple with a proband child of GJB2 (encoding the gap junction protein connexin 26)-associated hearing impairment and a previous pregnancy miscarriage sought for a reproductive solution to bear a healthy child. Our study aimed to develop a customized preconception-to-neonate care trajectory to fulfill this clinical demand by integrating preimplantation genetic diagnosis (PGD), noninvasive prenatal testing (NIPT), and noninvasive prenatal diagnosis (NIPD) into the strategy. Auditory and genetic diagnosis of the proband child was carried out to identify the disease causative mutations. The couple then received in-vitro-fertilization treatment, and eight embryos were obtained for day 5 biopsy. PGD was performed by short-tandem-repeat linkage analysis and Sanger sequencing of GJB2 gene. Transfer of a GJB2c.235delC heterozygous embryo resulted in a singleton pregnancy. At the 13th week of gestation, genomic DNA (gDNA) from the trio family and cell-free DNA (cfDNA) from maternal plasma were obtained for assessment of fetal chromosomal aneuploidy and GJB2 mutations. NIPT and NIPD showed the absence of chromosomal aneuploidy and GJB2-associated disease in the fetus, which was later confirmed by invasive procedures and postnatal genetic/auditory diagnosis. This strategy successfully prevented the transmission of hearing impairment in the newborn, thus providing a valuable experience in reproductive management of similar cases and potentially other monogenic disorders.

11 Article Mutations in apoptosis-inducing factor cause X-linked recessive auditory neuropathy spectrum disorder. 2015

Zong, Liang / Guan, Jing / Ealy, Megan / Zhang, Qiujing / Wang, Dayong / Wang, Hongyang / Zhao, Yali / Shen, Zhirong / Campbell, Colleen A / Wang, Fengchao / Yang, Ju / Sun, Wei / Lan, Lan / Ding, Dalian / Xie, Linyi / Qi, Yue / Lou, Xin / Huang, Xusheng / Shi, Qiang / Chang, Suhua / Xiong, Wenping / Yin, Zifang / Yu, Ning / Zhao, Hui / Wang, Jun / Wang, Jing / Salvi, Richard J / Petit, Christine / Smith, Richard J H / Wang, Qiuju. ·Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology, PLA General Hospital, Beijing, China. · Molecular Otolaryngology and Renal Research Laboratories and the Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA Department of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, California, USA. · Department of Otolaryngology-Head and Neck Surgery, Institute of Otolaryngology, PLA General Hospital, Beijing, China Beijing Institute of Otorhinolaryngology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. · National Institute of Biological Sciences, Beijing, China. · Molecular Otolaryngology and Renal Research Laboratories and the Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, Iowa, USA. · Department of Communicative Disorders & Sciences, Center for Hearing and Deafness, University at Buffalo, Buffalo, New York, USA. · Department of Radiology, PLA General Hospital, Beijing, China. · Department of Neurology, PLA General Hospital, Beijing, China. · Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. · BGI-Shenzhen, Shenzhen, China. · Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Collège de France, Paris, France. ·J Med Genet · Pubmed #25986071.

ABSTRACT: BACKGROUND: Auditory neuropathy spectrum disorder (ANSD) is a form of hearing loss in which auditory signal transmission from the inner ear to the auditory nerve and brain stem is distorted, giving rise to speech perception difficulties beyond that expected for the observed degree of hearing loss. For many cases of ANSD, the underlying molecular pathology and the site of lesion remain unclear. The X-linked form of the condition, AUNX1, has been mapped to Xq23-q27.3, although the causative gene has yet to be identified. METHODS: We performed whole-exome sequencing on DNA samples from the AUNX1 family and another small phenotypically similar but unrelated ANSD family. RESULTS: We identified two missense mutations in AIFM1 in these families: c.1352G>A (p.R451Q) in the AUNX1 family and c.1030C>T (p.L344F) in the second ANSD family. Mutation screening in a large cohort of 3 additional unrelated families and 93 sporadic cases with ANSD identified 9 more missense mutations in AIFM1. Bioinformatics analysis and expression studies support this gene as being causative of ANSD. CONCLUSIONS: Variants in AIFM1 gene are a common cause of familial and sporadic ANSD and provide insight into the expanded spectrum of AIFM1-associated diseases. The finding of cochlear nerve hypoplasia in some patients was AIFM1-related ANSD implies that MRI may be of value in localising the site of lesion and suggests that cochlea implantation in these patients may have limited success.

12 Article Identification of a novel mutation of PJVK in the Chinese non-syndromic hearing loss population with low prevalence of the PJVK mutations. 2015

Zhang, Qiu-Jing / Lan, Lan / Li, Na / Qi, Yue / Zong, Liang / Shi, Wei / Yu, Lan / Wang, Hui / Yang, Ju / Xie, Lin-Yi / Zhao, Feifan / Wang, Da-Yong / Han, Bing / Wang, Qiu-Ju. ·Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital , Beijing , China. ·Acta Otolaryngol · Pubmed #25631766.

ABSTRACT: CONCLUSION: To our knowledge, this is the first report of PJVK gene mutation in a Chinese non-syndromic sensorineural hearing loss (NSHL) family. Our data indicate that the PJVK gene contributes to hearing impairment in the Chinese population, but it is not a major cause. OBJECTIVE: To investigate the contribution of PJVK mutations to NSHL in the Chinese population. METHODS: We screened for the PJVK gene in a sample of 65 autosomal recessive NSHL families without GJB2, SLC26A4, or mitochondrial 12S rRNA gene mutations. Seven pairs of PCR primers were designed to amplify all of the exons and their flanking regions of the PJVK gene. The PCR products were sequenced and analyzed for identification of mutations. RESULTS: In all, we identified one novel frameshift mutation, c.930_931del AC (p.C312W fsX19), co-segregating with the phenotype in one consanguineous family with a prevalence of 1.5% (1/65). The p.C312W fsX19 mutation was just positioned in the zinc-fingers domain, which was important to the function of pejvakin, and resulted in a stop codon after 19 additional amino acids. It was not identified in the controls and was considered as the causative mutation of family 804566 with autosomal recessive, non-syndromic, prelingual sensorineural hearing impairment.

13 Article [Analysis of characteristics of tinnitus in patients with auditory neuropathy spectrum disorder]. 2014

Wang, Hongyang / Qi, Yue / Guan, Jing / Lan, Lan / Xie, Linyi / Yu, Lan / Yin, Zifang / Zong, Liang / Wang, Dayong / Wang, Qiuju. · ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #26248443.

ABSTRACT: OBJECTIVE: To investigate the characteristics of tinnitus in patients with auditory neuropathy spec- trum disorder (ANSD). METHOD: This study recruited 14 ANSD patients with tinnitus. All the ANSD patients un- derwent detailed history taking, audiological examinations and assessments of tinnitus. This study analyzed the correlation of tinnitus status and hearing loss, and discussed the effects of sex, age, and the course of disease on tinnitus in ANSD patients. RESULT: (1) In the ANSD patients, tinnitus often occurred in 3 years after the onset of hearing loss; (2) Tinnitus was highly prevalent in ANSD patients, and the severity of tinnitus was mostly from mild to moderate; (3) There was no obvious correlation between the subjective grading of tinnitus and hearing loss de- gree, and the impact of curve patterns of hearing loss on the level of tinnitus need much more evidence-based proof; (4) Along with the course extension, the impact of tinnitus on the quality of life was much more obvious; (5) Some risk factors such as noise exposure could be the reasons of aggravating the degree of tinnitus. CONCLUSION: Tinnitus in ANSD patients has its unique clinical features. The study of Tinnitus in ANSD patients can provide clinical basis for further research in ANSD.

14 Article Comparative study of mutation spectrums of MT-RNR1 m.1555A>G, GJB2, and SLC26A4 between familial and sporadic patients with nonsyndromic sensorineural hearing loss in Chinese Han. 2014

Li, Qian / Ji, Yubin / Han, Bing / Zong, Liang / Lan, Lan / Zhao, Yali / Wang, Hongyang / Wang, Dayong / Wang, Qiuju. ·Department of Otolaryngology-Head and Neck Surgery, Chinese People's Liberation Army Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China. · Department of Otolaryngology, Secondary Artillery General Hospital of Chinese People's Liberation Army, Beijing 100088, China. · Department of Otolaryngology-Head and Neck Surgery, Chinese People's Liberation Army Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing 100853, China. Email: wangdy301@126.com. ·Chin Med J (Engl) · Pubmed #25266519.

ABSTRACT: BACKGROUND: The mutation frequencies of three common deafness genes (MT-RNR1 m.1555A>G, GJB2, and SLC26A4) among patients with nonsyndromic sensorineural hearing loss (NSHL) were different in previous studies. Inconsistent selection criteria for recruiting patients could have led to differences in estimating the frequencies of genetic mutations thus resulting in different mutation frequencies among these studies. The aim of this study was to reveal the differences in the mutation spectrums of the three common genes between familial and sporadic Chinese Han patients. METHODS: Totally, 301 familial probands and 703 sporadic patients with NSHL were enrolled in this study. Three genes, MT-RNR1 m.1555A>G, GJB2, and SLC26A4, were screened for mutation in our study cohort. A χ(2) test was performed to compare the mutation frequencies between the two groups. RESULTS: The study showed that the disease-causing mutation frequencies of MT-RNR1 m.1555A>G, GJB2, and SLC26A4 were 12.29%, 14.62%, and 18.27% in familial probands and 3.56%, 18.63%, and 18.92% in sporadic patients, respectively. The mutation frequency of MT-RNR1 m.1555A>G in familial probands was significantly higher than in sporadic patients (χ(2) test, P = 0.000), while there were no significant differences in the mutation frequencies of GJB2 and SLC26A4 between the familial and sporadic groups (χ(2) test, P > 0.05). CONCLUSIONS: It is necessary to reveal the differences in gene mutation frequencies between patients of different sources or characteristics by comparative studies in order to avoid selection bias. The mutations of GJB2, SLC26A4, and MT-RNR1 m.1555A>G are the most important etiological factors in Chinese Han patients, among which SLC26A4 might be the most frequent.

15 Article Targeted high-throughput sequencing identifies pathogenic mutations in KCNQ4 in two large Chinese families with autosomal dominant hearing loss. 2014

Wang, Hongyang / Zhao, Yali / Yi, Yuting / Gao, Yun / Liu, Qiong / Wang, Dayong / Li, Qian / Lan, Lan / Li, Na / Guan, Jing / Yin, Zifang / Han, Bing / Zhao, Feifan / Zong, Liang / Xiong, Wenping / Yu, Lan / Song, Lijie / Yi, Xin / Yang, Ling / Petit, Christine / Wang, Qiuju. ·Institute of Otolaryngology, Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing, China. · BGI-Tianjin, Tianjin, China. · Unité de Génétique et Physiologie de l'Audition, Institut Pasteur, Paris, France; UMRS 1120, Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France; Université Pierre et Marie Curie (Paris VI), Paris, France; Collège de France, Paris, France. ·PLoS One · Pubmed #25116015.

ABSTRACT: Autosomal dominant non-syndromic hearing loss (ADNSHL) is highly heterogeneous, among them, KCNQ4 is one of the most frequent disease-causing genes. More than twenty KCNQ4 mutations have been reported, but none of them were detected in Chinese mainland families. In this study, we identified a novel KCNQ4 mutation in a five generation Chinese family with 84 members and a known KCNQ4 mutation in a six generation Chinese family with 66 members. Mutation screening of 30 genes for ADNSHL was performed in the probands from thirty large Chinese families with ADNSHL by targeted region capture and high-throughput sequencing. The candidate variants and the co-segregation of the phenotype were verified by polymerase chain reaction (PCR) amplification and Sanger sequencing in all ascertained family members. Then we identified a novel KCNQ4 mutation p.W275R in exon 5 and a known KCNQ4 mutation p.G285S in exon 6 in two large Chinese ADNSHL families segregating with post-lingual high frequency-involved and progressive sensorineural hearing loss. This is the first report of KCNQ4 mutation in Chinese mainland families. KCNQ4, a member of voltage-gated potassium channel family, is likely to be a common gene in Chinese patients with ADNSHL. The results also support that the combination of targeted enrichment and high-throughput sequencing is a valuable molecular diagnostic tool for autosomal dominant hereditary deafness.

16 Article A novel DFNA36 mutation in TMC1 orthologous to the Beethoven (Bth) mouse associated with autosomal dominant hearing loss in a Chinese family. 2014

Zhao, Yali / Wang, Dayong / Zong, Liang / Zhao, Feifan / Guan, Liping / Zhang, Peng / Shi, Wei / Lan, Lan / Wang, Hongyang / Li, Qian / Han, Bing / Yang, Ling / Jin, Xin / Wang, Jian / Wang, Jun / Wang, Qiuju. ·Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China; Beijing Institute of Otorhinolaryngology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. · Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. · BGI-Shenzhen, Shenzhen, China. · BGI-Tianjin, Tianjin, China. · BGI-Shenzhen, Shenzhen, China; School of Bioscience and Biotechnology, South China University of Technology, Guangzhou, China. ·PLoS One · Pubmed #24827932.

ABSTRACT: Mutations in the transmembrane channel-like gene 1 (TMC1) can cause both DFNA36 and DFNB7/11 hearing loss. More than thirty DFNB7/11 mutations have been reported, but only three DFNA36 mutations were reported previously. In this study, we found a large Chinese family with 222 family members showing post-lingual, progressive sensorineural hearing loss which were consistent with DFNA36 hearing loss. Auditory brainstem response (ABR) test of the youngest patient showed a special result with nearly normal threshold but prolonged latency, decreased amplitude, and the abnormal waveform morphology. Exome sequencing of the proband found four candidate variants in known hearing loss genes. Sanger sequencing in all family members found a novel variant c.1253T>A (p.M418K) in TMC1 at DFNA36 that co-segregated with the phenotype. This mutation in TMC1 is orthologous to the mutation found in the hearing loss mouse model named Bth ten years ago. In another 51 Chinese autosomal dominant hearing loss families, we screened the segments containing the dominant mutations of TMC1 and no functional variants were found. TMC1 is expressed in the hair cells in inner ear. Given the already known roles of TMC1 in the mechanotransduction in the cochlea and its expression in inner ear, our results may provide an interesting perspective into its function in inner ear.

17 Article [Clinical analysis of in-patients with large vestibular aqueduct syndrome]. 2013

Wang, Dayong / Zhao, Yali / Zhao, Feifan / Zong, Liang / Han, Bing / Lan, Lan / Zhang, Qiujing / Qi, Yue / Wang, Qiuju. ·Department of Otolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China. ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #24417164.

ABSTRACT: OBJECTIVE: This study is to investigate the clinical materials of in-patients with the large vestibular aqueduct syndrome (LVAS), and explore the feature, diagnosis and treatment measures of the disease. METHOD: A retrospective review was conducted including the medical history, audiological examinations, vestibular function examinations, imaging examinations and treatment methods of 44 in patients (87 ears) suffering LVAS admitted to our hospital in the past 4 years(from 2008 to 2012). RESULT: ln the 44 in patients, there were 24 male cases and 20 female cases, and the male-female ratio was 1.2 :1. The average of the onset age was 3.39 years. Five cases (11. 36%) had related familial history. The profound hearing loss was found in 67 ears (77.01%), and the severe hearing loss was found in 20 ears (22.99%). After systemic treatment,the hearing of 38 ears improved effectively,but that of 49 ears did not improve obviously. The analysis found that patients suffering sudden hearing loss got better curative effect than those with progressive hearing loss. Patients received combined drug therapy improving arterial circulation as well as venous reflux got better therapeutic effect. There was a significant difference on effect between the patients with course of treatment more than 7 days and those less than 7 days. There was no significant correlation between therapeutic effect and other factors. CONCLUSION: In part of LVAS patients,the hearing level can be effectively improved through a standard internal medicine treatment. We can improve the personalized and standardized treatment strategy for this disease through analysis of diagnosis and treatment of in-patients with complete clinical data.

18 Article Correlation analysis of genotypes, auditory function, and vestibular size in Chinese children with enlarged vestibular aqueduct syndrome. 2013

Zhao, Fei-Fan / Lan, Lan / Wang, Da-Yong / Han, Bing / Qi, Yue / Zhao, Yali / Zong, Liang / Li, Qian / Wang, Qiu-Ju. ·Department of Otorhinolaryngology/Head and Neck Surgery, Chinese People's Liberation Army Institute of Otolaryngology, Chinese People's Liberation Army General Hospital , Beijing , China. ·Acta Otolaryngol · Pubmed #24245694.

ABSTRACT: CONCLUSION: In children with enlarged vestibular aqueduct syndrome (EVAS), their hearing was more related to genotype than VA size, and VA size was related to genotype. OBJECTIVE: To study genotypes of the SLC26A4 gene, types and levels of hearing loss, and vestibular aqueduct (VA) size in children with EVAS. METHODS: A total of 271 children with nonsyndromic sensorineural hearing loss and EVA underwent SLC26A4 gene screening. According to genotype typing, the phenotypes including pure tone average (PTA), distribution of subjects, and diameters of the external aperture and middle portion of the VA, were compared by t test or Pearson's χ(2) tests. Further, divided by the dilated level of the VA, subject distribution in different hearing loss levels was compared by Pearson's χ(2) test. RESULTS: In all, 66 types of mutations were identified and 2 were novel (c.665G >T and c.1639G >A). Biallelic genotype was found in 207 subjects, monoallelic in 56, and no mutation in 8. The hearing loss was more stable in the subjects with monoallelic mutation than in other genotype groups. An air-bone gap was more frequently found in subjects with biallelic missense mutations than in other groups. The patients with no mutation had the most slightly enlarged VA. There was no dominant correlation between hearing loss level and VA size, and between VA size and different genotypes.

19 Article Newborn hearing concurrent genetic screening for hearing impairment-a clinical practice in 58,397 neonates in Tianjin, China. 2013

Zhang, Junqing / Wang, Peng / Han, Bing / Ding, Yibing / Pan, Lei / Zou, Jing / Liu, Haisheng / Pang, Xinzhi / Liu, Enqing / Wang, Hongyue / Liu, Hongyan / Zhang, Xudong / Cheng, Xiu / Feng, Dafei / Li, Qian / Wang, Dayong / Zong, Liang / Yi, Yuting / Tian, Ning / Mu, Feng / Tian, Geng / Chen, Yaqiu / Liu, Gongshu / Zhang, Fuxia / Yi, Xin / Yang, Ling / Wang, Qiuju. ·BGI-Tianjin, Tianjin, China; Tianjin Medical Genomics Technology Engineering Center, Tianjin, China. ·Int J Pediatr Otorhinolaryngol · Pubmed #24100002.

ABSTRACT: OBJECTIVE: Newborn hearing screening (NHS) is used worldwide due to its feasibility and cost-efficiency. However, neonates with late-onset and progressive hearing impairment will be missed by NHS. Genetic factors account for an estimated 60% of congenital profound hearing loss. Our previous cohort studies were carried out in an innovative mode, i.e. hearing concurrent genetic screening, in newborns to improve the abilities or early diagnosis and intervention for the hearing defects. In this study, we performed the first clinical practice of this mode in Tianjin city. METHODS: A large cohort of 58,397 neonates, born between December 2011 and December 2012, in 44 hospitals in Tianjin, were screened for 20 hot spot hearing loss associated mutations from GJB2, GJB3, SLC26A4 and MTRNR1(12S rRNA). The data of genetic screening results was comprehensively analyzed with newborn hearing screening (NHS) results. RESULTS: We developed an accurate, high throughput genetic screening method and applied it to a total of 58,397 newborns in Tianjin. 3225 (5.52%) infants were detected to carry at least one mutation allele in GJB2, GJB3, SLC26A4 or MTRNR1. 34 (0.58‰) infants were positive for hearing loss caused by GJB2 or SLC26A4 mutations (homozygote or compound heterozygote). 54(0.93‰) infants are heterozygous of various genes. 109(1.87‰) infants had the pathological mitochondrial DNA mutation. CONCLUSION: Accurate, comprehensive hearing loss associated genetic screening can facilitate genetic counseling and provides valuable prognostic information to affected infants. This united screening mode of this study was a promising clinical practice.

20 Article [Clinical and prognostic analyses of juvenile sudden sensorineural hearing loss]. 2013

Wang, Da-yong / Hou, Zhi-qiang / Liu, Yan / Gao, Yun / Zhao, Fei-fan / Zong, Liang / Lan, Lan / Wang, Qiu-ju. ·Department of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·Zhonghua Yi Xue Za Zhi · Pubmed #24028727.

ABSTRACT: OBJECTIVE: To explore the clinical profiles of juvenile sudden sensorineural hearing loss (JSSNHL) and examine its clinical characteristics and prognosis. METHODS: A retrospective review was conducted for the clinical symptoms, audiological characteristics, hematological indices and prognosis in JSSNHL during the past 2 years (from June 2008 to November 2010). All patients were divided into 2 groups according to age, that is group childhood (A, 0-12 years old) and group adolescence (B, 13-18 years old). RESULTS: JSSNHL patients were rarely associated with "aural fullness" symptoms. Two groups of patients with "tinnitus" symptom accounted for 88.2% and 89.5%. Those with "vertigo" symptom accounted for 47.1% and 44.4% respectively. Most patients (81.6%) showed severe and profound hearing loss. The most common types of audiometric curve were flat and total deafness. Some obvious differences existed between two groups in hematological indices, such as platelet count, concentrations of electrolyte ions, mean corpuscular volume and mean corpuscular hemoglobin. Almost half of them (42.1%) improved hearing level during systemic medical treatment. The patients of two groups showed no significant difference in efficacies. And the hearing enhancement degree of patients in group B was more apparent than that of group A. CONCLUSIONS: JSSNHL has different clinical features in different age groups. And the outcomes of personalized treatment regimens may be further improved through classification and grading.

21 Article Exome sequencing and linkage analysis identified tenascin-C (TNC) as a novel causative gene in nonsyndromic hearing loss. 2013

Zhao, Yali / Zhao, Feifan / Zong, Liang / Zhang, Peng / Guan, Liping / Zhang, Jianguo / Wang, Dayong / Wang, Jing / Chai, Wei / Lan, Lan / Li, Qian / Han, Bing / Yang, Ling / Jin, Xin / Yang, Weiyan / Hu, Xiaoxiang / Wang, Xiaoning / Li, Ning / Li, Yingrui / Petit, Christine / Wang, Jun / Wang, Huanming Yang Jian / Wang, Qiuju. ·Department of Otorhinolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·PLoS One · Pubmed #23936043.

ABSTRACT: In this study, a five-generation Chinese family (family F013) with progressive autosomal dominant hearing loss was mapped to a critical region spanning 28.54 Mb on chromosome 9q31.3-q34.3 by linkage analysis, which was a novel DFNA locus, assigned as DFNA56. In this interval, there were 398 annotated genes. Then, whole exome sequencing was applied in three patients and one normal individual from this family. Six single nucleotide variants and two indels were found co-segregated with the phenotypes. Then using mass spectrum (Sequenom, Inc.) to rank the eight sites, we found only the TNC gene be co-segregated with hearing loss in 53 subjects of F013. And this missense mutation (c.5317G>A, p.V1773M ) of TNC located exactly in the critical linked interval. Further screening to the coding region of this gene in 587 subjects with nonsyndromic hearing loss (NSHL) found a second missense mutation, c.5368A>T (p. T1796S), co-segregating with phenotype in the other family. These two mutations located in the conserved region of TNC and were absent in the 387 normal hearing individuals of matched geographical ancestry. Functional effects of the two mutations were predicted using SIFT and both mutations were deleterious. All these results supported that TNC may be the causal gene for the hearing loss inherited in these families. TNC encodes tenascin-C, a member of the extracellular matrix (ECM), is present in the basilar membrane (BM), and the osseous spiral lamina of the cochlea. It plays an important role in cochlear development. The up-regulated expression of TNC gene in tissue repair and neural regeneration was seen in human and zebrafish, and in sensory receptor recovery in the vestibular organ after ototoxic injury in birds. Then the absence of normal tenascin-C was supposed to cause irreversible injuries in cochlea and caused hearing loss.

22 Article Newborn genetic screening for high risk deafness-associated mutations with a new Tetra-primer ARMS PCR kit. 2013

Han, Bing / Zong, Liang / Li, Qian / Zhang, Zhidong / Wang, Dayong / Lan, Lan / Zhang, Jingxin / Zhao, Yali / Wang, Qiuju. ·Department of Otolaryngology-Head and Neck Surgery, and Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing, China. ·Int J Pediatr Otorhinolaryngol · Pubmed #23815884.

ABSTRACT: OBJECTIVE: Previous epidemiological studies indicate that GJB2, SLC26A4 or mtDNA 12S rRNA mutations were chiefly responsible for the hearing loss in children. A cost-effective method for screening deafness-associated mutations at early age is needed. This study aimed to develop a simple kit for screening of high risk deafness-associated mutations in newborns using tetra-primer amplification refractory mutation system PCR. METHODS: The screening kit was designed to detect high risk deafness-associated mutations (GJB2 c.235delC, SLC26A4 c.919-2A>G, mtDNA 12S rRNA mt.1555A>G and mt.1494C>T). The kit was able to amplify both wild-type and mutant alleles with a control fragment. The proposed method was conducted to genotype the above four deafness gene mutations in four PCR reactions. Each mutation was genotyped by a set of four primers, two allele-specific inner primers, and two common outer primers. A mismatch at the penultimate or antepenult nucleotide of the 3' terminus was introduced in order to maximize specificity. The 16 primers were used for the amplification of genomic DNA as a template. Amplified fragments were separated by electrophoresis. We designed and validated the kit with wild and mutant type DNA samples that had been previously been confirmed by Sanger sequencing. Then 1181 newborns were enrolled, and those samples with mutations were further validated with sequencing too. RESULTS: Among 1181 newborns, 29 individuals had one or two mutant alleles, with the carrier rate being 2.46% (29/1181). For GJB2 c.235delC mutation, one case was homozygote and 12 cases were heterozygote carriers. For SLC26A4 c.919-2A>G mutation, 12 cases were heterozygotes carriers, and no homozygotes were found; for mtDNA 12S rRNA mt.1555A>G mutation, one case was identified; three cases of mtDNA 12S rRNA mt.1494C>T mutation were detected. All mutations were detected with high specificity. Mutation samples were confirmed via Sanger sequencing. No false positive was found. CONCLUSION: A user-friendly screening kit for deafness-associated mutations was successfully developed. It provided rapid, reproducible, and cost-effective detection of deafness gene mutation without special equipment. The kit allowed the detection of the four high risk deafness-associated mutations with only 4 single tube PCR reactions. In the future, the kit could be applied to large population-based epidemiological studies for newborn hearing defects screening.

23 Article Active cochlear amplification is dependent on supporting cell gap junctions. 2013

Zhu, Yan / Liang, Chun / Chen, Jin / Zong, Liang / Chen, Guang-Di / Zhao, Hong-Bo. ·Department of Otolaryngology, University of Kentucky Medical School, Lexington, Kentucky 40536, USA. ·Nat Commun · Pubmed #23653198.

ABSTRACT: Mammalian hearing relies upon active cochlear mechanics, which arises from outer hair cell electromotility and hair bundle movement, to amplify acoustic stimulations increasing hearing sensitivity and frequency selectivity. Here we describe the novel finding that gap junctions between cochlear supporting cells also have a critical role in active cochlear amplification in vivo. We find that targeted-deletion of connexin 26 in Deiters cells and outer pillar cells, which constrain outer hair cells standing on the basilar membrane, causes a leftward shift in outer hair cell electromotility towards hyperpolarization, and reduces active cochlear amplification with hearing loss. Coincident with large reduction in distortion product otoacoustic emission and severe hearing loss at high frequencies, the shift is larger in shorter outer hair cells. Our study demonstrates that active cochlear amplification in vivo is dependent on supporting cell gap junctions. These new findings also show that connexin 26 deficiency can reduce active cochlear amplification to induce hearing loss.

24 Article Cell degeneration is not a primary causer for Connexin26 (GJB2) deficiency associated hearing loss. 2012

Liang, Chun / Zhu, Yan / Zong, Liang / Lu, Guang-Jin / Zhao, Hong-Bo. ·Department of Otolaryngology, University of Kentucky Medical School, Lexington, KY 40536, USA. ·Neurosci Lett · Pubmed #22975134.

ABSTRACT: Connexin26 (Cx26, GJB2) mutations can induce congenital deafness and are responsible for ∼50% of nonsyndromic hearing loss in children. Mouse models show that Cx26 deficiency induces cochlear development disorder, hair cell loss, and spiral ganglion (SG) neuron degeneration. Hair cell loss and cell degeneration have been considered as a primary causer responsible for Cx26 deficiency associated hearing loss. In this study, by coincidental examination of cochlear postnatal development with recording of auditory brainstem response (ABR) and hair cell function, we found that occurrence of hearing loss in Cx26 knockout (KO) mice was ahead of hair cell loss and cochlear cell degeneration. ABR was absent at the whole-frequency range (8-40 kHz) after birth. However, cochlear cells including SG neurons had no significant degeneration throughout postnatal development. Severe cochlear hair cell loss and SG neuron degeneration were only visible in middle and basal turns, i.e., in middle and high frequency regions, in the adult Cx26 KO mouse cochlea. Functional tests show that hair cells in Cx26 KO mice functioned normally; outer hair cells retained electromotility. These data suggest that cell degeneration is not a primary causer of Cx26 deficiency associated hearing loss. Some mechanisms other than cell degeneration, such as cochlear development disorders, may play an essential role in this common hereditary deafness.

25 Article Unilateral auditory neuropathy spectrum disorder. 2012

Zhang, Qiu-Jing / Lan, Lan / Shi, Wei / Wang, Da-Yong / Qi, Yue / Zong, Liang / Li, Qian / Wang, Hui / Ding, Hai-Na / Li, Na / Han, Bing / Wang, Qiu-Ju. ·Department of Otolaryngology/Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·Acta Otolaryngol · Pubmed #22073929.

ABSTRACT: CONCLUSIONS: The majority of the patients with unilateral auditory neuropathy spectrum disorder (UANSD) were pediatric and mostly showed a great degree of hearing loss when diagnosed. Abnormal auditory brainstem response (ABR) and preserved otoacoustic emissions (OAEs) and/or cochlear microphonics (CM) were important features to differentiate it from common sensorineural deafness and central nerve hearing loss. OBJECTIVE: To identify the clinical characteristics of patients with UANSD. METHODS: This was a retrospective study involving 14 patients diagnosed as having UANSD between 2004 and 2010 in the Chinese PLA Hospital. RESULTS: In all, 50% of the cases were males (1:1 sex ratio) and the average age of onset was 4.1 years. Of the 14 affected ears with UANSD in these cases, 6 were left-sided, while 8 were right-sided. Of the 14 contralateral ears, 4 presented with sensorineural hearing loss, while the other 10 showed normal hearing. The degree of hearing loss in the 14 affected ears varied, including moderate in 1, moderately severe in 4, severe in 5, and profound in 4. ABRs were absent in the 14 affected ears, while the OAEs, and/or CM were present.

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