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Hearing Disorders: HELP
Articles by Bing Han
Based on 24 articles published since 2010
(Why 24 articles?)
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Between 2010 and 2020, Bing Han wrote the following 24 articles about Hearing Disorders.
 
+ Citations + Abstracts
1 Article Nationwide population genetic screening improves outcomes of newborn screening for hearing loss in China. 2019

Wang, Qiuju / Xiang, Jiale / Sun, Jun / Yang, Yun / Guan, Jing / Wang, Dayong / Song, Cui / Guo, Ling / Wang, Hongyang / Chen, Yaqiu / Leng, Junhong / Wang, Xiaman / Zhang, Junqing / Han, Bing / Zou, Jing / Yan, Chengbin / Zhao, Lidong / Luo, Hongyu / Han, Yuan / Yuan, Wen / Zhang, Hongyun / Wang, Wei / Wang, Jian / Yang, Huanming / Xu, Xun / Yin, Ye / Morton, Cynthia C / Zhao, Lijian / Zhu, Shida / Shen, Jun / Peng, Zhiyu. ·Department of Otolaryngology-Head and Neck Surgery, Chinese PLA Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. · BGI Genomics, BGI-Shenzhen, Shenzhen, China. · Tianjin Medical Laboratory, BGI-Tianjin, BGI-Shenzhen, Tianjin, China. · Binhai Genomics Institute, BGI-Tianjin, BGI-Shenzhen, Tianjin, China. · Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. · Children's Hospital of Chongqing Medical University, Chongqing, China. · Jining Maternal and Child Health Care Service Center, Jining, China. · Tianjin Women and Children's Health Centre, Tianjing, China. · BGI Clinical Laboratory, BGI-Shenzhen, Shenzhen, China. · MGI, BGI-Shenzhen, Shenzhen, China. · Wuhan BGI Clinical Laboratory, BGI-Shenzhen, Wuhan, China. · BGI-Beijing, BGI-Shenzhen, Beijing, China. · BGI-Shenzhen, Shenzhen, China. · James D. Watson Institute of Genome Sciences, Hangzhou, China. · China National GeneBank, BGI-Shenzhen, Shenzhen, China. · Manchester Center for Audiology and Deafness, School of Health Sciences, University of Manchester, Manchester, UK. · Broad Institute of Harvard and MIT, Cambridge, MA, USA. · BGI Clinical Laboratory, BGI-Shenzhen, Shenzhen, China. zhaolijian@bgi.com. · BGI-Shenzhen, Shenzhen, China. zhushida@genomics.cn. · China National GeneBank, BGI-Shenzhen, Shenzhen, China. zhushida@genomics.cn. · Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, Shenzhen, China. zhushida@genomics.cn. · Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. jshen5@bwh.harvard.edu. · BGI Genomics, BGI-Shenzhen, Shenzhen, China. pengzhiyu@bgi.com. ·Genet Med · Pubmed #30890784.

ABSTRACT: PURPOSE: The benefits of concurrent newborn hearing and genetic screening have not been statistically proven due to limited sample sizes and outcome data. To fill this gap, we analyzed outcomes of newborns with genetic screening results. METHODS: Newborns in China were screened for 20 hearing-loss-related genetic variants from 2012 to 2017. Genetic results were categorized as positive, at-risk, inconclusive, or negative. Hearing screening results, risk factors, and up-to-date hearing status were followed up via phone interviews. RESULTS: Following up 12,778 of 1.2 million genetically screened newborns revealed a higher rate of hearing loss by three months of age among referrals from the initial hearing screening (60% vs. 5.0%, P < 0.001) and a lower rate of lost-to-follow-up/documentation (5% vs. 22%, P < 0.001) in the positive group than in the inconclusive group. Importantly, genetic screening detected 13% more hearing-impaired infants than hearing screening alone and identified 2,638 (0.23% of total) newborns predisposed to preventable ototoxicity undetectable by hearing screening. CONCLUSION: Incorporating genetic screening improves the effectiveness of newborn hearing screening programs by elucidating etiologies, discerning high-risk subgroups for vigilant management, identifying additional children who may benefit from early intervention, and informing at-risk newborns and their maternal relatives of increased susceptibility to ototoxicity.

2 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.

3 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.

4 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.

5 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.

6 Article [The study of clinical characteristics of sudden sensorineural hearing loss patients with tinnitus]. 2015

Li, Qian / Ma, Xiaojuan / Wang, Dayong / Su, Qin / Wang, Hongyang / Lan, Lan / Han, Bing / Qi, Yue / Yin, Zifang / Wu, Ziming / Xue, Xijun / Wang, Qiuju. · ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #25966557.

ABSTRACT: OBJECTIVE: To analysis the characteristics of sudden sensorineural hearing loss (SSHL) patients with tinnitus, and explore the relationship of characteristics of tinnitus and audiology. METHOD: Patients diagnosed as SSHL with tinnitus were studied in the research. All patients' clinical features were analyzed, such as tinnitus frequency, pure tone audiometry, tinnitus, hearing loss degree, results of residual inhibition test. RESULT: Thirty cases were identified as mild degree hearing loss, 13 cases as moderate degree, 28 cases as severe degree and 34 cases as profound degree. And hearing impaired frequency of 13 cases was ascertained at low-frequency, 39 cases at middle-high-frequency, and 53 cases at full-range-frequency. The incidence of patients with low-frequency was about 41. 9% (44/105), and it was about 21. 9% (23/105) in those with middle-frequency. And it was 36. 2% (38/105) in cases of high-frequency tinnitus. The chi-square test show statistically significant differences between patients with the low-frequency, middle-frequency and high-frequency of the hearing loss (P<0. 05). In tinnitus residual inhibition test, positive rate of convergence type masking curve was about 72.0%, tinnitus separated type masking curve 20.0%, overlapping type was 57.9%, and the spacing type was 43.5%. There was a statistically significant difference among cases with different type masking curve (P<0. 05)with the spacing residual inhibition test positive rate. CONCLUSION: There are individual differences of clinical characteristics among SSHL patients with tinnitus. Tinnitus frequency is consistent with the frequency of hearing loss. Patients had the more serious the degree of hearing loss, who had more serious tinnitus grading. Cases with the converged type curve will be fit for tinnitus masking. Therefore, combining the tinnitus detection with the audiological tests, we could obtain the clinical characteristics of SSHL patients with tinnitus.

7 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.

8 Article [The study of the pure tone audiometry characteristics and curative effect in sudden hearing loss patients with hypertension]. 2014

Li, Qian / Wang, Dayong / Wang, Hongyang / Lan, Lan / Han, Bing / Qi, Yue / Guan, Jing / Yin, Zifang / Wu, Ziming / Wang, Qiuju. · ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #26248453.

ABSTRACT: OBJECTIVE: To investigate the pure tone audiometry characteristics and curative effect in sudden hearing loss patients with hypertension. METHOD: One hundred and fifty-seven inpatients (168 ears) with hypertension suffered from sudden hearing loss were included in this study. We retrospectively analyzed the audiological index of these patients by comparing the pure tone audiometry (PTA) among patients in the aspects of gender, age, affected side, duration of hypertension, with or without inducement, concomitant symptoms and other combined diseases. The hearing threshold at different frequency was also compared, as well as the curative effect among patients with diverse audiological characteristics. RESULT: Of the contemporaneous sudden hearing loss patients (874 cases), the prevalence of hypertension was 17.96%, where the male ones accounted for. 28.69% (103/359) and the female ones accounted for 19.42% (54/278) respectively with statistically significant difference between genders (P < 0.01). The prevalence of hypertension in 34-44 years old group, 45-49 years old group, 60-69 years old group and over 70 years old group was 12.69% (25/197), 22.51% (70/311), 47.62% (40/84), 48.89% (22/45) respectively, which were statistically different (P < 0.01). The number of impaired ears with audiogram configuration characterized by rise type, downslope type, flat type and completely deafness type was 18 (10.71%), 61 (36.31%), 41 (24.40%), and 48 (28.57%), respectively. The decrease of hearing threshold in PTA were increasingly severe as the increasing impaired-frequency, and the difference of the degree of hearing impairment among these three types of frequencies was statistically significant (P < 0.01). The hearing threshold means of each frequency had no significant difference among patients with various gender, age and Cardiovascular Risk Stratification (P > 0.05). The hearing threshold means of each frequency of unilateral hearing loss patients was significantly higher than that of bilateral hearing loss patients (P < 0.05). The hearing threshold means at 125 Hz, 250 Hz, 500 Hz and 1 kHz showed significant difference among patients with different duration of hypertension (P < 0.05). The total effective rate of sudden hearing loss in patients with hypertension was significantly lower than that in the sudden hearing loss patients without hypertension (19.64%, 61.57% respectively, P < 0.01). The total effective rate presented significant difference among patients with different duration of hypertension and different Cardiovascular Risk Stratification (P < 0.05). CONCLUSION: The prevalence of sudden hearing loss in hypertension patients was higher in male than in female, which rose with age and combined disease. The hearing threshold means at mid-frequency and high-frequency were higher than that at low-frequency. The total effective rate of sudden hearing loss was relatively low in patients with hypertension. The longer the duration of hypertension and the higher the Cardiovascular Risk Stratification, the lower the total effective rate. Comprehensive understanding of audiological characteristics and hypertension condition plays a crucial role in type-specific treatment of sudden hearing loss.

9 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.

10 Article Exome sequencing identifies a novel frameshift mutation of MYO6 as the cause of autosomal dominant nonsyndromic hearing loss in a Chinese family. 2014

Cheng, Jing / Zhou, Xueya / Lu, Yu / Chen, Jing / Han, Bing / Zhu, Yuhua / Liu, Liyang / Choy, Kwong-Wai / Han, Dongyi / Sham, Pak C / Zhang, Michael Q / Zhang, Xuegong / Yuan, Huijun. ·Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. · MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic and Systems Biology, TNLIST/Department of Automation, Tsinghua University, Beijing, China. · Department of Psychiatry and Centre for Genomic Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China. · Li Ka Shing Institute of Health Sciences, Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China. · MCB, Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA. ·Ann Hum Genet · Pubmed #25227905.

ABSTRACT: Autosomal dominant types of nonsyndromic hearing loss (ADNSHL) are typically postlingual in onset and progressive. High genetic heterogeneity, late onset age, and possible confounding due to nongenetic factors hinder the timely molecular diagnoses for most patients. In this study, exome sequencing was applied to investigate a large Chinese family segregating ADNSHL in which we initially failed to find strong evidence of linkage to any locus by whole-genome linkage analysis. Two affected family members were selected for sequencing. We identified two novel mutations disrupting known ADNSHL genes and shared by the sequenced samples: c.328C>A in COCH (DFNA9) resulting in a p.Q110K substitution and a deletion c. 2814_2815delAA in MYO6 (DFNA22) causing a frameshift alteration p.R939Tfs*2. The pathogenicity of novel coding variants in ADNSHL genes was carefully evaluated by analysis of co-segregation with phenotype in the pedigree and in light of established genotype-phenotype correlations. The frameshift deletion in MYO6 was confirmed as the causative variant for this pedigree, whereas the missense mutation in COCH had no clinical significance. The results allowed us to retrospectively identify the phenocopy in one patient that contributed to the negative finding in the linkage scan. Our clinical data also supported the emerging genotype-phenotype correlation for DFNA22.

11 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.

12 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.

13 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.

14 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.

15 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.

16 Article [Clinical analysis of sudden sensorineural hearing loss in patients with different ages]. 2013

Wang, Da-yong / Hou, Zhi-qiang / Liu, Yan / Gao, Yun / Li, Qian / Lan, Lan / Zhao, Fei-fan / Han, Bing / Wang, Qiu-ju. ·Department of Otorhinolaryngology Head and Neck Surgery, General Hospital of People's Liberation Army, Beijing, Chin. ·Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #24016562.

ABSTRACT: OBJECTIVE: To investigate the clinical materials of sudden sensorineural hearing loss (SSNHL) in different ages of patients, and explore their clinical characteristics and prognosis. METHODS: A retrospective review was conducted by the clinical symptoms, predisposing factors and prognosis in SSNHL patients with different ages in the past two years (from 2008 to 2010). All patients were divided into three groups according to age, including Group 1 (0-18 years old), Group 2 (19-59 years old), and Group 3 (over 60 years old). RESULTS: Part of patients (28.1%) had a clear history of virus infection in Group 1. Some patients (18.7%) had obvious history of emotional fluctuations or fatigue before the onset of SSNHL. Three groups of patients with "aural fullness" symptom accounted for 3.1%, 41.3% and 29.4% respectively. The proportions of patients with profound hearing loss in three groups were 62.5%, 40.0% and 33.3% respectively. Most patients improved hearing level during systemic internal medicine treatment. However, many patients (68.8%) in Group 1 showed poor therapeutic effect. CONCLUSIONS: SSNHL in different age stages has different clinical features. We can improve the personalized treatment program to this disease through the classification and grading treatment.

17 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.

18 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.

19 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.

20 Article [Characteristics of audiology and clinical genetics of a Chinese family with the DFNA5 genetic hearing loss]. 2011

Jin, Zhanguo / Cheng, Jing / Han, Bing / Li, Hongbo / Lu, Yu / Li, Zhengyue / Han, Dongyi. ·Department of Otorhinolaryngology-Head and Neck Surgery, Institute of Otorhinolaryngology, PLA General Hospital, Beijing, 100853, China. ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #21805831.

ABSTRACT: OBJECTIVE: To analysis the characteristics of audiology and clinical genetics of a Chinese family with the DFNA5 genetic hearing loss in detail. METHOD: A detailed family history and clinical data were collected. The Chinese pedigree is an autosomal-dominant inherited hearing loss. The data of audiological examination about genetic characteristics was analysed. The relationship between the hearing-impaired of this family and age was contrasted. RESULT: This Chinese family spanned five generations and comprised 42 members. The mode of inheritance of the families should be autosomal dominant according to the pedigree. Pure-tone audiograms showed a so-called Z shape curve. The hearing loss is sensorineural, progressive and beginning at the high frequencies. The audiograms were fairly symmetric. Whole frequencies became involved with increasing age. CONCLUSION: The Chinese family with the DFNA5 mutation was an autosomal dominant pedigree. In this family, non-syndromic symmetric hearing impairment was severest at the high frequencies early, and gradually accumulated all frequencies of hearing. A mutation in DFNA5 leads to a type of hearing loss that closely resembles the frequently observed age-related hearing impairment. It should take into account DFNA5 mutation which the audiogram of a genetic hearing impaired has the same feature.

21 Article [Detection of trisomy 21 by quantitative fluorescent PCR in clinical samples undergoing prenatal diagnosis for hereditary hearing loss]. 2011

Lu, Yan-ping / Cheng, Jing / Han, Bing / Wang, Long-xia / Dai, Pu / Yuan, Hui-jun / Li, Ya-li. ·Department of Obstetrics and Gynecology, Chinese People's Liberation Army General Hospital, Beijing 100853, China. ·Zhonghua Fu Chan Ke Za Zhi · Pubmed #21781583.

ABSTRACT: OBJECTIVE: To establish the genetic test technique of trisomy 21 concurrently conducts with prenatal diagnosis for hereditary hearing loss. METHODS: Fifty-four pregnant women who underwent prenatal diagnosis for hearing loss of their fetuses in Chinese People's Liberation Army General Hospital from March 2009 to May 2010 were enrolled in this study. All probands from the deaf families have confirmed the causative mutation for hearing loss in Genetic Testing Center in Chinese People's Liberation Army General Hospital. The mean age of 54 pregnant women is 31 years at pregnancy of 18 - 26 weeks, 5 cases > pregnancy of 23 weeks, 9 cases ≥ 35 years. All subjects did not conduct the serologic tests for trisomy 21 before. Fifteen to twenty ml amniotic fluid was drawn from 49 cases at pregnancy of 18 - 23 weeks and 5 cases > pregnancy of 23 weeks. One to two ml umbilical blood was drawn from 5 cases > pregnancy of 23 weeks. For 9 cases ≥ 35 years, amniotic fluid cell culture and karyotyping analysis were conducted concurrently. A multiple quantitative fluorescent (QF) PCR and six microsatellite markers were applied to diagnosis trisomy 21. The samples with peaks of 1:1:1 or 2:1 at two microsatellite markers can be diagnosed as trisomy 21. RESULTS: (1) Fifty-four fetuses were successfully conducted prenatal genetic diagnosis for hearing loss (included GJB2 and SLC26A4). Ten fetuses copied the exactly same genotypes as the probands. The other 44 cases fetuses did not copy the same genotypes as the probands and won't develop hearing loss. The hearing test showed normal hearing for the neonates. (2) All the 54 fetuses were excluded of trisomy 21 by QF-PCR and were verified after birth. Five fetuses with advanced maternal age were performed karyotyping analysis and showed normal. The diagnostic results of QF-PCR can be obtained in 1-3 days without misdiagnosed. CONCLUSIONS: QF-PCR is an efficient, rapid and accurate technique for detection of trisomy 21 without increasing sample amount. It can be used for fetuses who were undertaken hearing loss gene test or other prenatal gene test.

22 Article Functional mutation of SMAC/DIABLO, encoding a mitochondrial proapoptotic protein, causes human progressive hearing loss DFNA64. 2011

Cheng, Jing / Zhu, Yuhua / He, Sudan / Lu, Yanping / Chen, Jing / Han, Bing / Petrillo, Marco / Wrzeszczynski, Kazimierz O / Yang, Shiming / Dai, Pu / Zhai, Suoqiang / Han, Dongyi / Zhang, Michael Q / Li, Wei / Liu, Xuezhong / Li, Huawei / Chen, Zheng-Yi / Yuan, Huijun. ·Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·Am J Hum Genet · Pubmed #21722859.

ABSTRACT: SMAC/DIABLO is a mitochondrial proapoptotic protein that is released from mitochondria during apoptosis and counters the inhibitory activities of inhibitor of apoptosis proteins, IAPs. By linkage analysis and candidate screening, we identified a heterozygous SMAC/DIABLO mutation, c.377C>T (p.Ser126Leu, refers to p.Ser71Leu in the mature protein) in a six-generation Chinese kindred characterized by dominant progressive nonsyndromic hearing loss, designated as DFNA64. SMAC/DIABLO is highly expressed in human embryonic ears and is enriched in the developing mouse inner-ear hair cells, suggesting it has a role in the development and homeostasis of hair cells. We used a functional study to demonstrate that the SMAC/DIABLO(S71L) mutant, while retaining the proapoptotic function, triggers significant degradation of both wild-type and mutant SMAC/DIABLO and renders host mitochondria susceptible to calcium-induced loss of the membrane potential. Our work identifies DFNA64 as the human genetic disorder associated with SMAC/DIABLO malfunction and suggests that mutant SMAC/DIABLO(S71L) might cause mitochondrial dysfunction.

23 Article [Sequence analysis of GJB3 in Chinese deafness population who carry one heterozygous GJB2 pathogenic mutation]. 2010

Yuan, Yong-yi / Huang, De-liang / Yu, Fei / Han, Bing / Wang, Guo-jian / Han, Dong-yi / Dai, Pu. ·Department of Otorhinolaryngology Head and Neck Surgery, General Hospital of Chinese People's Liberation Army, Beijing 100853, China. ·Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #20627047.

ABSTRACT: OBJECTIVE: To investigate whether GJB3 and GJB2 interaction to produce a deafness phenotype in a digenic mode of inheritance in Chinese deafness population. METHODS: A series of 108 patients with severe or profound hearing loss carrying one heterozygous GJB2 pathogenic mutation were sequenced for GJB3 coding region, which compared with the data of control group. RESULTS: Three GJB3 missense variants including V84I, A194T and N166S, and four GJB3 nonsense mutation were detected. N166S and A194T were considered as pathogenic which cause nonsyndromic autosomal recessive hearing loss and V84I was considered as polymorphisms in Chinese population. The two patients who carried N166S and A194T respectively in one allele also carried GJB2 235delC mutation in other allele, while the other patient who carried A194T in one allele also carried GJB2 299_300delAT mutation in other allele. CONCLUSIONS: GJB3 and GJB2 might interact to produce deafness in a digenic mode of inheritance, but the point need to be proved in further study.

24 Minor Identification of four SLC19A2 mutations in four Chinese thiamine responsive megaloblastic anemia patients without diabetes. 2014

Liu, Gang / Yang, Fan / Han, Bing / Liu, Junxiu / Nie, Guangjun. ·CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing 100190, China. Electronic address: liug268@126.com. · The First Affiliated Hospital of Jilin University, Changchun 130021, China. · Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China. · Department of Otorhinolaryngology, Peking University Third Hospital, Beijing 100191, China. Electronic address: liujunxiusanyuan@sina.com. · CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, No. 11 Zhongguancun Beiyitiao, Beijing 100190, China. Electronic address: niegj@nanoctr.cn. ·Blood Cells Mol Dis · Pubmed #24355766.

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