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Hearing Disorders: HELP
Articles by Jing Cheng
Based on 21 articles published since 2010
(Why 21 articles?)
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Between 2010 and 2020, Jing Cheng wrote the following 21 articles about Hearing Disorders.
 
+ Citations + Abstracts
1 Article Novel OTOF gene mutations identified using a massively parallel DNA sequencing technique in DFNB9 deafness. 2018

Wang, Yanfei / Lu, Yu / Cheng, Jing / Zhang, Lei / Han, Dongyi / Yuan, Huijun. ·a Department of Otolaryngology Head and Neck Surgery , Chinese PLA General Hospital , Beijing , China. · b Medical Genetics Center, Southwest Hospital , Army Medical University , Chongqing , China. ·Acta Otolaryngol · Pubmed #30073893.

ABSTRACT: OBJECTIVES: This study examined the causative genes in patients with early-onset hearing loss from two Chinese families. METHOD: Massively parallel sequencing, designed to screen all reported genes associated with hearing loss, was performed in a large number of Chinese individuals with hearing loss. This study enrolled patients with the same OTOF mutation and analyzed their phenotype-genotype correlations. RESULTS: Three novel OTOF mutations (NM_001287489) [c.1550T > C (p.L517P), c.5900_5902delTCA (p.I1967del), and c.4669_4677delCTGACGGTG (p.L1557-V1559del)] were found to be the cause of hearing loss in five patients. In family AH-890, the affected subject homozygous for p.L517P presented with profound hearing loss, while the affected sisters compound heterozygous for p.L517P and p.I1967del had mild-to-moderate hearing loss. The patient with hearing loss in family SD-345 was found to be compound heterozygous for p.L517P and p.L1557-V1559del. CONCLUSION: Three presumably pathogenic mutations in the OTOF gene were detected for the first time, including the first pathogenic mutation detected in the TM domain. In addition to expanding the spectrum of OTOF mutations resulting in DFNB9, our findings present the diversity of its clinical presentation and indicate that MPS is an efficient approach to identify the causative genes associated with hereditary hearing loss.

2 Article Identification of Pathogenic Genes of Nonsyndromic Hearing Loss in Uyghur Families Using Massively Parallel DNA Sequencing Technique. 2018

Chen, Yu / Lu, Yu / Kuyaxi, Pilidong / Cheng, Jing / Zhao, Juan / Zhao, Qi / Musha, Patiguli / Zhang, Hua / Yuan, Huijun. ·Department of Otorhinolaryngology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China. · Medical Genetics Center, The First Affiliated Hospital, Army Medical University, Chongqing 400038, China. · Department of Otorhinolaryngology, The First People's Hospital, Kashi Municipality, Xinjiang 844000, China. ·Dis Markers · Pubmed #29692870.

ABSTRACT: We aim to identify the mutations of deafness genes using massively parallel DNA sequencing in the 12 Uyghur families. SNPscan method was used to screen against the 124 sites in the common deafness genes in probands. Subjects with SNPscan negativity were subject to massively parallel DNA sequencing for the sequencing of 97 genes known to be responsible for hearing loss. Eight families (66.7%) showed biallelic mutations in probands, including

3 Article Screening of deafness-causing DNA variants that are common in patients of European ancestry using a microarray-based approach. 2017

Yan, Denise / Xiang, Guangxin / Chai, Xingping / Qing, Jie / Shang, Haiqiong / Zou, Bing / Mittal, Rahul / Shen, Jun / Smith, Richard J H / Fan, Yao-Shan / Blanton, Susan H / Tekin, Mustafa / Morton, Cynthia / Xing, Wanli / Cheng, Jing / Liu, Xue Zhong. ·Department of Otolaryngology, University of Miami Miller School of Medicine, Miami, Florida, United States of America. · National Engineering Research Center for Beijing Biochip Technology, Beijing, China. · Tsinghua University School of Medicine, Beijing, China. · Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. · Laboratory for Molecular Medicine, Partners Personalized Medicine, Cambridge, Massachusetts, United States of America. · Department of Otolaryngology - Head and Neck Surgery, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America. · Department of Pathology, University of Miami Miller School of Medicine, Miami, Florida, United States of America. · Dr. John T. Macdonald Department of Human Genetics and John P.Hussman Institute for Human Genetics, University of Miami Miller School of Medicine, Miami, Florida, United States of America. · Department of Obstetrics, Gynecology and Reproductive Biology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, United States of America. · Division of Evolution and Genomic Science, School of Biological Sciences, Manchester Academic Health Science Center, University of Manchester, United Kingdom. ·PLoS One · Pubmed #28273078.

ABSTRACT: The unparalleled heterogeneity in genetic causes of hearing loss along with remarkable differences in prevalence of causative variants among ethnic groups makes single gene tests technically inefficient. Although hundreds of genes have been reported to be associated with nonsyndromic hearing loss (NSHL), GJB2, GJB6, SLC26A4, and mitochondrial (mt) MT-RNR1 and MTTS are the major contributors. In order to provide a faster, more comprehensive and cost effective assay, we constructed a DNA fluidic array, CapitalBioMiamiOtoArray, for the detection of sequence variants in five genes that are common in most populations of European descent. They consist of c.35delG, p.W44C, p.L90P, c.167delT (GJB2); 309kb deletion (GJB6); p.L236P, p.T416P (SLC26A4); and m.1555A>G, m.7444G>A (mtDNA). We have validated our hearing loss array by analyzing a total of 160 DNAs samples. Our results show 100% concordance between the fluidic array biochip-based approach and the established Sanger sequencing method, thus proving its robustness and reliability at a relatively low cost.

4 Article Application of SNPscan in Genetic Screening for Common Hearing Loss Genes. 2016

Gao, Zixuan / Lu, Yu / Ke, Jia / Li, Tao / Hu, Ping / Song, Yu / Xu, Chiyu / Wang, Jie / Cheng, Jing / Zhang, Lei / Duan, Hong / Yuan, Huijun / Ma, Furong. ·Department of Otolaryngology, 3rd Hospital of Peking University, Beijing, China. · Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. · Medical Genetics Center, Southwest Hospital, Third Military Medical University, Chong-qing, China. ·PLoS One · Pubmed #27792752.

ABSTRACT: The current study reports the successful application of a fast and efficient genetic screening system for common hearing loss (HL) genes based on SNPscan genotyping technology. Genetic analysis of 115 variants in common genes related to HL, GJB2, SLC26A4 and MT-RNR, was performed on 695 subjects with non-syndromic hearing loss (NSHL) from the Northern China. The results found that 38.7% (269/695) of cases carried bi-allelic pathogenic variants in GJB2 and SLC26A4 and 0.7% (5/695) of cases carried homoplasmic MT-RNR1 variants. The variant allele frequency of GJB2, SLC26A4 and MT-RNR1 was 19.8% (275/1390), 21.9% (304/1390), and 0.86% (6/695), respectively. This approach can explain ~40% of NSHL cases and thus is a useful tool for establishing primary molecular diagnosis of NSHL in clinical genetics.

5 Article [A novel technique for simultaneous multi-gene mutation screening in 225 patients with nonsyndromic hearing loss]. 2016

Zhang, Di / Duan, Hong / Lin, Peng / Cheng, Jing / Wang, Cuicui / Ma, Yuanxu / Cheng, Yan / Zhao, Hui / Wang, Wei / Xu, Kaixu / Han, Dongyi / Yuan, Huijun. ·Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otorhinolaryngology, General Hospital of People's Liberation Army, Beijing 100853, China; Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otorhinolaryngology, Tianjin First Center Hospital, Tianjin 300192, China. · Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otorhinolaryngology, General Hospital of People's Liberation Army, Beijing 100853, China. · Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otorhinolaryngology, Tianjin First Center Hospital, Tianjin 300192, China. · Medical Genetics Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. · Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otorhinolaryngology, General Hospital of People's Liberation Army, Beijing 100853, China; Medical Genetics Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. ·Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #27033575.

ABSTRACT: OBJECTIVE: Using simultaneous multi-gene mutation screening to investigate the new method molecular epidemiological basis of 225 patients with nonsyndromic hearing loss in Tianjin, and verifying the for simultaneous multi-gene mutation screening. METHODS: Two hundred and twenty-five patients with severe non-syndromic deafness from Tianjin CDPF and Association of the Deaf were included in the study. The single nucleotide polymorphisms scan, (SNPscan) technique was used for screening the 115 spots mutations in three common deafness-related genes (GJB2, SLC26A4, mtDNA 12S rRNA) of patients with nonsyndromic hearing loss in Tianjin. We verified the results by Sanger sequencing. RESULTS: Among the 225 patients, there were 111 cases of deafness caused by mutation (49.3%). Using this method, up to 50% of the patients in our study were identified to have hereditary HL caused by mutations in the three genes. 56 patients with the GJB2 mutations were detected (24.9%), including 30 cases of homozygous mutations (13.3%), 26 patients (11.6%) of compound heterozygous mutations, and 21 cases (9.33%) of single heterozygous mutations. 50 patients with the SLC26A4 mutations were detected (22.2%), including 22 cases of homozygous mutations(9.8%), 28 patients (12.4%) of compound heterozygous mutations, and 22 cases (9.8%) of single heterozygous mutations. mtDNA 12S rRNA A1555G mutation was detected in 5 patients (2.2%). mtDNA 12S rRNA 1494C>T mutation was not detected. We verified the results by Sanger sequencing. The accuracy of the sequencing results was 100%. The SNPscan cost eight hours and 160 yuan (each sample). CONCLUSIONS: Applying SNPscan technology can be accurate, rapid and cost-effective diagnostic screening in patients with hearing loss for etiology investigation. It is expected to become an effective means of large-scale genetic testing for hereditary deafness.

6 Article A novel mutation of EYA4 in a large Chinese family with autosomal dominant middle-frequency sensorineural hearing loss by targeted exome sequencing. 2015

Sun, Yi / Zhang, Zhao / Cheng, Jing / Lu, Yu / Yang, Chang-Liang / Luo, Yan-Yun / Yang, Guang / Yang, Hui / Zhu, Li / Zhou, Jia / Yao, Hang-Qi. ·Department of Otolaryngology, Chinese PLA Wuhan General Hospital of Guangzhou Military Command, Wuhan, China. · Department of Otorhinolaryngology Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·J Hum Genet · Pubmed #25809937.

ABSTRACT: The middle-frequency sensorineural hearing loss (MFSNHL) is rare among hereditary non-syndromic hearing loss. To date, only three genes are reported to be associated with MFSNHL, including TECTA, EYA4 and COL11A2. In this report, we analyzed and explored the clinical audiological characteristics and the causative gene of a Chinese family named HG-Z087 with non-syndromic autosomal dominant inherited MFSNHL. Clinical audiological characteristics and inheritance pattern of a family were evaluated, and pedigree was drawn based on medical history investigation. Our results showed that the Chinese family was characterized by late onset, progressive, non-sydromic autosomal dominant MFSNHL. Targeted exome sequencing, conducted using DNA samples of an affected member in this family, revealed a novel heterozygous missense mutation c.1643C>G in exon 18 of EYA4, causing amino-acid (aa) substitution Arg for Thr at a conserved position aa-548. The p.T548R mutation related to hearing loss in the selected Chinese family was validated by Sanger sequencing. However, the mutation was absent in control group containing 100 DNA samples from normal Chinese families. In conclusion, we identified the pathogenic gene and found that the novel missense mutation c.1643C>G (p.T548R) in EYA4 might have caused autosomal dominant non-syndromic hearing impairment in the selected Chinese family.

7 Article KCNJ10 may not be a contributor to nonsyndromic enlargement of vestibular aqueduct (NSEVA) in Chinese subjects. 2014

Zhao, Jiandong / Yuan, Yongyi / Huang, Shasha / Huang, Bangqing / Cheng, Jing / Kang, Dongyang / Wang, Guojian / Han, Dongyi / Dai, Pu. ·Department of Otolaryngology, PLA General Hospital, Beijing, People's Republic of China. · Department of Otolaryngology, PLA General Hospital, Beijing, People's Republic of China; Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, People's Republic of China. · Department of Otolaryngology, Hainan Branch of PLA General Hospital, Sanya, People's Republic of China. ·PLoS One · Pubmed #25372295.

ABSTRACT: BACKGROUND: Nonsyndromic enlargement of vestibular aqueduct (NSEVA) is an autosomal recessive hearing loss disorder that is associated with mutations in SLC26A4. However, not all patients with NSEVA carry biallelic mutations in SLC26A4. A recent study proposed that single mutations in both SLC26A4 and KCNJ10 lead to digenic NSEVA. We examined whether KCNJ10 excert a role in the pathogenesis of NSEVA in Chinese patients. METHODS: SLC26A4 was sequenced in 1056 Chinese patients with NSEVA. KCNJ10 was screened in 131 patients who lacked mutations in either one or both alleles of SLC26A4. Additionally, KCNJ10 was screened in 840 controls, including 563 patients diagnosed with NSEVA who carried biallelic SLC26A4 mutations, 48 patients with nonsyndromic hearing loss due to inner ear malformations that did not involve enlargement of the vestibular aqueduct (EVA), 96 patients with conductive hearing loss due to various causes, and 133 normal-hearing individuals with no family history of hereditary hearing loss. RESULTS: 925 NSEVA patients were found carrying two-allele pathogenic SLC26A4 mutations. The most frequently detected KCNJ10 mutation was c.812G>A (p.R271H). Compared with the normal-hearing control subjects, the occurrence rate of c.812G>A in NSEVA patients with lacking mutations in one or both alleles of SLC26A4 had no significant difference(1.53% vs. 5.30%, χ(2) = 2.798, p = 0.172), which suggested that it is probably a nonpathogenic benign variant. KCNJ10 c.1042C>T (p.R348C), the reported EVA-related mutation, was not found in patients with NSEVA who lacked mutations in either one or both alleles of SLC26A4. Furthermore, the normal-hearing parents of patients with NSEVA having two SLC26A4 mutations carried the KCNJ10 c.1042C>T or c.812G>A mutation and a SLC26A4 pathogenic mutation. CONCLUSION: SLC26A4 is the major genetic cause in Chinese NSEVA patients, accounting for 87.59%. KCNJ10 may not be a contributor to NSEVA in Chinese population. Other genetic or environmental factors are possibly play a role in the etiology of Chinese EVA patients with zero or monoallelic SLC26A4 mutation.

8 Article Resolving the genetic heterogeneity of prelingual hearing loss within one family: Performance comparison and application of two targeted next generation sequencing approaches. 2014

Lu, Yu / Zhou, Xueya / Jin, Zhanguo / Cheng, Jing / Shen, Weidong / Ji, Fei / Liu, Liyang / Zhang, Xuegong / Zhang, Michael / Cao, Ye / Han, Dongyi / Choy, KwongWai / Yuan, Huijun. ·Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. · 1] MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic and Systems Biology, TNLIST/Department of Automation, Tsinghua University, Beijing, China [2] Department of Psychiatry, The University of Hong Kong, Hong Kong, SAR, China. · Department of Otolaryngology, Chinese PLA Air Force 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. · 1] MOE Key Laboratory of Bioinformatics, Bioinformatics Division and Center for Synthetic and Systems Biology, TNLIST/Department of Automation, Tsinghua University, Beijing, China [2] MCB, Center for Systems Biology, The University of Texas at Dallas, Richardson, TX, USA. · 1] Department of Obstetrics and Gynaecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China [2] CUHK-University of Utrecht Joint Centre for Language, Mind and Brain, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China. ·J Hum Genet · Pubmed #25231367.

ABSTRACT: Here, we report an unconventional Chinese pedigree consisting of three branches all segregating prelingual hearing loss (HL) with unclear inheritance pattern. After identifying the cause of one branch as maternally inherited aminoglycoside-induced HL, targeted next generation sequencing (NGS) was applied to identify the genetic causes for the other two branches. One affected subject from each branch was subject to targeted NGS whose genomic DNA was enriched either by whole-exome capture (Agilent SureSelect All Exon 50 Mb) or by candidate genes capture (Agilent SureSelect custom kit). By NGS analysis, we identified that patients from Branch A were compound heterozygous for p.E1006K and p.D1663V in the CDH23 (DFNB12) gene; and patients from Branch B were homozygous for IVS7-2A>G in the SLC26A4 (DFNB4) gene. Both CDH23 mutations altered conserved calcium binding sites of the extracellular cadherin domains. The co-occurrence of three different genetic causes in this family was exceedingly rare but fully compatible with the mutation spectrum of HL. Our study has also raised several technical and analytical issues when applying the NGS technique to genetic testing.

9 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.

10 Article A rapid method for simultaneous multi-gene mutation screening in children with nonsyndromic hearing loss. 2014

Du, Wan / Cheng, Jing / Ding, Hui / Jiang, Zhengwen / Guo, Yufen / Yuan, Huijun. ·Department of Otolaryngology-Head and Neck Surgery, the Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China; Department of Otolaryngology-Head and Neck Surgery, Chinese People's Liberation Army Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China. · Department of Otolaryngology-Head and Neck Surgery, Chinese People's Liberation Army Institute of Otolaryngology, Chinese People's Liberation Army General Hospital, Beijing, People's Republic of China. · Department of Urology, the Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China. · Center for Human Genetics Research, Genesky Biotechnologies Inc., Shanghai, People's Republic of China. · Department of Otolaryngology-Head and Neck Surgery, the Second Hospital of Lanzhou University, Lanzhou, Gansu, People's Republic of China. ·Genomics · Pubmed #25149764.

ABSTRACT: Hearing loss (HL) is a common genetically heterogeneous sensory disorder, occurring in 1 to 3 per 1000 live births. In spite of the extraordinary genetic heterogeneity, variants in GJB2, MT-RNR1, and SLC26A4 genes have been considered as the main reasons of nonsyndromic hearing loss in Chinese population. We developed a rapid multiplex genetic screening system called the SNPscan assay technique which could detect the 115 mutations of the above three genes. This technique is a high-throughput and cost-saving SNP genotyping method. We found that the carrier rate of mutations in the GJB2 gene, MT-RNR1 gene, and SLC26A4 gene was 26.21%, 1.86%, and 25.46% of the patients with nonsyndromic hearing loss, respectively. Using this method, up to 50% of the patients in our study were identified to have hereditary HL caused by mutations in the three genes. It is applicable to not only genetic diagnosis of HL, but also molecular screening of other inherited diseases.

11 Article A rapid automatic processing platform for bead label-assisted microarray analysis: application for genetic hearing-loss mutation detection. 2014

Zhu, Jiang / Song, Xiumei / Xiang, Guangxin / Feng, Zhengde / Guo, Hongju / Mei, Danyang / Zhang, Guohao / Wang, Dong / Mitchelson, Keith / Xing, Wanli / Cheng, Jing. ·1CapitalBio Corporation, Beijing, P. R. China. ·J Lab Autom · Pubmed #23975388.

ABSTRACT: Molecular diagnostics using microarrays are increasingly being used in clinical diagnosis because of their high throughput, sensitivity, and accuracy. However, standard microarray processing takes several hours and involves manual steps during hybridization, slide clean up, and imaging. Here we describe the development of an integrated platform that automates these individual steps as well as significantly shortens the processing time and improves reproducibility. The platform integrates such key elements as a microfluidic chip, flow control system, temperature control system, imaging system, and automated analysis of clinical results. Bead labeling of microarray signals required a simple imaging system and allowed continuous monitoring of the microarray processing. To demonstrate utility, the automated platform was used to genotype hereditary hearing-loss gene mutations. Compared with conventional microarray processing procedures, the platform increases the efficiency and reproducibility of hybridization, speeding microarray processing through to result analysis. The platform also continuously monitors the microarray signals, which can be used to facilitate optimization of microarray processing conditions. In addition, the modular design of the platform lends itself to development of simultaneous processing of multiple microfluidic chips. We believe the novel features of the platform will benefit its use in clinical settings in which fast, low-complexity molecular genetic testing is required.

12 Article Identification of a Novel TECTA mutation in a Chinese DFNA8/12 family with prelingual progressive sensorineural hearing impairment. 2013

Li, Zhengyue / Guo, Yilian / Lu, Yu / Li, Jianzhong / Jin, Zhanguo / Li, Hongbo / Lu, Yanping / Dai, Pu / Han, Dongyi / Cheng, Jing / Yuan, Huijun. ·Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·PLoS One · Pubmed #23936151.

ABSTRACT: Tectorial membrane, an extracellular matrix of the cochlea, plays a crucial role in the transmission of sound to the sensory hair cells. Alpha-tectorin is the most important noncollagenous component of the tectorial membrane and the otolith membrane in the maculae of the vestibular system. Defects in TECTA, the gene encodes alpha-tectorin, are cause of both dominant (DFNA8/12) and recessive (DFNB21) forms of deafness. Here, we report a three-generation Chinese family characterized by prelingual progressive sensorineural hearing impairment. We mapped the disease locus to chromosome 11q23-24 region, overlapping with the DFNA8/12 locus. Sequencing of candidate gene TECTA revealed a heterozygous c.5945C>A substitution in exon 19, causing amino acid substitution of Ala to Asp at a conservative position 1982. The A1982D substitution is consistent with hearing loss in this Chinese family and has not been found in 200 random control chromosomes. To our knowledge, this is the first TECTA mutation identified in Chinese population. Our data provides additional molecular and clinical information for establishing a better genotype-phenotype understanding of DFNA8/12.

13 Article [Clinical and genetic features of a large Chinese family with nonsyndromic autosomal dominant hearing loss]. 2012

Li, Hongbo / Cheng, Jing / Lu, Yu / Li, Zhengyue / Jia, Jingjie / Yuan, Huijun / Han, Dongyi. ·Department of Otorhinolaryngology-Head and Neck Surgery, Institute of Otorhinolaryngology, Chinese PLA General Hospital, Beijing 100853, China. ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #22803410.

ABSTRACT: OBJECTIVE: To investigate the clinical and genetical characteristics of a Chinese family with an autosomal-dominant inherited high-frequency sensorineural hearing loss. METHOD: Pedigree was drawn after investigation. Fifeteen family members were checked up, and detailed audiological examination was performed. RESULT: The proband of the kindred had been diagnosed with senserineural hearing loss. A Chinese family SX-G087 with non-sysdromic hearing loss was ascertained. The inheritance pattern of this family is autosomal dominant based on the investigated information. The affected members showed postlingual, progressive, bilateral moderate to severe sensorineural hearing impairment. The age of onset varied from 20 to 35 years. The hearing loss began at high frequencies, and lower frequencies became involved with increasing age. CONCLUSION: Pedigree analysis suggested an autosomal-dominant inheritance pattern in this family. The information should facilitate linkage analysis and positional cloning for the causative gene of this family.

14 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.

15 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.

16 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.

17 Article Validation of a mobile phone-assisted microarray decoding platform for signal-enhanced mutation detection. 2011

Zhang, Guanbin / Li, Caixia / Lu, Yuan / Hu, Hua / Xiang, Guangxin / Liang, Zhiqing / Liao, Pu / Dai, Pu / Xing, Wanli / Cheng, Jing. ·Medical Systems Biology Research Center, School of Medicine, Tsinghua University, Beijing, China. ·Biosens Bioelectron · Pubmed #21676608.

ABSTRACT: We have established a mobile phone-assisted microarray decoding platform for signal-enhanced mutation detection. A large amount of single-stranded DNA (ssDNA) was obtained by combining symmetric PCR and magnetic isolation, and ssDNA prepared with magnetic bead as label was further allowed to hybridize against the tag-array for decoding purpose. High sensitivity and specificity was achieved with the detection of genomic DNA. When simultaneously genotyping nine common mutations associated with hereditary hearing loss, the detection limit of 1 ng genomic DNA was achieved. Significantly, a mobile phone was also used to record and decode the genotyping results through a custom-designed imaging adaptor and a dedicated mobile phone software. A total of 51 buccal swabs from patients probably with deafness-related mutations were collected and analyzed. The genotyping results were all confirmed by fluorescence-based laser confocal scanning and direct DNA sequencing. This mobile phone-assisted decoding platform provides an effective but economic mutation detection alternative for the future quicker and sensitive detection of virtually any mutation-related diseases in developing and underdeveloped countries.

18 Article [Genetic and audiological characters of a Chinese family with non-syndromic hereditary hearing loss]. 2011

Jin, Zhanguo / Cheng, Jing / Lu, Yu / Li, Jianzhong / Sun, Yi / Yuan, Huijun / Han, Dongyi. ·Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, 100853, China. ·Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi · Pubmed #21563462.

ABSTRACT: OBJECTIVE: To investigate the phenotype and genetic characters of a Chinese family with an autosomal-dominant inherited high-frequency sensorineural hearing loss. METHOD: A Chinese pedigree associated with an autosomal-dominant inherited high-frequency sensorineural hearing loss was investigated. After obtaining informed consent from all study participants medical and audiological examination to rule out any syndromic hearing impairment. Application of microsatellite markers on DFNA 21 loci preliminary screening of 23 genes, data were analyzed by linkage analysis. RESULT: Proband of the family had been diagnosed with high-frequency sensorineural hearing loss. A Chinese family SX-H043 with non-syndromic hearing loss were ascertained. This Chinese family with late onset hearing impairment spanned four generations and comprised 43 members. The mode of inheritance of the families should be autosomal dominant according to the pedigree. Hearing impairment of affected members in family SX-H043 occurred 25 to 50 years descending audiograms. Whole frequencies became involved with increasing age. CONCLUSION: A Chinese family with late-onset high-frequency sensorineural hearing loss were clinically studied. Positive sites were not found in the known deafness loci screening. The information should facilitate future gene scan and linkage analyses for novel relative genes contributing to high-frequency sensorineural hearing loss.

19 Article Identification of two novel missense WFS1 mutations, H696Y and R703H, in patients with non-syndromic low-frequency sensorineural hearing loss. 2011

Sun, Yi / Cheng, Jing / Lu, Yanping / Li, Jianzhong / Lu, Yu / Jin, Zhanguo / Dai, Pu / Wang, Rongguang / Yuan, Huijun. ·Institute of Otolaryngology, Chinese PLA General Hospital, Beijing 100853, China. ·J Genet Genomics · Pubmed #21356526.

ABSTRACT: Non-syndromic low-frequency sensorineural hearing loss (LFSNHL) is an unusual type of hearing loss in which frequencies ≤2000 Hz predominantly are affected. To date, different mutations in two genes, DIAPH1 and WFS1, have been found to be associated with LFSNHL. Here, we report a five-generation Chinese family with postlingual and progressive LFSNHL. We mapped the disease locus to a 2.5 Mb region on chromosome 4p16 between markers SNP_A-2167174 and D4S431, overlapping with the DFNA6/14/38 locus. Sequencing of candidate gene revealed a heterozygous c.2086C>T substitution in exon 8 of WFS1, leading to p.H696Y substitution at the C-terminus of Wolframin (WFS1). In addition, we performed mutational screening of WFS1 in 37 sporadic patients, 7-50 years of age, with LFSNHL. We detected a heterozygous c.2108G>A substitution in exon 8 of WFS1, leading to p.R703H substitution in a patient. The H696 and R703 in WFS1 are highly conserved across species, including human, orangutan, rat, mouse, and frog (Xenopus). Sequence analysis demonstrated the absence of c.2086C>T or c.2108G>A substitutions in the WFS1 genes among 200 unrelated control subjects of Chinese background, supporting the hypothesis that they represent causative mutations, and not rare polymorphisms. Our data provide additional molecular and clinical information for establishing a better genotype-phenotype correlation for LFSNHL.

20 Article Novel missense mutations in MYO7A underlying postlingual high- or low-frequency non-syndromic hearing impairment in two large families from China. 2011

Sun, Yi / Chen, Jing / Sun, Hanjun / Cheng, Jing / Li, Jianzhong / Lu, Yu / Lu, Yanping / Jin, Zhanguo / Zhu, Yuhua / Ouyang, Xiaomei / Yan, Denise / Dai, Pu / Han, Dongyi / Yang, Weiyan / Wang, Rongguang / Liu, Xuezhong / Yuan, Huijun. ·Department of Otolaryngology, Head and Neck Surgery, Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·J Hum Genet · Pubmed #21150918.

ABSTRACT: The myosin VIIA (MYO7A) gene encodes a protein classified as an unconventional myosin. Mutations within MYO7A can lead to both syndromic and non-syndromic hearing impairment in humans. Among different mutations reported in MYO7A, only five led to non-syndromic sensorineural deafness autosomal dominant type 11 (DFNA11). Here, we present the clinical, genetic and molecular characteristics of two large Chinese DFNA11 families with either high- or low-frequency hearing loss. Affected individuals of family DX-J033 have a sloping audiogram at young ages with high frequency are most affected. With increasing age, all test frequencies are affected. Affected members of family HB-S037 present with an ascending audiogram affecting low frequencies at young ages, and then all frequencies are involved with increasing age. Genome-wide linkage analysis mapped the disease loci within the DFNA11 interval in both families. DNA sequencing of MYO7A revealed two novel nucleotide variations, c.652G > A (p.D218N) and c.2011G > A (p.G671S), in the two families. It is for the first time that the mutations identified in MYO7A in the present study are being implicated in DFNA11 in a Chinese population. For the first time, we tested electrocochleography (ECochG) in a DFNA11 family with low-frequency hearing loss. We speculate that the low-frequency sensorineural hearing loss in this DFNA11 family was not associated with endolymphatic hydrops.

21 Article Identification of a novel mutation in POU3F4 for prenatal diagnosis in a Chinese family with X-linked nonsyndromic hearing loss. 2010

Li, Jianzhong / Cheng, Jing / Lu, Yanping / Lu, Yu / Chen, Aiting / Sun, Yi / Kang, Dongyang / Zhang, Xin / Dai, Pu / Han, Dongyi / Yuan, Huijun. ·Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, China. ·J Genet Genomics · Pubmed #21193157.

ABSTRACT: We present the clinical and genetic findings for a Chinese family with X-linked non-syndromic hearing loss in which the affected males showed congenital profound sensorineural hearing impairment. In two affected brothers, the computer tomography of temporal bone showed bilateral dilation of the internal auditory canal with fistulous communication between the lateral canal and the basal cochlear turn, which is consistent with the typical DFNX2 phenotype. A missense mutation (c.647G→A) in the POU3F4 gene caused a substitution from glycine to glutamic acid at position 216 (p.G216E), and this mutation was found to consistently cosegregate with the deafness phenotype in the family. The mutation resulted in the loss of function of the POU3F4 by decreasing the affinity between the protein and DNA, as shown in silico by the structural analysis. Prenatal diagnosis of pregnant proband of this family revealed the c.647G→A mutation in DNA extracted from the amniotic fluid surrounding the fetus. The appropriate use of genetic testing and prenatal diagnosis plays a key role in reducing the recurrence of genetic defects in high-risk families.