不同年龄段非综合征性耳聋常见基因检测及临床表型分析

doi:10.3724/SP.J.1005.2013.00352

遗传 ›› 2013, Vol. 35 ›› Issue (3): 352-358.doi: 10.3724/SP.J.1005.2013.00352

不同年龄段非综合征性耳聋常见基因检测及临床表型分析

张初琴¹, 陈波蓓¹, 陈迎迎¹ 刘学军¹, 郑静², 高金建¹, 黄赛瑜¹, 南奔宇¹, 章誉耀¹, 余啸¹, 管敏鑫^2,3

1. 温州医学院附属二院&附属育英儿童医院耳鼻喉科, 温州325027; 2. 温州医学院浙江省医学遗传学重点实验室, 温州325027; 3. 浙江大学生命科学学院, 杭州 310000

收稿日期:2012-07-05 修回日期:2012-08-07 出版日期:2013-03-20 发布日期:2013-03-25
通讯作者: 陈波蓓 E-mail:wzbobei@126.com
基金资助:
浙江省自然基金课题(编号：LY12H130001)和浙江省计生委课题(编号：200914)资助

Prevalence of common genetic mutations and clinical characteristics analysis in patients at different ages with nonsyndromic hearing im-pairment

ZHANG Chu-Qin¹, CHEN Bo-Bei¹, CHEN Ying-Ying¹, LIU XUE-Jun¹, ZHENG Jing², GAO Jin-Jian¹, HUANG Sai-Yu¹, NAN Ben-Yu¹, ZHANG Yu-Yao¹, YU Xiao¹, GUAN Min-Xin^2,3

1. Department of Otorhinolsryngology, the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical College, Wenzhou 325027, China; 2. Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325027, China; 3. College of Life Sciences, Zhejiang University, Hangzhou 310000, China

Received:2012-07-05 Revised:2012-08-07 Online:2013-03-20 Published:2013-03-25

摘要/Abstract

摘要： 为了探讨非综合征性耳聋易感基因检出率与年龄因素的相关性及其发病特点, 文章收集了2006年4月～2012年4月在温州医学院附属第二医院就诊的215名非综合征性耳聋患者, 按就诊年龄和发病年龄分别分为成人组(>18岁)及未成人组, 后者又分为婴幼儿组(0~3岁)、学龄前组(3~6岁)、学龄组(6~18岁), 提取基因组DNA, 然后进行GJB2和线粒体DNA A1555G/C1494T基因检测, 并对其阳性检出率及年龄构成比进行统计学分析。结果显示, GJB2基因突变的检出率为18.14%, 线粒体DNA A1555G/C1494T基因突变为11.16%; 就诊年龄为成人组的GJB2基因突变检出率低于未成人组(分别是5.26%, 22.36%), 线粒体DNA A1555G/C1494T基因突变则高于未成人组(分别是31.48%, 4.97%), 组间有统计学差异(χ2分别为7.108、20.852, P分别为0.008、0.000); 发病年龄为成人组及未成人组GJB2基因突变的阳性检出率分别为0%和20.10%, 组间有统计学差异(χ2=5.157, P=0.023), 而线粒体DNA A1555G/C1494T突变的阳性检出率分别为14.29%和11.34%, 组间无统计学差异(χ2= 0.160, P=0.698); GJB2基因突变的患者发病年龄多集中在l岁以内(66.67%); 线粒体DNA A1555G/ C1494T突变在各个年龄段均可发病, l岁以内仅占28.00%, 3岁以后占40.00%, 两者在年龄构成比上有统计学差异(χ2=11.035, P=0.004); 采用不同耳聋分级标准判断携带线粒体DNA A1555G/C1494T基因突变者的听力损失程度, 结果有统计学差异。这表明GJB2基因突变主要表现为先天性耳聋; 线粒体DNA A1555G/C1494T基因突变不仅可表现为先天性耳聋, 也可表现为后天进行性耳聋, 氨基糖苷类抗生素在其各个年龄段均可诱发或加重耳聋, 对其进行听力检测要重视4～8 kHz频率段; 新生儿听力筛查联合基因筛查对早期发现遗传性耳聋具有重要的意义。

关键词: 非综合征性耳聋, GJB2, 线粒体DNA, 突变, 基因诊断

Abstract: To evaluate the correlation between genetic mutations and the age in nonsyndromic hearing impairment (NSHI) and the clinical characteristics of NSHI, 215 patients with NSHI were enrolled between April 2006 and April 2012. All patients were divided into four groups according to ages of hearing loss onset and clinic presentation (0-3, 3-6, 6-18 and 18+ years). The mutations of GJB2 and mitochondria DNA (mtDNA) 1555G/C1494T were screened from peripheral blood samples in each age group. The prevalence of mutations and the age ratio were obtained. The study showed that 18.14% of all patients were found to have GJB2 mutations and 11.16% were found to have mtDNA A1555G/C1494T mutations. The prevalence of GJB2 mutation in adult group (5.26%) was lower than juvenile group who sought medical attention at 0-18 years of age (22.36%), while the prevalence of mtDNA A1555G/C1494T in adult group (31.48%) was higher than juvenile group (4.97%). Significant differences in the prevalence of GJB2 (χ2=7.108, P=0.008) and mtDNA A1555G/C1494T (χ2=20.852, P=0.000) were observed in both of two groups. The prevalence of GJB2 mutations between adult and juvenile groups according to ages of hearing loss onset was statistically significant different (0%, 20.10%, respectively, and P=0.023), while the prevalence of mtDNA A1555G/C1494T mutations was not different (14.29%, 11.34%, respectively, and P=0.698). The onset age of 66.67% of patients with GJB2 mutations was less than 1 year old, while the onset of patients with mtDNA A1555G/C1494T mutations could be found at any age group. Dif-ferent standardizations of hearing loss could also show different results. These data strongly suggest that most of GJB2 mutations are found in congenital deafness and mtDNA A1555G/C1494T mutations mainly represent acquired deafness, which can be induced or aggravated by aminoglycoside antibiotics in all age groups and should be tested mainly ranging from 4 kHz to 8 kHz. Both newborn hearing screening and genetic testing are important to find early deafness.

Key words: nonsyndromic hearing impairment, GJB2, mtDNA, mutation, genetic testing

张初琴，陈波蓓，陈迎迎，刘学军，郑静，高金建，黄赛瑜，南奔宇，章誉耀，余啸，管敏鑫. 不同年龄段非综合征性耳聋常见基因检测及临床表型分析[J]. 遗传, 2013, 35(3): 352-358.

ZHANG Chu-Qin, CHEN Bo-Bei, CHEN Ying-Ying, LIU XUE-Jun, ZHENG Jing, GAO Jin-Jian, HUANG Sai-Yu, NAN Ben-Yu, ZHANG Yu-Yao, YU Xiao, GUAN Min-Xin. Prevalence of common genetic mutations and clinical characteristics analysis in patients at different ages with nonsyndromic hearing im-pairment[J]. HEREDITAS, 2013, 35(3): 352-358.

参考文献

[1] Marcolla A, Bouchetemble P, Lerosey Y, Marie JP, Dehesdin D. Genetic deafness. Ann Otolaryngol Chir Cervicofac, 2006, 123(3): 143-147.
[2] 刘学忠, 欧阳小梅, Yan D, 袁永一, 袁慧军. 中国人群遗传性耳聋研究进展. 中华耳科学杂志, 2006, 4(2): 81-89.
[3] 戴朴, 刘新, 于飞, 朱庆文, 袁永一, 杨淑芝, 孙勍, 袁慧军, 杨伟炎, 黄德亮, 韩东一. 18个省市聋校学生非综合征性聋病分子流行病学研究(Ⅰ)-GJB2 235delC突变和线粒体DNA 12SrRNA A1555G突变筛查报告. 中华耳科学杂志, 2006, 4(1): 1-5.
[4] 王秋菊, 顾瑞. 关于非综合征型遗传性听损伤家系遗传学及听力学描述术语建议案. 中华耳科学杂志, 2003, 1(4): 46-47, 67.
[5] 李征玥, 程静, 卢宇, 张旭, 金占国, 贾婧杰, 袁慧军. 进行性非综合征型聋家系临床表型及遗传学分析. 听力学及言语疾病杂志, 2012, 20(3): 201-205.
[6] Li R, Greinwald JH Jr, Yang L, Choo DI, Wenstrup RJ, Guan MX. Molecular analysis of the mitochondrial 12S rRNA and tRNASer(UCN) genes in paediatric subjects with non-syndromic hearing loss. J Med Genet, 2004, 41(8): 615-620.
[7] Li R, Xing G, Yan M, Cao X, Liu XZ, Bu X, Guan MX. Cosegregation of C-insertion at position 961 with the A1555G mutation of the mitochondrial 12S rRNA gene in a large Chinese family with maternally inherited hearing loss. Am J Med Genet A, 2004, 124A(2): 113-117.
[8] Chen BB, Sun DM, Yang L, Zhang CQ, Yang A, 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, tRNA(Cys) T5802C, and tRNA(Thr) G15927A variants may have a modifying role in the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation in three Han Chinese pedigrees. Am J Med Genet A, 2008, 146A(10): 1248-1258.
[9] Andrews RM, Kubacka I, Chinnery PF, Lightowlers RN, Turnbull DM, Howell N. Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA. Nat Genet, 1999, 23(2): 147.
[10] 王国建, 袁永一, 韩冰, 黄莎莎, 康东洋, 张昕, 董敏, 韩东一, 戴朴. 不同年龄的重度耳聋患者常见耳聋基因突变的阳性率分析. 中华耳科学杂志, 2010, 8(4): 392-396.
[11] Guan MX. Mitochondrial 12s rRNA mutations associated with aminoglycoside ototoxicity. Mitochondrion, 2011, 11(2): 237-245.
[12] 胡书君, 历建强, 张鹏, 兰兰, 郑锦, 李娜, 宋杰, 王大勇, 田红霞, 丁海娜, 王嵩川, 王秋菊. 新生儿听力与聋病易感基因联合筛查的临床研究. 听力学及言语疾病杂志, 2010, 18(3): 222-224.
[13] 张初琴, 陈波蓓, 黄加云, 孙东梅, 陈迎迎, 项松洁, 管敏鑫. 人工耳蜗植入聋儿术前基因检测及家系分析. 遗传, 2008, 30(11): 1406-1410.
[14] Todt I, Hennies HC, Basta D, Ernst A. Vestibular dysfunction of patients with mutations of Connexin 26. Neuroreport, 2005, 16(11): 1179-1181.
[15] Ohtsuka A, Yuge I, Kimura S, Namba A, Abe S, Van Laer L, Van Camp G, Usami S. GJB2 deafness gene shows a specific spectrum of mutations in Japan, including a frequent founder mutation. Hum Genet, 2003, 112(4): 329-333.
[16] Lefebvre PP, Van De Water TR. Connexins, hearing and deafness: clinical aspects of mutations in the connexin 26 gene. Brain Res Brain Res Rev, 2000, 32(1): 159-162.
[17] Hobertson NG, Lu L, Heller S, Merchant SN, Eavey RD, McKenna M, Nadol JB Jr, Miyamoto RT, Linthicum FH Jr, Lubianca Neto JF, Hudspeth AJ, Seidman CE, Morton CC, Seidman JG. Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction. Nat Genet, 1998, 20(3): 299-303.
[18] 姜鸿, 陈晓巍. 耳聋基因诊断. 协和医学杂志, 2012, 3(2): 134-137.
[19] Qian YP, Guan MX. Interaction of aminoglycosides with human mitochondrial 12S rRNA carrying the deafness- associated mutation. Antimicrob Agents Chemo-ther, 2009, 53(11): 4612-4618.
[20] 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. 遗传, 2012, 34(6): 695-704.
[21] 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.
[22] 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.
[23] 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.
[24] Lu J, Li Z, Zhu Y, Yang A, Li R, Zheng J, Cai Q, Peng G, Zheng W, Tang X, Chen B, Chen J, Liao Z, Yang L, Li Y, You J, Ding Y, Yu H, Wang J, Sun D, Zhao J, Xue L, Wang J, Guan MX. Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss. Mitochondrion, 2010, 10(4): 380-390.
[25] 李琦, 方如平, 王国建, 刘芳, 戴朴. GJB2 235 delC 单杂合突变携带者的纯音测听评估. 中华耳鼻咽喉头颈外科杂志, 2011, 46(7): 543-546.

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不同年龄段非综合征性耳聋常见基因检测及临床表型分析

Prevalence of common genetic mutations and clinical characteristics analysis in patients at different ages with nonsyndromic hearing im-pairment

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