遗传性非综合征型耳聋的分子机制研究
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摘要
耳聋是最常见的出生缺陷,也是最常见的感觉神经性疾病。据我国2006年残疾人抽样调查结果显示听力残疾(含多重残疾)人共2,780万,并以每年新生3万聋儿的速度增长。要提高防聋治聋的水平,最重要的是要更深入地了解耳聋的病因和发病机理。随着导致耳聋的各种环境因素逐步得到控制,遗传因素在耳聋病因上的重要性日渐突出,研究遗传性耳聋的病因和发病机理,寻找能够预测、减少后代耳聋再发风险及新的治疗方法,对于提高防聋治聋的水平、减少人群中耳聋发病率进而提高我国人口素质有重要的现实和长远意义。本研究正是针对非综合征型遗传性耳聋进行了病因及发病机理的研究,按三个家系分成三部分。
一、X连锁非综合征性聋(DFN2)致病基因(PRPS1)的鉴定及PRPS1突变后的功能研究
本课题组韩冰硕士在前期研究中,鉴定了一个X连锁遗传性非综合征型耳聋家系(GZ-Z052)的致病基因PRPSl,发现第193位核苷酸由鸟嘌呤变为腺嘌呤(c.193G>A),使第65位氨基酸由天冬氨酸变为天冬酰胺(p.D65N)。该基因所在区域(Xq22)与已报道的尚未找到致病基因的三个DFN2家系的致病基因定位区域重叠。为了探索PRPSl是否就是DFN2 (DFNX1)的致病基因,本研究对上述三个家系进行了PRPS1基因的突变筛查,在每一个家系中都发现了突变,分别是：c.259G>A(p.A87T),c.869T>C(p.I290T)和c.916G>A(p.G306R),这几个突变都与各自家系的耳聋表型共分离。来自正常人的DNA样品共1025条X染色体经测序未发现PRPS1基因上述4个位点突变。
对来自GZ-Z052家系8个成员的红细胞和经培养的皮肤成纤维细胞的PRPS用离子对反相HPLC法测定酶活性,发现患者的红细胞和成纤维细胞的酶活性分别是正常对照者酶活性的56%和55%。原核表达的6个PRPS1突变体酶(其中4个为本课题发现的突变,另2个为文献报道的引起PRPS酶活性下降而导致综合征性耳聋的突变位点)进行酶活性检测,发现相对于野生型酶,6个突变体的酶活性都是下降的。本课题发现的4个突变体的酶活性介于野生型和文献报道的引起PRPS1酶活性下而导致综合征性耳聋的突变位点之间。表明DFN2家系是由于PRPS1基因突变后酶活性部分下降所致。
二、X连锁非综合征性聋家系(SX-Z089)致病基因的鉴定及产前基因诊断
经表型及遗传方式分析,将SX-Z089家系判定为X连锁非综合征型耳聋家系。该家系男性患者的颞骨CT检查有典型的DFN3的cT影像学特征。行候选基因筛查时,发现DFN3的致病基因POU3F4基因存在c.647G>A(p.G216E)突变,与家系耳聋表型共分离。该突变在多物种间保守,在110例正常人中未发现上述突变,从而判定该突变为SX-Z089家系的致病基因。对该家系中一名孕18周的携带者取羊水对胎儿DNA进行检测时发现胎儿为c.647G>A(p.G216E)突变半合子,提示该胎儿会复制家系中男性患者的表型。为此家庭提供了明确的遗传咨询依据。
对该家系进行线粒体全序列测序筛查时,发现9名母系成员携带mtDNA961de1T／insC(n)突变,但此突变不与耳聋表型共分离,且家系耳聋已归因于POU3F4基因突变,表明mtDNA 961delT/insC(n)突变不是该家系耳聋的病因。曾有报道mtDNA 961delT/insC(n)突变与药物性耳聋相关,但在SX-Z089家系中多人携带此突变,且有明确氨基糖甙类药物使用史而不出现耳聋。所以,mtDNA 961de lT/insC(n)突变的致病性需进一步确认。
三、常染色体显性非综合征型遗传性耳聋家系(HN-J069)致病基因的定位研究
经表型和遗传方式分析,将HN-J069家系判定为常染色体显性遗传性非综合征型耳聋家系,在该家系中首先对22个已知的常染色体显性遗传性耳聋基因位点进行了连锁分析,排除了这些已知基因为该家系耳聋的致病基因的可能。SNP芯片全基因组连锁分析发现5号染色体160-190cM之间的LOD值接近2,对应于第5号染色体长臂5q33.3-5q35.3区间。下一步拟通过STR遗传标记进行精细定位,可能缩小连锁区域的范围,有望找到一个新的致聋基因。
Hearing impairment is the most common birth defect and sensorineural disorder. Based on the national survey of disabled population in 2006, the total number of hearing impairment in China was 27.8 millions. And the number of newborn with congenital hearing impairment reaches to 20-30 thousands every year. Genetic factors play more important role in the etiology of hearing impairment for the environmental factors are controlled gradually and effectively. To improve the prevention and treatment of hearing impairment and to reduce the number of cases with hearing loss, it is necessary to conduct the study on the cause and molecular mechanism of hearing impairment. In this study, we focus on the molecular cause and mechanism of the hereditary non-syndromic hearing impairment. The study divided into three parts according to three families.
PART1:The confirmation of the causative gene PRPS1 of DFN2 and the functional study of all mutants.
In the previous study of our research group, we found that the candidate gene of GZ-Z052 family with X-linked non-syndromic hearing impairment is PRPS1, with mutation of c.193G>A(p.D65N). The locus (Xq22) of the gene overlapped to that of three previously reported DFN2 families. Mutation screening of PRPS1 gene was carried out in the three DFN2 families and different missense mutation in PRPS1 gene was identified in each family. The mutations are c.259G>A (p.A87T), c.869T>C(p.1290T)and c.916G>A(p.G306R), faithfully segregating with the hearing loss in each family. None of the four mutations were seen in 1025 unrelated control chromosomes, supporting the pathogenicity of the mutations.
The activity of the PRPS of erythrocyte and cultured fibroblast of the affected males of GZ-Z052 family were 56% and 55% of the normal controls. The activity of all of six mutants of PRPS 1 (p.D65N, p.A87T, p.I290T, p.G306R, p.M115T, and p.Q133P) expressed in E. coli BL21, were decreased. The enzyme activity of the four mutants were between that of wild type and p.M115T and p.Q133P, indicating that DFN2 is caused by mutation of PRPS1 gene.
PART 2:Identification of causative gene of SX-Z089 family and prenatal diagnosis conducted in this family
SX-Z089 family exhibits X-linked non-syndromic hearing impairment. The affected males had typical temporal bone CT imaging of DFN3, e.g, bilateral dilation of the internal auditory canals and with a fistulous communication between its lateral aspect and the basal turn of the cochlea. A c.647G>A (p.G216E) mutation in POU3F4 gene was found segregating with the phenotype of the family. The G216 is conserved from clawed frog to human. The mutation was absent in 110 normal controls. A hemizygotic mutation of c.647G>A in POU3F4 gene was found in the DNA sample of the amniotic fluid in prenatal diagnosis, indicating that the fetus will copy the phenotype of the affected males of the family.
Nine maternal members of SX-Z089 family carried mtDNA 961delT/insC(n) mutation. This mutation do not segregate with the phenotype of the family. The mtDNA 961delT/insC(n) mutation is unlikely the causative mutation of the family. The mtDNA 961delT/insC(n) had been reported to associate with the aminoglycoside-induced hearing loss. However, in SX-Z089 family some members with mtDNA 961delT/insC(n) mutation did not have hearing loss even had a history of aminoglycoside use. The role of mtDNA 961delT/insC(n) in aminoglycoside-induced hearing loss remains to be confirmed.
PART 3:Gene mapping of HN-J069 family with autosomal dominant hereditary non-syndromic hearing impairment
We have collected a family with autosomal dominant non-syndromic hereditary hearing loss (DFNA) from HeNan province. Twenty-two DFNA loci with known genes had been ruled out by linkage analysis using the STR markers near the known DFNA genes in family HN-J069. We have mapped the disease locus to 30cM interval on chromosome 5, between 5q33.3 and 5q35.3, by genome wide SNP typing. Fine mapping will be conducted with STR markers in this interval. This will lead to identification of a new deafness gene in this family.
一、X连锁非综合征性聋(DFN2)致病基因(PRPS1)的鉴定及PRPS1突变后的功能研究
本课题组韩冰硕士在前期研究中,鉴定了一个X连锁遗传性非综合征型耳聋家系(GZ-Z052)的致病基因PRPSl,发现第193位核苷酸由鸟嘌呤变为腺嘌呤(c.193G>A),使第65位氨基酸由天冬氨酸变为天冬酰胺(p.D65N)。该基因所在区域(Xq22)与已报道的尚未找到致病基因的三个DFN2家系的致病基因定位区域重叠。为了探索PRPSl是否就是DFN2 (DFNX1)的致病基因,本研究对上述三个家系进行了PRPS1基因的突变筛查,在每一个家系中都发现了突变,分别是：c.259G>A(p.A87T),c.869T>C(p.I290T)和c.916G>A(p.G306R),这几个突变都与各自家系的耳聋表型共分离。来自正常人的DNA样品共1025条X染色体经测序未发现PRPS1基因上述4个位点突变。
对来自GZ-Z052家系8个成员的红细胞和经培养的皮肤成纤维细胞的PRPS用离子对反相HPLC法测定酶活性,发现患者的红细胞和成纤维细胞的酶活性分别是正常对照者酶活性的56%和55%。原核表达的6个PRPS1突变体酶(其中4个为本课题发现的突变,另2个为文献报道的引起PRPS酶活性下降而导致综合征性耳聋的突变位点)进行酶活性检测,发现相对于野生型酶,6个突变体的酶活性都是下降的。本课题发现的4个突变体的酶活性介于野生型和文献报道的引起PRPS1酶活性下而导致综合征性耳聋的突变位点之间。表明DFN2家系是由于PRPS1基因突变后酶活性部分下降所致。
二、X连锁非综合征性聋家系(SX-Z089)致病基因的鉴定及产前基因诊断
经表型及遗传方式分析,将SX-Z089家系判定为X连锁非综合征型耳聋家系。该家系男性患者的颞骨CT检查有典型的DFN3的cT影像学特征。行候选基因筛查时,发现DFN3的致病基因POU3F4基因存在c.647G>A(p.G216E)突变,与家系耳聋表型共分离。该突变在多物种间保守,在110例正常人中未发现上述突变,从而判定该突变为SX-Z089家系的致病基因。对该家系中一名孕18周的携带者取羊水对胎儿DNA进行检测时发现胎儿为c.647G>A(p.G216E)突变半合子,提示该胎儿会复制家系中男性患者的表型。为此家庭提供了明确的遗传咨询依据。
对该家系进行线粒体全序列测序筛查时,发现9名母系成员携带mtDNA961de1T／insC(n)突变,但此突变不与耳聋表型共分离,且家系耳聋已归因于POU3F4基因突变,表明mtDNA 961delT/insC(n)突变不是该家系耳聋的病因。曾有报道mtDNA 961delT/insC(n)突变与药物性耳聋相关,但在SX-Z089家系中多人携带此突变,且有明确氨基糖甙类药物使用史而不出现耳聋。所以,mtDNA 961de lT/insC(n)突变的致病性需进一步确认。
三、常染色体显性非综合征型遗传性耳聋家系(HN-J069)致病基因的定位研究
经表型和遗传方式分析,将HN-J069家系判定为常染色体显性遗传性非综合征型耳聋家系,在该家系中首先对22个已知的常染色体显性遗传性耳聋基因位点进行了连锁分析,排除了这些已知基因为该家系耳聋的致病基因的可能。SNP芯片全基因组连锁分析发现5号染色体160-190cM之间的LOD值接近2,对应于第5号染色体长臂5q33.3-5q35.3区间。下一步拟通过STR遗传标记进行精细定位,可能缩小连锁区域的范围,有望找到一个新的致聋基因。
Hearing impairment is the most common birth defect and sensorineural disorder. Based on the national survey of disabled population in 2006, the total number of hearing impairment in China was 27.8 millions. And the number of newborn with congenital hearing impairment reaches to 20-30 thousands every year. Genetic factors play more important role in the etiology of hearing impairment for the environmental factors are controlled gradually and effectively. To improve the prevention and treatment of hearing impairment and to reduce the number of cases with hearing loss, it is necessary to conduct the study on the cause and molecular mechanism of hearing impairment. In this study, we focus on the molecular cause and mechanism of the hereditary non-syndromic hearing impairment. The study divided into three parts according to three families.
PART1:The confirmation of the causative gene PRPS1 of DFN2 and the functional study of all mutants.
In the previous study of our research group, we found that the candidate gene of GZ-Z052 family with X-linked non-syndromic hearing impairment is PRPS1, with mutation of c.193G>A(p.D65N). The locus (Xq22) of the gene overlapped to that of three previously reported DFN2 families. Mutation screening of PRPS1 gene was carried out in the three DFN2 families and different missense mutation in PRPS1 gene was identified in each family. The mutations are c.259G>A (p.A87T), c.869T>C(p.1290T)and c.916G>A(p.G306R), faithfully segregating with the hearing loss in each family. None of the four mutations were seen in 1025 unrelated control chromosomes, supporting the pathogenicity of the mutations.
The activity of the PRPS of erythrocyte and cultured fibroblast of the affected males of GZ-Z052 family were 56% and 55% of the normal controls. The activity of all of six mutants of PRPS 1 (p.D65N, p.A87T, p.I290T, p.G306R, p.M115T, and p.Q133P) expressed in E. coli BL21, were decreased. The enzyme activity of the four mutants were between that of wild type and p.M115T and p.Q133P, indicating that DFN2 is caused by mutation of PRPS1 gene.
PART 2:Identification of causative gene of SX-Z089 family and prenatal diagnosis conducted in this family
SX-Z089 family exhibits X-linked non-syndromic hearing impairment. The affected males had typical temporal bone CT imaging of DFN3, e.g, bilateral dilation of the internal auditory canals and with a fistulous communication between its lateral aspect and the basal turn of the cochlea. A c.647G>A (p.G216E) mutation in POU3F4 gene was found segregating with the phenotype of the family. The G216 is conserved from clawed frog to human. The mutation was absent in 110 normal controls. A hemizygotic mutation of c.647G>A in POU3F4 gene was found in the DNA sample of the amniotic fluid in prenatal diagnosis, indicating that the fetus will copy the phenotype of the affected males of the family.
Nine maternal members of SX-Z089 family carried mtDNA 961delT/insC(n) mutation. This mutation do not segregate with the phenotype of the family. The mtDNA 961delT/insC(n) mutation is unlikely the causative mutation of the family. The mtDNA 961delT/insC(n) had been reported to associate with the aminoglycoside-induced hearing loss. However, in SX-Z089 family some members with mtDNA 961delT/insC(n) mutation did not have hearing loss even had a history of aminoglycoside use. The role of mtDNA 961delT/insC(n) in aminoglycoside-induced hearing loss remains to be confirmed.
PART 3:Gene mapping of HN-J069 family with autosomal dominant hereditary non-syndromic hearing impairment
We have collected a family with autosomal dominant non-syndromic hereditary hearing loss (DFNA) from HeNan province. Twenty-two DFNA loci with known genes had been ruled out by linkage analysis using the STR markers near the known DFNA genes in family HN-J069. We have mapped the disease locus to 30cM interval on chromosome 5, between 5q33.3 and 5q35.3, by genome wide SNP typing. Fine mapping will be conducted with STR markers in this interval. This will lead to identification of a new deafness gene in this family.
引文
[1]Hilgert N, Smith RJ, Van Camp G, et al. Forty-six genes causing nonsyn-dromic hearing impairment:Which ones should be analyzed in DNA diagnostics. Mutation Research.2009,681(2-3):189-196.
[2]Morton CC, Nance WE. Newborn hearing screening-a silent revolution. N Engl J Med.2006,354(20):2151-2164.
[3]孙喜斌,于丽玫,曲成毅等.中国听力残疾构成特点及康复对策.中国听力语言康复科学杂志.2008,27(2)：21-24.
[4]Smith RJH, Camp GV. Deafness and Hereditary Hearing Loss Overview. In NCBI》 Bookshelf》 GeneReviews》 Initial Posting:February 14,1999. Last Revision:December 2,2008.
[5]Petersen MB, Wang Q, Willems PJ. Sex-linked deafness. Clin Genet.2008, 73(1):14-23.
[6]Lezirovitz K, Braga MC, Thiele-Aguiar RS, et al. A novel autosomal dominant deaf-ness locus (DFNA58) maps to 2p12-p21. Clin Genet.2009,75(5):490-493
[7]Chatterjee A, Jalvi R, Pandey N, et al. A novel locus DFNA59 for autosomal dominant non-syndromic hearing loss maps at chromosome 11p14.2-q12.3. Hum Genet.2009, 124(6):669-675.
[8]Collins FS, Gelehrter TD著.孙开来,赵彦艳,熊第志译.医学遗传学原理.北京：科学出版社.2001：190～197.
[1]Petersen MB, Wang Q, Willems PJ. Sex-linked deafness. Clin Genet.2008, 73(1):14-23.
[2]Tyson J, Bellman S, Newton V, et al. Mapping of DFN2 to Xq22. Hum Mol Genet.1996,5(12):2055-2060.
[3]Manolis EN, Eavey RD, Sangwatanaroj S, et al. Hereditary postlingual sensorineural hearing lossmapping to chromosome Xq21. Am J Otol.1999, 20(5):621-626.
[4]Cui B, Zhang H, Lu Y, et al. Refinement of the locus for non-syndromic sensorineural deafness (DFN2). J Genet.2004,83(1):35-38.
[5]彭岚,刘义钦,刘俊凡.离子对反相HPLC测定人红细胞PRPP合成酶活性.生物化学杂志.1997,13(1)：113-115.
[6]Torres RJ, Mateos FA, Puig JG, et al. A simplified method for the determination of phosphoribosylpyrophosphate synthetase activity in hemolysates. Clin Chim Acta.1994,224 (1):55-63.
[7]Sakuma R, Nishina T, Yamanaka H, et al. Phosphoribosylpyrophosphate synthetase in human erythrocytes:assay and kinetic studies using highper-formance liquid chromatography. Clin Chim Acta.1991,203((2-3): 143-152.
[8]鄂征.组织培养技术及其在医学研究中的应用.北京中国协和医科大学出版社.2004,第一版：128,161.
[9]Kim HJ, Sohn KM, Shy ME, et al. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5). Am J Hum Genet.2007,81(3):552-558.
[10]De Brouwer APM, Williams KL, Duley JA, et al. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet.2007,81(3): 507-518.
[11]Tang WY, Li XW, Zhu ZQ, et al. Expression, purification, crystallization and preliminary X-ray diffraction analysis of human phosphoribosyl-pyrophosphate synthetase 1 (PRS1). Acta Crystallogr.2006, F 62:432-434.
[12]Li S, Lu Y, Peng B, et al. Crystal structure of human phosphoribosyl-pyrophosphate synthetase 1 reveals a novel allosteric site. Biochem J.2007, 401(1):39-47.
[13]Liu Honglin, Peng Xiaohui, Zhao Fang, et al. N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1. Biochemical and Biophysical Research Communications.2009, 379(4):1120-1125.
[14]Arnold K, Bordoli L, Kopp J, et al.. The SWISS-MODEL Workspace:A web-based environment for protein structure homology modelling. Bioinformatics.2006,22(2):195-201.
[15]Schwede T, Kopp J, Guex N, et al. SWISS-MODEL:an automated protein homology-modeling server. Nucleic Acids Research.2003,31(13): 3381-3385.
[16]Guex N and Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer:An environment for comparative protein modelling. Electrophoresis.1997, 18(15):2714-2723.
[17]Tom Strachan, Andrew P Read.人类分子遗传学(原书第三版)／(英).孙开来译.北京科学出版社.2007,第一版：548,550.
[18]Becker MA. Phosphoribosylpyrophosphate synthetase and the regulation of phosphoribosylpyrophosphate production in human cells. Prog Nucleic Acid Res Mol Biol.2001,69:115-148.
[19]Roessler BJ, Palella TD, Heidler S, et al. Identification of distinct PRPS1 mutations in two patients with X-linked phosphoribosylpyrophosphate synthetase superactivity. Adv Exp Med Biol.1991,309B:125-128.
[20]Roessler BJ, Nosal JM, Smith PR, et al. Human X-linked phosphoribosyl-pyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. J Biol Chem.1993,268(35):26476-26481.
[21]Becker MA, Smith PR, Taylor W, et al. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest.1995,96(5):2133-2141.
[22]Garcia-Pavia P, Torres RJ, Rivero M, et al. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis & Rheumatism.2003,48(7):2036-2041.
[23]Becker MA. Phosphoribosylpyrophosphate synthetase (PRPS) superactivity. Available at http://www.ncbi.nlm.gov/Books:GeneReviews. Initial Posting: September 23,2008.
[1]International Organization for Standardization Acoustics:reference zero for the calibration of audiometric equipment-part 1:reference equivalent threshold sound pressure levels for pure tones and supra-aural earphones, BSEN ISO 389-1. International Organization for Standardization, Geneva, Switzerland,2000.
[2]International Organization for Standardization Acoustics:audiometric test methods, Ⅰ:basic pure tone air and bone conduction threshold audiometry, ISO 8253-1. International Organization for Standardization, Geneva, Switzerland,1998.
[3]Lofrano-Porto A, Barra GB, Nascimento PP, et al. Pendred syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene. Arq Bras Endocrinol Metabol.2008,52(8):1296-303.
[4]Chee NWC, Suhailee S, Goh J. Clinics in diagnostic imaging (Ⅲ). Singapore Med J.2006,47(9):822-825.
[5]Wallis C, Ballo R, Wallis G., et al. X-linked mixed deafness with stapes fixation in a Mauritian kindred:linkage to Xq probe pDP34. Genomics. 1988,3(4):299-301.
[6]Brunner HG, Bennekom AV, Lambermon EM, et al. The gene for X-linked progressive mixed deafness with perilymphatic gusher during stapes surgery (DFN3) is linked to PGK. Hum Genet,1988,80(4):337-340.
[7]De Kok YJ, Van der Maarel SM, Bitner-Glindzicz M, et al. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4. Science.1995,267(5198):685-688.
[8]Wang QJ, Li QZ, Rao SQ, et al. A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family. Laryngoscope.2006,116(6):944-950.
[9]Lalwani AK, Brister JR, Fex J, et al. A new non-syndromic X-linked sensori-neural hearing impairment linked to Xp21.2. Am J Hum Genet.1994,55(4): 685-694.
[10]Pfister MH, Apaydin F, Turan O, et al. A second family with non-syndromic sensorineural hearing loss linked to Xp21.2:refinement of the DFN4 locus within DMD. Genomics.1998,53(3):377-382.
[11]Del Castillo I, Villamar M, Sarduy M, et al. A novel locus for nonsyndro-mic sensorineural deafness (DFN6) maps to chromosome Xp22. Hum Mol Genet,1996,5(9):1383-1387.
[12]赵辉,李荣华,王秋菊等.母系遗传药物性聋与非综合征性聋大家系与基因突变的研究.中华耳科学杂志.2005,3(1)：1-12.
[13]Mathis JM, Simmons DM, He X, et al. Brain 4:a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. EMBO J.1992,11(7):2551-2561.
[14]Klemm JD, Rould MA, Aurora R, et al. Crystal structure of the Oct-1 POU domain bound to an octamer site:DNA recognition with tethered DNA-binding modules. Cell.1994,77 (1):21-32.
[15]Nussbaum RM, McInnes RR, Willard HF. THOMPSON & THOMPSON Genetics in Medicine.6th edition.英文影印本,北京大学医学出版社.2007：360-369.
[16]. Bitner-Glindzicz M, Tumpenny P, Hoglund P, et al. Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3. Hum Mol Genet.1995,4 (8):1467-1469.
[17]De Kok YJ, Cremers CW, Ropers HH, et al. The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases:identification of a somatic mosaicism for a POU3F4 missense mutation. Hum Mutat.1997, 10(3):207-211.
[18]Friedman RA, Bykhovskaya Y, Tu G, et al. Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher. Ann Otol Rhinol Laryngol.1997,106(4):320-325.
[19]Hagiwara H, Tamagawa Y, Kitamura K, et al. A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3). Laryngoscope.1998,108(10):1544-1547.
[20]Cremers FP, Cremers CW, Ropers HH. The ins and outs of X-linked deafness type 3. Adv Otorhinolaryngol.2000,56:184-195.
[21]Vore AP, Chang EH, Hoppe JE, et al. Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked non-syndromic deafness. Arch Otolaryngol Head Neck Surg.2005,131(12):1057-1063.
[22]Lee HK, Song MH, Kang M, et al. Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein. Physiol Genomics.2009,39(3):195-201.
[23]Marlin S, Moizard MP, David A, et al. Phenotype and genotype in females with POU3F4 mutations. Clin Genet.2009,76(6):558-563.
[24]Lee HK, Lee SH, Lee KY, et al. Novel POU3F4 mutations and clinical features of DFN3 patients with cochlear implants. Clin Genet.2009,75(5): 572-575.
[25]De Kok YJM, Merkx GFM, van der Maarel SM, et al. A duplication/ paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene. Hum Mol Genet.1995,4(11):2145-2150.
[26]De Kok YJ, Vossenaar ER, Cremers CW, et al. Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4. Hum Mol Genet.1996,5(9): 1229-1235.
[27]Marazita ML, Ploughman LM, Rawlings B, et al. Genetic epidemiological studies of early-onset deafness in the U.S. school-age population. Am J Med Genet.1993,46(5):486-491.
[28]Li Z, Li R, Chen J, et al. Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet.2005,117(1):9-15.
[29]Yuan H, Qian Y, Xu Y, et al. 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 nonsyn-dromic hearing loss. Am J Med Genet.2005,138A(2):133-140.
[30]Dai P, Liu X, Han D, et al. 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.2006,340(1):194-199.
[31]Wang Q, Li QZ, Han D, et al. Clinical and molecular analysis of a four-generation Chinese family with amino-glycoside-induced and non-syndromic hearing loss associated with the mitochondrial 12S rRNA C1494T mutation. Biochem Biophys Res Commun.2006,340(2):583-588.
[32]Zhu Y, Qian Y, Tang X, et al. Aminoglycoside-induced and non-syndromic hearing loss is associated with the G7444A mutation in the mitochondrial COI/tRNASer (UCN) genes in two Chinese families. Biochem Biophys Res Commun.2006,342(3):843-850.
[33]Bacino C, Prezant TR, Bu X, et al. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics.1995,5(3):165-172.
[34]Casano RA, Johnson DF, Bykhovskaya Y, et al. Inherited susceptibility to aminoglycoside ototoxicity:genetic heterogeneity and clinical implications. Am J Otolaryngol.1999,20(3):151-156.
[35]Yoshida M, Shintani T, Hirao M, et al. Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA. ORL J Otorhinolaryngol Relat Spec.2002,64(3):219-222.
[36]Kobayashi K, Oquci T, Asamura K, et al. Genetic features, clinical phenotypes, and prevalence of sensorineural hearing loss associated with the 961delT mitochondrial mutation. Auris Nasus Larynx.2005,32(2): 119-124.
[37]Bae JW, Lee KY, Choi SY, et al. Molecular analysis of mitochondrial gene mutations in Korean patients with non-syndromic hearing loss. Int J Mol Med.2008,22(2):175-180.
[1]Nussbaum RM, McInnes RR, Willard HF. THOMPSON & THOMPSON Genetics in Medicine.6th edition.英文影印本,北京大学医学出版社.2007：360-369.
[2]Su MC, Yang JJ, Su CC, et al. Identification of novel variants in the Myosin VIIA gene of patients with non-syndromic hearing loss from Taiwan. Int J Pediatr Otorhinolaryngol. Int J Pediatr Otorhinolaryngol.2009,73(6):811-5.
[3]Weil D, Blanchard S, Kaplan J, et al. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature.1995,374(6517):60-61.
[4]Hilgert N, Smith RJ, Van Camp G. Forty-six genes causing non-syndromic hearing impairment:Which ones should be analyzed in DNA diagnostics. (2009)Mutat Res.2009,681(2-3):189-96.
[5]Tantz D. Hyperriability of simple sequences as a general source for polymorphic DNA markers. Nucleic Acids Research.1989,17(16): 67632-6771.
[6]邓昊,何云贵,夏家辉.微卫星荧光标记基因组扫描.生命科学研究.2000,4(2)(专辑)：18-23.
[1]Becker MA. Phosphoribosylpyrophosphate synthetase and the regulation of phosphorribosylpyrophosphate production in human cells. Prog Nucleic Acid Res Mol Biol; 2001,69:115-148.
[2]Becker MA, Heidler SA, Bell GI, et al. Cloning of cDNAs for human phosphoribosylpyro-phosphate synthetases 1 and 2 and X chromosome localization of PRPS1 and PRPS2 genes. Genomics.1990,8 (3):555-561.
[3]Taira M, Iizasa T, Shimada H, et al. A human testis-specific mRNA for phosphoribosylpyro-phosphate synthetase that initiates from a non-AUG codon. J Biol Chem.265 (27):16491-16497.
[4]Taira M, Iizasa T, Yamada K,et al. Tissue-differential expression of two distinct genes for phosphoribosylpyrophosphate synthetase and existence of the testis-specific transcript. BiochimBiophys Acta.1989,1007(2):203-208.
[5]Becker MA, Ahmed M. Cell type-specific differential expression of human PRPP syntherase (PRPS) genes. Adv Exp Med Biol.2000,486(1):5-10.
[6]Ishizuka T, Ahmad I, Kita K, et al. The human phosphoribosylpyrophosphate synthetaseassociated protein 39 gene (PRPSAP1) is located in the chromosome region 17q24-q25. Genomics.1996,33(2):332-334.
[7]Katashima R, Iwahana H, Fujimura M, et al. Assignment of the human phosphoribosylpyrophosphate synthetase-associated protein 41 gene (PRPSAP2) to 17p11.2-p12. Genomics.1998,54(1):180-181.
[8]Li S, Lu Y, Peng B, et al. Crystal structure of human phosphoribosyl-pyrophosphate synthetase 1 reveals a novel allosteric site. J Biochem.2007, 401(1):39-47.
[9]Fox IH, Kelley WN. Human phosphoribosylpyrophosphate synthetase: distribution, purification, and properties. J Biol Chem.1971,246(18): 5739-5748.
[10]Becker MA, Kostel PJ, Meyer LJ. Human phosphoribosylpyrophosphate synthetase:comparison of purified normal and mutant enzymes. J Biol Chem.1975,250(17):6822-6830.
[11]Tatibana M, Kita K, Taira M, et al. Mammalian phosphoribosyl-pyrophosphate synthetase. Advan Enzyme Regul.1995,35:229-249.
[12]Roessler BJ, Palella TD, Heidler S, et al. Identification of distinct PRPS1 mutations in two patients with X-linked phosphoribosylpyrophosphate synthetase superactivity. Adv Exp Med Biol.1991,309B:125-128.
[13]Roessler BJ, Nosal JM, Smith PR, et al. Human X-linked phosphoribosyl-pyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. J Biol Chem.1993,268(35):26476-26481.
[14]Becker MA, Smith PR, Taylor W, et al. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest.1995,96(5):2133-2141.
[15]Garcia-Pavia P, Torres RJ, Rivero M, et al. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis & Rheumatism.2003,48(7):2036-2041.
[16]Kim HJ, Sohn KM, Shy ME, et al. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5). Am J Hum Genet.2007,81(3):552-558.
[17]De Brouwer APM, Williams KL, Duley JA, et al. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet.2007,81(3): 507-518.
[18]Liu X, Han D, Li J, et al. Loss-of-function mutations in the PRPS1 gene cause a type of non-syndromic X-linked sensorineural deafness, DFN2. Am J Hum Genet.2010,86(1):65-71.
[19]Becker MA. Phosphoribosylpyrophosphate synthetase (PRS) superactivity. Available at http://www.ncbi.nlm.gov/Books:GeneReviews. Initial Posting: September 23,2008.
[20]Zoref E, DeVries A, and Sperling A. Mutant feedback-resistant phospho-ribosylpyrophosphate synthetase associated with purine overproduction and gout. J Clin Invest.1975,56(5):1093-1099.
[21]Sperling O, Persky-Brosh S, Boer P, et al. Human erythrocyte phospho-ribosylpyrophosphate synthetase mutationally altered in regulatory properties. Biochem Med.1973,7(3):389-395.
[22]Becker MA, Puig JG, Mateos FA, et al.. Inherited superactivity of phosphoribosylpyrophosphate synthetase:association of uric acid overproduction and sensorineural deafness. Am J Med.1988,85(3): 383-390.
[23]Becker MA, Losman MJ, Wilson J, et al. Superactivity of phospho-ribosylpyrophosphate synthetase due to altered regulation by nucleotide inhibitors and inorganic phosphate. Biochim Biophys Acta.1986,882(2): 168-176.
[24]Becker MA, Losman MJ, Itkin P, et al. Gout with superactive phospho-ribosylpyrophosphate synthetase due to increased enzyme catalytic rate. J Lab Clin Med.1982,99(4):495-511.
[25]Becker MA, Losman MJ, Rosenberg AL, et al. Phosphoribosyl-pyrophosphate synthetase superactivity, A study of five patients with catalytic defects in the enzyme. Arthritis Rheum.1986,29(7):880-888.
[26]Akaoka I, Fujimori S, Kamatani N, et al. A gouty family with increased phosphoribosylpyrophosphate synthetase activity:case reports, family studies, and kinetic studies of the abnormal enzyme. J Rheumatol.1981, 8(4):563-574.
[27]Nishida Y, Akaoki I, and Horiuchi Y. Altered isoelectric property of a superactive 5-phosphoribosyl-l-pyrophosphate (PRPP) synthetase in a patient with clinical gout. Biochem Med.1981,26(3):387-394.
[28]Becker MA, Raivio KO, Bakay B, et al. Variant human phospho-ribosylpyrophosphate synthetase altered in regulatory and catalytic functions. J Clin Invest.1980,65(1):109-120.
[29]Losman MJ, Rimon D, Kim M, et al. Selective expression of phospho-ribosylpyrophosphate synthetase superactivity in human lymphoblast lines. J Clin Invest.1985,76(4):1657-1664.
[30]Becker MA. Patterns of phosphoribosylpyrophosphate and ribose-5-phosphate concentration and generation in fibroblasts from patients with gout and purine overproduction. J Clin Invest.1976,57(2):308-318.
[2]Morton CC, Nance WE. Newborn hearing screening-a silent revolution. N Engl J Med.2006,354(20):2151-2164.
[3]孙喜斌,于丽玫,曲成毅等.中国听力残疾构成特点及康复对策.中国听力语言康复科学杂志.2008,27(2)：21-24.
[4]Smith RJH, Camp GV. Deafness and Hereditary Hearing Loss Overview. In NCBI》 Bookshelf》 GeneReviews》 Initial Posting:February 14,1999. Last Revision:December 2,2008.
[5]Petersen MB, Wang Q, Willems PJ. Sex-linked deafness. Clin Genet.2008, 73(1):14-23.
[6]Lezirovitz K, Braga MC, Thiele-Aguiar RS, et al. A novel autosomal dominant deaf-ness locus (DFNA58) maps to 2p12-p21. Clin Genet.2009,75(5):490-493
[7]Chatterjee A, Jalvi R, Pandey N, et al. A novel locus DFNA59 for autosomal dominant non-syndromic hearing loss maps at chromosome 11p14.2-q12.3. Hum Genet.2009, 124(6):669-675.
[8]Collins FS, Gelehrter TD著.孙开来,赵彦艳,熊第志译.医学遗传学原理.北京：科学出版社.2001：190～197.
[1]Petersen MB, Wang Q, Willems PJ. Sex-linked deafness. Clin Genet.2008, 73(1):14-23.
[2]Tyson J, Bellman S, Newton V, et al. Mapping of DFN2 to Xq22. Hum Mol Genet.1996,5(12):2055-2060.
[3]Manolis EN, Eavey RD, Sangwatanaroj S, et al. Hereditary postlingual sensorineural hearing lossmapping to chromosome Xq21. Am J Otol.1999, 20(5):621-626.
[4]Cui B, Zhang H, Lu Y, et al. Refinement of the locus for non-syndromic sensorineural deafness (DFN2). J Genet.2004,83(1):35-38.
[5]彭岚,刘义钦,刘俊凡.离子对反相HPLC测定人红细胞PRPP合成酶活性.生物化学杂志.1997,13(1)：113-115.
[6]Torres RJ, Mateos FA, Puig JG, et al. A simplified method for the determination of phosphoribosylpyrophosphate synthetase activity in hemolysates. Clin Chim Acta.1994,224 (1):55-63.
[7]Sakuma R, Nishina T, Yamanaka H, et al. Phosphoribosylpyrophosphate synthetase in human erythrocytes:assay and kinetic studies using highper-formance liquid chromatography. Clin Chim Acta.1991,203((2-3): 143-152.
[8]鄂征.组织培养技术及其在医学研究中的应用.北京中国协和医科大学出版社.2004,第一版：128,161.
[9]Kim HJ, Sohn KM, Shy ME, et al. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5). Am J Hum Genet.2007,81(3):552-558.
[10]De Brouwer APM, Williams KL, Duley JA, et al. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet.2007,81(3): 507-518.
[11]Tang WY, Li XW, Zhu ZQ, et al. Expression, purification, crystallization and preliminary X-ray diffraction analysis of human phosphoribosyl-pyrophosphate synthetase 1 (PRS1). Acta Crystallogr.2006, F 62:432-434.
[12]Li S, Lu Y, Peng B, et al. Crystal structure of human phosphoribosyl-pyrophosphate synthetase 1 reveals a novel allosteric site. Biochem J.2007, 401(1):39-47.
[13]Liu Honglin, Peng Xiaohui, Zhao Fang, et al. N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1. Biochemical and Biophysical Research Communications.2009, 379(4):1120-1125.
[14]Arnold K, Bordoli L, Kopp J, et al.. The SWISS-MODEL Workspace:A web-based environment for protein structure homology modelling. Bioinformatics.2006,22(2):195-201.
[15]Schwede T, Kopp J, Guex N, et al. SWISS-MODEL:an automated protein homology-modeling server. Nucleic Acids Research.2003,31(13): 3381-3385.
[16]Guex N and Peitsch MC. SWISS-MODEL and the Swiss-PdbViewer:An environment for comparative protein modelling. Electrophoresis.1997, 18(15):2714-2723.
[17]Tom Strachan, Andrew P Read.人类分子遗传学(原书第三版)／(英).孙开来译.北京科学出版社.2007,第一版：548,550.
[18]Becker MA. Phosphoribosylpyrophosphate synthetase and the regulation of phosphoribosylpyrophosphate production in human cells. Prog Nucleic Acid Res Mol Biol.2001,69:115-148.
[19]Roessler BJ, Palella TD, Heidler S, et al. Identification of distinct PRPS1 mutations in two patients with X-linked phosphoribosylpyrophosphate synthetase superactivity. Adv Exp Med Biol.1991,309B:125-128.
[20]Roessler BJ, Nosal JM, Smith PR, et al. Human X-linked phosphoribosyl-pyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. J Biol Chem.1993,268(35):26476-26481.
[21]Becker MA, Smith PR, Taylor W, et al. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest.1995,96(5):2133-2141.
[22]Garcia-Pavia P, Torres RJ, Rivero M, et al. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis & Rheumatism.2003,48(7):2036-2041.
[23]Becker MA. Phosphoribosylpyrophosphate synthetase (PRPS) superactivity. Available at http://www.ncbi.nlm.gov/Books:GeneReviews. Initial Posting: September 23,2008.
[1]International Organization for Standardization Acoustics:reference zero for the calibration of audiometric equipment-part 1:reference equivalent threshold sound pressure levels for pure tones and supra-aural earphones, BSEN ISO 389-1. International Organization for Standardization, Geneva, Switzerland,2000.
[2]International Organization for Standardization Acoustics:audiometric test methods, Ⅰ:basic pure tone air and bone conduction threshold audiometry, ISO 8253-1. International Organization for Standardization, Geneva, Switzerland,1998.
[3]Lofrano-Porto A, Barra GB, Nascimento PP, et al. Pendred syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene. Arq Bras Endocrinol Metabol.2008,52(8):1296-303.
[4]Chee NWC, Suhailee S, Goh J. Clinics in diagnostic imaging (Ⅲ). Singapore Med J.2006,47(9):822-825.
[5]Wallis C, Ballo R, Wallis G., et al. X-linked mixed deafness with stapes fixation in a Mauritian kindred:linkage to Xq probe pDP34. Genomics. 1988,3(4):299-301.
[6]Brunner HG, Bennekom AV, Lambermon EM, et al. The gene for X-linked progressive mixed deafness with perilymphatic gusher during stapes surgery (DFN3) is linked to PGK. Hum Genet,1988,80(4):337-340.
[7]De Kok YJ, Van der Maarel SM, Bitner-Glindzicz M, et al. Association between X-linked mixed deafness and mutations in the POU domain gene POU3F4. Science.1995,267(5198):685-688.
[8]Wang QJ, Li QZ, Rao SQ, et al. A novel mutation of POU3F4 causes congenital profound sensorineural hearing loss in a large Chinese family. Laryngoscope.2006,116(6):944-950.
[9]Lalwani AK, Brister JR, Fex J, et al. A new non-syndromic X-linked sensori-neural hearing impairment linked to Xp21.2. Am J Hum Genet.1994,55(4): 685-694.
[10]Pfister MH, Apaydin F, Turan O, et al. A second family with non-syndromic sensorineural hearing loss linked to Xp21.2:refinement of the DFN4 locus within DMD. Genomics.1998,53(3):377-382.
[11]Del Castillo I, Villamar M, Sarduy M, et al. A novel locus for nonsyndro-mic sensorineural deafness (DFN6) maps to chromosome Xp22. Hum Mol Genet,1996,5(9):1383-1387.
[12]赵辉,李荣华,王秋菊等.母系遗传药物性聋与非综合征性聋大家系与基因突变的研究.中华耳科学杂志.2005,3(1)：1-12.
[13]Mathis JM, Simmons DM, He X, et al. Brain 4:a novel mammalian POU domain transcription factor exhibiting restricted brain-specific expression. EMBO J.1992,11(7):2551-2561.
[14]Klemm JD, Rould MA, Aurora R, et al. Crystal structure of the Oct-1 POU domain bound to an octamer site:DNA recognition with tethered DNA-binding modules. Cell.1994,77 (1):21-32.
[15]Nussbaum RM, McInnes RR, Willard HF. THOMPSON & THOMPSON Genetics in Medicine.6th edition.英文影印本,北京大学医学出版社.2007：360-369.
[16]. Bitner-Glindzicz M, Tumpenny P, Hoglund P, et al. Further mutations in Brain 4 (POU3F4) clarify the phenotype in the X-linked deafness, DFN3. Hum Mol Genet.1995,4 (8):1467-1469.
[17]De Kok YJ, Cremers CW, Ropers HH, et al. The molecular basis of X-linked deafness type 3 (DFN3) in two sporadic cases:identification of a somatic mosaicism for a POU3F4 missense mutation. Hum Mutat.1997, 10(3):207-211.
[18]Friedman RA, Bykhovskaya Y, Tu G, et al. Molecular analysis of the POU3F4 gene in patients with clinical and radiographic evidence of X-linked mixed deafness with perilymphatic gusher. Ann Otol Rhinol Laryngol.1997,106(4):320-325.
[19]Hagiwara H, Tamagawa Y, Kitamura K, et al. A new mutation in the POU3F4 gene in a Japanese family with X-linked mixed deafness (DFN3). Laryngoscope.1998,108(10):1544-1547.
[20]Cremers FP, Cremers CW, Ropers HH. The ins and outs of X-linked deafness type 3. Adv Otorhinolaryngol.2000,56:184-195.
[21]Vore AP, Chang EH, Hoppe JE, et al. Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked non-syndromic deafness. Arch Otolaryngol Head Neck Surg.2005,131(12):1057-1063.
[22]Lee HK, Song MH, Kang M, et al. Clinical and molecular characterizations of novel POU3F4 mutations reveal that DFN3 is due to null function of POU3F4 protein. Physiol Genomics.2009,39(3):195-201.
[23]Marlin S, Moizard MP, David A, et al. Phenotype and genotype in females with POU3F4 mutations. Clin Genet.2009,76(6):558-563.
[24]Lee HK, Lee SH, Lee KY, et al. Novel POU3F4 mutations and clinical features of DFN3 patients with cochlear implants. Clin Genet.2009,75(5): 572-575.
[25]De Kok YJM, Merkx GFM, van der Maarel SM, et al. A duplication/ paracentric inversion associated with familial X-linked deafness (DFN3) suggests the presence of a regulatory element more than 400 kb upstream of the POU3F4 gene. Hum Mol Genet.1995,4(11):2145-2150.
[26]De Kok YJ, Vossenaar ER, Cremers CW, et al. Identification of a hot spot for microdeletions in patients with X-linked deafness type 3 (DFN3) 900 kb proximal to the DFN3 gene POU3F4. Hum Mol Genet.1996,5(9): 1229-1235.
[27]Marazita ML, Ploughman LM, Rawlings B, et al. Genetic epidemiological studies of early-onset deafness in the U.S. school-age population. Am J Med Genet.1993,46(5):486-491.
[28]Li Z, Li R, Chen J, et al. Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. Hum Genet.2005,117(1):9-15.
[29]Yuan H, Qian Y, Xu Y, et al. 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 nonsyn-dromic hearing loss. Am J Med Genet.2005,138A(2):133-140.
[30]Dai P, Liu X, Han D, et al. 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.2006,340(1):194-199.
[31]Wang Q, Li QZ, Han D, et al. Clinical and molecular analysis of a four-generation Chinese family with amino-glycoside-induced and non-syndromic hearing loss associated with the mitochondrial 12S rRNA C1494T mutation. Biochem Biophys Res Commun.2006,340(2):583-588.
[32]Zhu Y, Qian Y, Tang X, et al. Aminoglycoside-induced and non-syndromic hearing loss is associated with the G7444A mutation in the mitochondrial COI/tRNASer (UCN) genes in two Chinese families. Biochem Biophys Res Commun.2006,342(3):843-850.
[33]Bacino C, Prezant TR, Bu X, et al. Susceptibility mutations in the mitochondrial small ribosomal RNA gene in aminoglycoside induced deafness. Pharmacogenetics.1995,5(3):165-172.
[34]Casano RA, Johnson DF, Bykhovskaya Y, et al. Inherited susceptibility to aminoglycoside ototoxicity:genetic heterogeneity and clinical implications. Am J Otolaryngol.1999,20(3):151-156.
[35]Yoshida M, Shintani T, Hirao M, et al. Aminoglycoside-induced hearing loss in a patient with the 961 mutation in mitochondrial DNA. ORL J Otorhinolaryngol Relat Spec.2002,64(3):219-222.
[36]Kobayashi K, Oquci T, Asamura K, et al. Genetic features, clinical phenotypes, and prevalence of sensorineural hearing loss associated with the 961delT mitochondrial mutation. Auris Nasus Larynx.2005,32(2): 119-124.
[37]Bae JW, Lee KY, Choi SY, et al. Molecular analysis of mitochondrial gene mutations in Korean patients with non-syndromic hearing loss. Int J Mol Med.2008,22(2):175-180.
[1]Nussbaum RM, McInnes RR, Willard HF. THOMPSON & THOMPSON Genetics in Medicine.6th edition.英文影印本,北京大学医学出版社.2007：360-369.
[2]Su MC, Yang JJ, Su CC, et al. Identification of novel variants in the Myosin VIIA gene of patients with non-syndromic hearing loss from Taiwan. Int J Pediatr Otorhinolaryngol. Int J Pediatr Otorhinolaryngol.2009,73(6):811-5.
[3]Weil D, Blanchard S, Kaplan J, et al. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature.1995,374(6517):60-61.
[4]Hilgert N, Smith RJ, Van Camp G. Forty-six genes causing non-syndromic hearing impairment:Which ones should be analyzed in DNA diagnostics. (2009)Mutat Res.2009,681(2-3):189-96.
[5]Tantz D. Hyperriability of simple sequences as a general source for polymorphic DNA markers. Nucleic Acids Research.1989,17(16): 67632-6771.
[6]邓昊,何云贵,夏家辉.微卫星荧光标记基因组扫描.生命科学研究.2000,4(2)(专辑)：18-23.
[1]Becker MA. Phosphoribosylpyrophosphate synthetase and the regulation of phosphorribosylpyrophosphate production in human cells. Prog Nucleic Acid Res Mol Biol; 2001,69:115-148.
[2]Becker MA, Heidler SA, Bell GI, et al. Cloning of cDNAs for human phosphoribosylpyro-phosphate synthetases 1 and 2 and X chromosome localization of PRPS1 and PRPS2 genes. Genomics.1990,8 (3):555-561.
[3]Taira M, Iizasa T, Shimada H, et al. A human testis-specific mRNA for phosphoribosylpyro-phosphate synthetase that initiates from a non-AUG codon. J Biol Chem.265 (27):16491-16497.
[4]Taira M, Iizasa T, Yamada K,et al. Tissue-differential expression of two distinct genes for phosphoribosylpyrophosphate synthetase and existence of the testis-specific transcript. BiochimBiophys Acta.1989,1007(2):203-208.
[5]Becker MA, Ahmed M. Cell type-specific differential expression of human PRPP syntherase (PRPS) genes. Adv Exp Med Biol.2000,486(1):5-10.
[6]Ishizuka T, Ahmad I, Kita K, et al. The human phosphoribosylpyrophosphate synthetaseassociated protein 39 gene (PRPSAP1) is located in the chromosome region 17q24-q25. Genomics.1996,33(2):332-334.
[7]Katashima R, Iwahana H, Fujimura M, et al. Assignment of the human phosphoribosylpyrophosphate synthetase-associated protein 41 gene (PRPSAP2) to 17p11.2-p12. Genomics.1998,54(1):180-181.
[8]Li S, Lu Y, Peng B, et al. Crystal structure of human phosphoribosyl-pyrophosphate synthetase 1 reveals a novel allosteric site. J Biochem.2007, 401(1):39-47.
[9]Fox IH, Kelley WN. Human phosphoribosylpyrophosphate synthetase: distribution, purification, and properties. J Biol Chem.1971,246(18): 5739-5748.
[10]Becker MA, Kostel PJ, Meyer LJ. Human phosphoribosylpyrophosphate synthetase:comparison of purified normal and mutant enzymes. J Biol Chem.1975,250(17):6822-6830.
[11]Tatibana M, Kita K, Taira M, et al. Mammalian phosphoribosyl-pyrophosphate synthetase. Advan Enzyme Regul.1995,35:229-249.
[12]Roessler BJ, Palella TD, Heidler S, et al. Identification of distinct PRPS1 mutations in two patients with X-linked phosphoribosylpyrophosphate synthetase superactivity. Adv Exp Med Biol.1991,309B:125-128.
[13]Roessler BJ, Nosal JM, Smith PR, et al. Human X-linked phosphoribosyl-pyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. J Biol Chem.1993,268(35):26476-26481.
[14]Becker MA, Smith PR, Taylor W, et al. The genetic and functional basis of purine nucleotide feedback-resistant phosphoribosylpyrophosphate synthetase superactivity. J Clin Invest.1995,96(5):2133-2141.
[15]Garcia-Pavia P, Torres RJ, Rivero M, et al. Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. Arthritis & Rheumatism.2003,48(7):2036-2041.
[16]Kim HJ, Sohn KM, Shy ME, et al. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5). Am J Hum Genet.2007,81(3):552-558.
[17]De Brouwer APM, Williams KL, Duley JA, et al. Arts syndrome is caused by loss-of-function mutations in PRPS1. Am J Hum Genet.2007,81(3): 507-518.
[18]Liu X, Han D, Li J, et al. Loss-of-function mutations in the PRPS1 gene cause a type of non-syndromic X-linked sensorineural deafness, DFN2. Am J Hum Genet.2010,86(1):65-71.
[19]Becker MA. Phosphoribosylpyrophosphate synthetase (PRS) superactivity. Available at http://www.ncbi.nlm.gov/Books:GeneReviews. Initial Posting: September 23,2008.
[20]Zoref E, DeVries A, and Sperling A. Mutant feedback-resistant phospho-ribosylpyrophosphate synthetase associated with purine overproduction and gout. J Clin Invest.1975,56(5):1093-1099.
[21]Sperling O, Persky-Brosh S, Boer P, et al. Human erythrocyte phospho-ribosylpyrophosphate synthetase mutationally altered in regulatory properties. Biochem Med.1973,7(3):389-395.
[22]Becker MA, Puig JG, Mateos FA, et al.. Inherited superactivity of phosphoribosylpyrophosphate synthetase:association of uric acid overproduction and sensorineural deafness. Am J Med.1988,85(3): 383-390.
[23]Becker MA, Losman MJ, Wilson J, et al. Superactivity of phospho-ribosylpyrophosphate synthetase due to altered regulation by nucleotide inhibitors and inorganic phosphate. Biochim Biophys Acta.1986,882(2): 168-176.
[24]Becker MA, Losman MJ, Itkin P, et al. Gout with superactive phospho-ribosylpyrophosphate synthetase due to increased enzyme catalytic rate. J Lab Clin Med.1982,99(4):495-511.
[25]Becker MA, Losman MJ, Rosenberg AL, et al. Phosphoribosyl-pyrophosphate synthetase superactivity, A study of five patients with catalytic defects in the enzyme. Arthritis Rheum.1986,29(7):880-888.
[26]Akaoka I, Fujimori S, Kamatani N, et al. A gouty family with increased phosphoribosylpyrophosphate synthetase activity:case reports, family studies, and kinetic studies of the abnormal enzyme. J Rheumatol.1981, 8(4):563-574.
[27]Nishida Y, Akaoki I, and Horiuchi Y. Altered isoelectric property of a superactive 5-phosphoribosyl-l-pyrophosphate (PRPP) synthetase in a patient with clinical gout. Biochem Med.1981,26(3):387-394.
[28]Becker MA, Raivio KO, Bakay B, et al. Variant human phospho-ribosylpyrophosphate synthetase altered in regulatory and catalytic functions. J Clin Invest.1980,65(1):109-120.
[29]Losman MJ, Rimon D, Kim M, et al. Selective expression of phospho-ribosylpyrophosphate synthetase superactivity in human lymphoblast lines. J Clin Invest.1985,76(4):1657-1664.
[30]Becker MA. Patterns of phosphoribosylpyrophosphate and ribose-5-phosphate concentration and generation in fibroblasts from patients with gout and purine overproduction. J Clin Invest.1976,57(2):308-318.
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