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Principal Organizer
Department of Otolaryngology – Head & Neck Surgery, Chinese PLA General Hospital
Co-Organizers
Biochip National Engineering Research Center
Aomaier Genetic Technology Limited Company

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 For enquiries, please contact the Conference Secretariat:

 

Conference Secretariat of ISDGM2009

Genetic Testing Center for Deafness,

Inst. of Otolaryngology,

Chinese PLA General Hospital,

28 FuXing Road, Beijing, 100853, China


Tel: (86) 10-6815 7998 (Mandarin and English)
Fax: (86) 10-6815 7998
Email:
daisy9716@yahoo.com.cn
(Dr. Bing Han)
wjcmu@163.com
(Dr. Guo-Jian Wang)

Lab of Molecular Genetics
Over the past several decades, it has become clear that many human diseases and health status are related either directly or indirectly to genetic background. The majority of diseases have genes corresponding to pathogenesis or susceptibility. The disease process is the result of interaction between relevant genes and the internal/external environment. Research has shown that some cases of hearing loss, including sensorineural, drug-induced, age-related, and noise-induced hearing loss, have relevant pathogenic or susceptibility genes. In 1993, Prof. Sichang Jiang, an academician of the Chinese Academy of Engineering, proposed the establishment of a laboratory for molecular genetics research to serve as the key national unit for otolaryngology in China. Through the joint efforts of specialists over the past decade with a strong commitment to the prevention and treatment of hearing loss, the laboratory has grown into a molecular biology and genetics research base involved in teaching and research with a focus on the pathogenesis and strategies for the prevention of hearing loss. We have completed a systematic study of the pathogenesis, prevention, and treatment of noise- and age-related hearing loss. In addition, we are engaged in research regarding the molecular epidemiology of hearing loss in China, studies of the molecular mechanism and genetic diagnosis of deafness and drug-induced hearing loss.
 
Since 1996, the research groups have traveled to Anhui, Fujian, Guangdong, Guangxi, Guizhou, Hebei, Henan, Hunan, Jiangsu, Jiangxi, Qinghai, Shandong, Shanxi, Sichuang, Yunnan, Zhejiang, Inner Mongolia, and Beijing Daxing district to collected more than 3000 blood samples and clinical data from families with hereditary hearing impairment. We have developed an information collection network and a pedigree resource database for hereditary hearing impairment, laying a solid foundation for our research into the genetics of hearing loss. With the enormous research resources in China, the Laboratory of Molecular Genetics has identified several genes mutations in which are responsible for deafness in many Chinese families with hereditary hearing loss, including COCH, DFNA5, EYA4, MYO7A, POU3F4, PAX3, MITF, and mtDNA A1555G, G7444A.
 
In 2006, we collected data from a five-generation Chinese family GZ-Z052 with X-linked late-onset non-syndromic hearing impairment. The critical interval in family GZ-Z052 spanned a genetic distance of 5.41 cM and a physical distance of about 15.1 Mb. overlapping the previously identified DFN2 locus (Tyson et al. 1996; Manolis et al. 1999; Cui et al. 2004). Based on gene information mapped to the interval from the ENSEMBL website and Morton’s human cochlear cDNA library, 14 candidate genes located in the interval and expressed in the fetal cochlea were selected for mutation screening by sequence analysis. Mutation analysis revealed that a missense mutation (D65N) in the PRPS1 was segregated with deafness in the GZ-Z052 family. As part of an international and domestic collaboration, the Bitner-Glindzicz Group from the London Institute of Child Health, Seidman from Massachusetts Eye and Ear Infirmary, and Prof. Kong Xiangyin from the Institute of Neuroscience of Shanghai Institutes for Biological Sciences provided DNA samples of previously mapped DFN2 families. Subsequent sequencing of PRPS1 in three previously reported DFN2 families led to the identification of three novel PRPS1 missense mutations (A87T, I290T, G306R). The mutated amino acids showed perfect conservation from zebrafish to human. PRPS1 encodes phosphoribosylpyrophosphate synthetase, which catalyzes the phosphoribosylation of ribose-5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for the de novo and salvage pathways of purine and pyrimidine biosynthesis. PRPS1 is the second gene identified on the X chromosome underlying nonsyndromic hearing loss. Enzyme activity assay of phosphoribosyl pyrophosphate synthetase 1 and molecular structure analysis support the causal role of partial loss-of-function mutations in the PRPS1 gene in the nonsyndromic form of sensorineural hearing loss.
 
Ototoxicity is a serious side effect of aminoglycoside antibiotics responsible for irreversible hearing loss. Several recent studies have shown that some patients with aminoglycoside antibiotic-induced deafness (AAID) have a maternally transmitted family history in connection with the A to G homoplasmic mutation at position 1555 (A1555G) in the mtDNA 12S rRNA gene. To determine the correlation between mtDNA mutation and AAID, we launched a research project involving mutational screening in 1996. The mtDNA A1555G Mutation Detection Kit, which was designed to screen for the mtDNA mutation in the heel blood of newborn infants, together with a nationwide mtDNA A1555G gene mutation screening program, have been of significant clinical value in preventing aminoglycoside antibiotic-induced hearing loss. In addition, we identified a deaf family exhibiting both A1555G and G7444A double mutations, and the synergistic effect of these mutations was shown to exacerbate the patient’s hearing loss.
 
Publications:
Han B, Cheng J, Yang SZ, Cao JY, Shen WD, Ji F, Kang DY, Zhang X, Dai P, Yuan HJ. Phenotype and genotype analysis of a Chinese family with prelingual X-linked hereditary hearing impairment. Chin Med J (Engl). 2009 Apr 5;122(7):830-3.
Ouyang XM, Yan D, Yuan HJ, Pu D, Du LL, Han DY, Liu XZ. The genetic bases for non-syndromic hearing loss among Chinese. J Hum Genet. 2009;54(3):131-40.
Liu XZ, Yuan Y, Yan D, Ding EH, Ouyang XM, Fei Y, Tang W, Yuan H, Chang Q, Du LL, Zhang X, Wang G, Ahmad S, Kang DY, Lin X, Dai P. Digenic inheritance of non-syndromic deafness caused by mutations at the gap junction proteins Cx26 and Cx31. Hum Genet. 2009 Feb;125(1):53-62.
Dai P, Yuan Y, Huang D, Zhu X, Yu F, Kang D, Yuan H, Wu B, Han D, Wong LJ. Molecular etiology of hearing impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis. J Transl Med. 2008 Nov 30;6:74.
Yuan Y, Huang D, Yu F, Zhu X, Kang D, Yuan H, Han D, Dai P. A de novo GJB2 (connexin 26) mutation, R75W, in a Chinese pedigree with hearing loss and palmoplantar keratoderma. Am J Med Genet A. 2009 Feb 15;149A(4):689-92.
Dai P, Li Q, Huang D, Yuan Y, Kang D, Miller DT, Shao H, Zhu Q, He J, Yu F, Liu X, Han B, Yuan H, Platt OS, Han D, Wu BL. SLC26A4 c.919-2A>G varies among Chinese ethnic groups as a cause of hearing loss. Genet Med. 2008 Aug;10(8):586-92.
Chen J, Yuan H, Lu J, Liu X, Wang G, Zhu Y, Cheng J, Wang X, Han B, Yang L, Yang S, Yang A, Sun Q, Kang D, Zhang X, Dai P, Zhai S, Han D, Young WY, Guan MX. Mutations at position 7445 in the precursor of mitochondrial tRNA(Ser(UCN)) gene in three maternal Chinese pedigrees with sensorineural hearing loss.Mitochondrion. 2008 Sep;8(4):285-92.
Liu XZ, Angeli S, Ouyang XM, Liu W, Ke XM, Liu YH, Liu SX, Du LL, Deng XW, Yuan H, Yan D. Audiological and genetic features of the mtDNA mutations. Acta Otolaryngol. 2008 Jul;128(7):732-8.
Yuan HJ, Han DY, Sun Q, Yan D, Sun HJ, Tao R, Cheng J, Qin W, Angeli S, Ouyang XM, Yang SZ, Feng L, Cao JY, Feng GY, Wang YF, Dai P, Zhai SQ, Yang WY, He L, Liu XZ. Novel mutations in the vWFA2 domain of COCH in two Chinese DFNA9 families. Clin Genet. 2008 Apr;73(4):391-4.
Cheng J, Han DY, Dai P, Sun HJ, Tao R, Sun Q, Yan D, Qin W, Wang HY, Ouyang XM, Yang SZ, Cao JY, Feng GY, Du LL, Zhang YZ, Zhai SQ, Yang WY, Liu XZ, He L, Yuan HJ. A novel DFNA5 mutation, IVS8+4 A>G, in the splice donor site of intron 8 causes late-onset non-syndromic hearing loss in a Chinese family. Clin Genet. 2007 Nov;72(5):471-7.
Yuan H, Chen J, Liu X, Cheng J, Wang X, Yang L, Yang S, Cao J, Kang D, Dai P, Zhai S, Han D, Young WY, Guan MX. Coexistence of mitochondrial 12S rRNA C1494T and CO1/tRNA(Ser(UCN)) G7444A mutations in two Han Chinese pedigrees with aminoglycoside-induced and non-syndromic hearing loss. Biochem Biophys Res Commun. 2007 Oct 12;362(1):94-100.
Alagramam KN, Miller ND, Adappa ND, Pitts DR, Heaphy JC, Yuan H, Smith RJ. Promoter, alternative splice forms, and genomic structure of protocadherin 15. Genomics. 2007 Oct;90(4):482-92.
Han D, Dai P, Zhu Q, Liu X, Huang D, Yuan Y, Yuan H, Wang X, Qian Y, Young WY,Guan MX. The mitochondrial tRNA(Ala) T5628C variant may have a modifying role in the phenotypic manifestation of the 12S rRNA C1494T mutation in a large Chinese family with hearing loss. Biochem Biophys Res Commun. 2007 Jun 1;357(2):554-60.
Yang SZ, Cao JY, Zhang RN, Liu LX, Liu X, Zhang X, Kang DY, Li M, Han DY, Yuan HJ, Yang WY. Nonsense mutations in the PAX3 gene cause Waardenburg syndrome type I in two Chinese patients. Chin Med J (Engl). 2007 Jan 5;120(1):46-9.
Young WY, Zhao L, Qian Y, Li R, Chen J, Yuan H, Dai P, Zhai S, Han D, Guan MX. Variants in mitochondrial tRNAGlu, tRNAArg, and tRNAThr may influence the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in three Han Chinese families with hearing loss. Am J Med Genet A. 2006 Oct 15;140(20):2188-97.
Dai P, Yuan Y, Huang D, Qian Y, Liu X, Han D, Yuan H, Wang X, Young WY, Guan MX. Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA T1095C mutation in three Chinese families. Biochem Biophys Res Commun. 2006 Sep 15;348(1):200-5.
Dai P, Liu X, Han D, Qian Y, Huang D, Yuan H, Li W, Yu F, Zhang R, Lin H, He Y, Yu Y, Sun Q, Qin H, Li R, Zhang X, Kang D, Cao J, Young WY, Guan MX. Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA mutation in 16 Chinese families: implication for early detection and prevention of deafness. Biochem Biophys Res Commun. 2006 Feb 3;340(1):194-9.
Yuan H, Qian Y, Xu Y, Cao J, Bai L, Shen W, Ji F, Zhang X, Kang D, Mo JQ, Greinwald JH, Han D, Zhai S, Young WY, Guan MX. Cosegregation of the G7444A mutation in the mitochondrial COI/tRNA(Ser(UCN)) genes with the 12S rRNA A1555G mutation in a Chinese family with aminoglycoside-induced and nonsyndromic hearing loss. Am J Med Genet A. 2005 Oct;138A(2):133-40.
Dai P, Yang W, Jiang S, Gu R, Yuan H, Han D, Guo W, Cao J. Correlation of cochlear blood supply with mitochondrial DNA common deletion in presbyacusis. Acta Otolaryngol. 2004 Mar;124(2):130-6.
Alagramam KN, Yuan H, Kuehn MH, Murcia CL, Wayne S, Srisailpathy CR, Lowry RB, Knaus R, Van Laer L, Bernier FP, Schwartz S, Lee C, Morton CC, Mullins RF, Ramesh A, Van Camp G, Hageman GS, Woychik RP, Smith RJ. Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F. Hum Mol Genet. 2001 Aug 1;10(16):1709-18.
Yuan HJ, Yu WY, Shi CH, Sun MJ. Characteristics of recombinant human butyrylcholinesterase. Acta Pharmacology Sinica. 1999 Jan;20(1):74-80.