浙江省非综合征型耳聋患者12S rRNA突变频谱分析

doi:10.3724/SP.J.1005.2012.00695

遗传 ›› 2012, Vol. 34 ›› Issue (6): 695-704.doi: 10.3724/SP.J.1005.2012.00695

浙江省非综合征型耳聋患者12S rRNA突变频谱分析

郑斌娇¹, 彭光华², 陈波蓓³, 方芳¹, 郑静¹, 伍越¹, 梁玲芝¹, 南奔宇³, 唐霄雯¹, 朱翌⁴, 吕建新¹, 管敏鑫^{1, 5}

1. 温州医学院, Attardi线粒体生物医学研究院和浙江省医学遗传学重点实验室, 温州 325035 2. 余姚市人民医院耳鼻咽喉科, 宁波 315400 3. 温州医学院附属第二医院附属育英儿童医院耳鼻喉科, 温州 325027 4. 温州医学院附属第一医院耳鼻喉科, 温州 325027 5. 浙江大学生命科学学院, 杭州 310058

收稿日期:2011-10-19 修回日期:2011-11-28 出版日期:2012-06-20 发布日期:2012-06-25
通讯作者: 管敏鑫 E-mail:gminxin88@gmail.com
基金资助:
国家重点基础研究发展规划(973计划)项目(编号：2004CCA02200), 国家自然科学基金项目(编号：81070794), 浙江省重大科技专项社会发展项目(编号：2007C13021), 浙江省卫生厅项目(编号：2009A135), 浙江省研究生创新科研项目(编号：YK2010084)和温州市科技局项目(编号：Y20080122)资助

Spectrum and frequency of mitochondrial 12S rRNA variants in the Chinese subjects with nonsynrdomic hearing loss in Zhejiang Province

ZHENG Bin-Jiao¹, PENG Guang-Hua², CHEN Bo-Bei³, FANG Fang¹, ZHENG Jing¹, WU Yue¹, LIANG Ling-Zhi¹, NAN Ben-Yu³, TANG Xiao-Wen¹, ZHU Yi⁴, LU Jian-Xin¹, GUAN Min-Xin^1,5

1. Attardi Institute of Mitochondrial Biomedicine and Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China 2. Department of Otolaryngology, Yuyao People’s Hospital, Ningbo 315400, China 3. Department of Otolaryngology, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical College, Wenzhou 325027, China 4. Department of Otolaryngology, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, China 5. College of Life Sciences, Zhejiang University, Hangzhou 310058, China

Received:2011-10-19 Revised:2011-11-28 Online:2012-06-20 Published:2012-06-25

摘要/Abstract

摘要： 线粒体DNA (Mitochondrial DNA , mtDNA)突变是引起耳聋的重要原因之一。尤其是12S rRNA基因是药物性耳聋与非综合征型耳聋相关的突变热点区域。文章收集了浙江省各地区非综合征型及药物性耳聋患者标本318例, 对其进行临床和分子遗传学评估。12S rRNA基因突变分析发现34个变异位点, 已知的1555A>G、1494C>T和1095T>C突变分别占9.1%、0.6%和1.25%。结构和种系发生分析显示, 839A>G和1452T>C突变位于12S rRNA基因的高度保守区域且未在449例正常对照组中发现, 可能增加了耳毒性药物的敏感性。其他变异位点为多态性位点。文章数据支持了12S rRNA基因是耳毒性药物的作用靶点之一这一理论, 为预测个体耳毒性的发生风险, 提高氨基糖甙类药物治疗安全性提供了有价值的信息, 以期降低耳聋的发生。

关键词: 线粒体12S rRNA基因, 非综合征型耳聋, 氨基糖甙类药物, 突变频谱听力损失

Abstract: Mitochondrial DNA (mtDNA) mutations are one of the important causes of deafness. In particular, the 12S rRNA gene is the hot spots for mutations associated with both aminoglycoside ototoxicity and nonsyndromic deafness. In this report, a total of 318 Chinese pediatric hearing-impaired subjects were recruited from otology clinics in the Zhejiang Province, China. These subjects underwent clinical, genetic evaluation and molecular analysis of 12S rRNA gene. Mutational analysis identified 34 variants in the 12S rRNA gene in this cohort. The incidences of the known deafness-associated 1555A>G, 1494C>T and 1095T>C mutations were 9.1%, 0.6% and 1.25% in this cohort, respectively. Other mtDNA variants were evaluated by structural and phylogenetic analysis. Of these, the 839A>G and 1452T>C variants could confer increased sensitivity to aminoglycosides or nonsyndromic deafness as they were not present in 449 Chinese controls and localized at highly conserved nucleotides of the 12S rRNA. However, other variants appeared to be polymorphisms. These data further support the idea that mitochondrial 12S rRNA is one of major targets for aminoglycoside ototoxicity. These data have been providing valuable information to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.

Key words: hearing loss, mitochondrial 12S rRNA gene, non-syndromic deafness, aminoglycoside antibiotics, mutation spectrum

郑斌娇，彭光华，陈波蓓，方芳，郑静，伍越，梁玲芝，南奔宇，唐霄雯，朱翌，吕建新，管敏鑫. 浙江省非综合征型耳聋患者12S rRNA突变频谱分析[J]. 遗传, 2012, 34(6): 695-704.

ZHENG Bin-Jiao, PENG Guang-Hua, CHEN Bo-Bei, FANG Fang, ZHENG Jing, WU Yue, LIANG Ling-Zhi, NAN Ben-Yu, TANG Xiao-Wen, ZHU Yi, LU Jian-Xin, GUAN Min-Xin. Spectrum and frequency of mitochondrial 12S rRNA variants in the Chinese subjects with nonsynrdomic hearing loss in Zhejiang Province[J]. HEREDITAS, 2012, 34(6): 695-704.

参考文献

[1] Morton CC. Genetics, genomics and gene discovery in the auditory system. Hum Mol Genet, 2002, 11(10): 1229-1240.
[2] 管敏鑫, 赵立东. 与氨基糖甙类抗生素耳毒性相关的线粒体12S rRNA突变的流行病学特征. 中华耳科学杂志, 2006, 4(2): 98-105.
[3] Guan MX. Mitochondrial 12S rRNA mutations associated with aminoglycoside ototoxicity. Mitochondrion, 2011, 11(2): 237-245.
[4] Xing G, Chen Z, Cao X. Mitochondrial rRNA and tRNA and hearing function. Cell Res, 2007, 17(3): 227-239.
[5] Fischel-Ghodsian N. Genetic factors in aminoglycoside toxicity. Pharmacogenomics, 2005, 6(1): 27-36.
[6] 杨爱芬, 郑静, 吕建新, 管敏鑫. 修饰因子对线粒体DNA突变致聋的影响. 中华医学遗传学杂志, 2010, 28(2): 165-171.
[7] Hutchin T, Haworth I, Higashi K, Fischel-Ghodsian N, Stoneking M, Saha N, Arnos C, Cortopassi G. A molecular basis for human hypersensitivity of aminoglyscoside antibiotics. Nuclear Acids Res, 1993, 21(18): 4174-4179.
[8] Prezant TR, Agapian JV, Bohlman MC, Bu XD, Öztas S, Qiu WQ, Arnos KS, Cortopassi GA, Jaber L, Rotter JI, Shohat M, Fischel-Ghodsian N. Mitochondrial ribosomal RNA mutation associated with both antibiotic-induced and non-syndromic deafness. Nature Genet, 1993, 4: 289-294.
[9] Estivill X, Govea N, Barceló E, Badenas C, Romero E, Moral L, Scozzari R, D’Urbano L, Zeviani M, Torroni A. Familial progressive sensorineural deafness is mainly due to the mtDNA A1555G mutation and is enhanced by treatment with aminoglycosides. Am J Hum Genet, 1998, 62(1): 27-35.
[10] Matthijs G, Claes S, Longo-Bbenza B, Cassiman JJ. Non- syndromic deafness associated with a mutation and a polymorphism in the mitochondrial 12S ribosomal RNA gene in a large Zairean pedigree. Eur J Hum Genet, 1996, 4(1): 46-51.
[11] Lévêque M, Marlin S, Jonard L, Procaccio V, Reynier P, Amati-Bonneau P, Baulande S, Pierron D, Lacombe D, Duriez F, Francannet C, Mom T, Journel H, Catros H, Drouin-Garraud V, Obstoy MF, Dollfus H, Eliot MM, Faivre L, Duvillard C, Couderc R, Garabedian EN, Petit C, Feldmann D, Denoyelle F. Whole mitochondrial genome screening in maternally inherited non-syndromic hearing impairment using a microarray resequencing mitochon-drial DNA chip. Eur J Hum Genet, 2007, 15(11): 1145-1155.
[12] 张婷, 陈波蓓, 郑静, 龚莎莎, 张初琴, 吕建新, 管敏鑫. 五个母系遗传非综合征性耳聋和药物性耳聋的中国汉族家系. 中华医学遗传学, 2011, 28(4): 367-373.
[13] Chen BB, Sun DM, Yang L, Zhang CQ, Yang AF, Zhu Y, Zhao JY, Chen YY, Guan MQ, Wang XJ, Li RH, Tang XW, Wang JD, Tao ZH, Lu JX, Guan MX. Mitochondrial ND5 T12338C, tRNACys T5802C, and tRNAThr G15927A variants may have a modifying role in the phe-notypic manifestation of deafness-associated 12S rRNA A1555G mutation in three Han Chinese pedigrees. Am J Med Genet, 2008, 146A(10): 1248-1258.
[14] Lu JX, Qian YP, Li ZY, Yang AF, Zhu Y, Li RH, Yang L, Tang XW, Chen BB, Ding Y, Li YY, You JY, Zheng J, Tao ZH, Zhao FX, Wang JD, Sun DM, Zhao JY, Meng YZ, Guan MX. Mitochondrial haplotypes may modulate the phenotypic manifestation of the deafness-associated 12S rRNA 1555A > G mutation. Mitochondrion, 2010, 10(1): 69-81.
[15] Zhao H, Li RH, Wang QJ, Yan QF, Deng JH, Han DY, Bai YD, Young WY, Guan MX. Maternally inherited amino-glycoside-induced and nonsyndromic deafness is associated with the novel C1494T mutation in the mitochondrial 12S rRNA gene in a large Chinese family. Am J Hum Genet, 2004, 74(1): 139-152.
[16] Rodriguez-Ballesteros M, Olarte M, Aguirre LA, Galán F, Galán R, Vallejo LA, Navas C, Villamar M, Mo-reno-Pelayo MA, Moreno F, del Castillo I. Molecular and clinical characterisation of three Spanish families with maternally inherited non-syndromic hearing loss caused by the 1494C→T mutation in the mitochondrial 12S rRNA gene. J Med Genet, 2006, 43(11): e54.
[17] Chen J, Yang L, Yang A, Zhu Y, Zhao J, Sun D, Tao Z, Tang X, Wang J, Wang X, Tsushima A, Lan J, Li W, Wu F, Yuan Q, Ji J, Feng J, Wu C, Liao Z, Li Z, Greinwa

编辑推荐

Metrics

www.chinagene.cn
备案号：京ICP备09063187号-4
总访问:,今日访问:,当前在线:

浙江省非综合征型耳聋患者12S rRNA突变频谱分析

Spectrum and frequency of mitochondrial 12S rRNA variants in the Chinese subjects with nonsynrdomic hearing loss in Zhejiang Province

PDF (PC)

可视化

被引次数

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 2

编辑推荐

Metrics

[1]	彭光华，郑斌娇，方芳，伍越，梁玲芝，郑静，南奔宇，余啸，唐霄雯，朱翌，吕建新，陈波蓓，管敏鑫. 25个携带线粒体12S rRNA A1555G突变的中国汉族非综合征型耳聋家系[J]. 遗传, 2013, 35(1): 62-72.
[2]	舒安利，聂玉正. 近亲结婚所致一遗传性非综合征型耳聋家系的调查[J]. 遗传, 2005, 27(4): 553-556.