线粒体tRNAAsp A7551G突变可能是耳聋相关的线粒体基因新突变

doi:10.3760/cma.j.issn.1673-0860.2013.12.003

科研成果详情

题名	线粒体tRNAAsp A7551G突变可能是耳聋相关的线粒体基因新突变
其他题名	Hearing loss may be associated with the novel mitochondrial tRNAAsp A7551G mutation in a Chinese family
作者	伍越 1; 梁玲芝 1; 肖红利1; 阳娅玲1; 余啸 2; 郑静 3; 方芳 1; 郑斌娇 1; 唐霄雯1; 金龙金1; 管敏鑫1
发表日期	2013
发表期刊	中华耳鼻咽喉头颈外科杂志影响因子和分区
语种	中文
原始文献类型	期刊论文
关键词	听觉丧失 DNA，线粒体 RNA，转移，天冬氨酸连接蛋白类突变
其他关键词	Hearing loss ; DNA,mitochondrial ; RNA,transfer,Asp ; Connexins ; Mutation
摘要	目的通过对携带线粒体tRNA~(Asp)A7551G突变的母系遗传非综合征型耳聋家系进行临床和分子遗传学特征分析，探讨线粒体tRNA~(Asp)基因突变对非综合征型耳聋的影响。方法收集1个携带线粒体tRNA~(Asp) A7551G突变的非综合征型耳聋家系，对先证者及其家系成员进行听力学检查、线粒体基因组全序列分析和GJB2基因突变检测等。结果家系內共6人患病，母系成员占4人。先证者线粒体全基因组分析表明，该线粒体基因组含28个多态位点，属于东亚人群A4单体型。其中除A7551G同质性突变外，无其他有功能意义的多态位点。A7551G突变位于线粒体tRNA~(Asp)反密码子环的反密码子旁高度保守区的第37位，保守性指数为100%且未在正常对照中发现。GJB2基因突变分析发现先证者及家系成员携带有与耳聋相关的235delC、299delAT突变位点。家系内母系成员在发病年龄、听力损失程度和听力曲线上存在较大差异。结论线粒体tRNAAsp A7551G突变可能通过改变对tRNA二级结构的修饰作用，影响tRNA结构的稳定性，最终导致线粒体功能异常，引起耳. 聋表型，该突变可能是与耳聋相关的线粒体基因新突变。
其他摘要	Objective We reported here the clinical and genetic evaluations as well as mutational analysis of mitochondrial DNA ( mtDNA) in a Chinese family with maternally transmitted non-syndromic hearing loss and investigated the influence of the mitochondrial tRNAAsp A7551G mutation to the phenotypic manifestation of the deafness. Methods One Chinese Han pedigrees of maternally transmitted nonsyndromic hearing loss were collected. The proband and family members underwent clinical, genetic, and molecular evaluations, such as audiological examinations,mutational analysis of mitochondrial genome and mutational analysis of GJB2 gene. Results Six people of this pedigree suffered from hearing loss, including four matrilineal members, and others did not have significant clinical abnormalities. Sequence analysis of the complete mitochondrial genome in the proband showed that there were 28 mtDNA polymorphisms belonging to East -Asian haplogroup A4. In addition to the A7551G homogeneity mutation, there were no other functionally significant variants found in this family. The A7551G mutation located immediately at the three prime end to the anticodon, corresponding with the conventional position 37 of tRNAAsp,and its' CI value was 100% compared with other 15 primate species. The A7551G mutation was absent in other Chinese controls. The mutations on GJB2 were detected by direct sequence analysis, GJB2 235delC and 299del AT which was associated with hearing loss were found in the geneomic DNA of the proband and some matrilineal members. Clinical evaluation showed a variable phenotype of severity, age-at-onset and audiometric configuration of hearing loss in the matrilineal relatives in these families. Conclusions The A7551G mutation may modify the secondary structure of the tRNA,and affect the stabilization of tRNAAsp,produce non-normal functional tRNAAsp ultimately. And it may cause the phenotypic manifestation of the deafness that associated with A7551G mutation. Therefore, the mitochondrial tRNAAsp A7551G mutation may be a new mitochondrial mutation for hearing loss.
资助项目	国家自然科学基金 ; 国家自然科学基金国家杰出青年科学基金 ; 浙江省自然科学基金 ; 浙江省卫生厅医药卫生科学研究基金 ; 温州市瓯海区科技计划项目
ISSN	1673-0860
卷号	48 期号:12 页码:978-984
DOI	10.3760/cma.j.issn.1673-0860.2013.12.003
页数	7
收录类别	CSCD ; 万方 ; ISTIC ; PKU ; 北大核心
学科领域	医药、卫生
URL	查看原文
CSCD记录号	CSCD:5007500
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/99686
专题	第二临床医学院、附属第二医院、育英儿童医院检验医学院（生命科学学院、生物学实验教学中心）附属第二医院附属第二医院_耳鼻咽喉科检验医学院（生命科学学院、生物学实验教学中心）_Attardei线粒体研究院
作者单位	1.温州医科大学Attardi线粒体生物医学研究院, 325035 ; 2.温州医科大学附属第二医院附属育英儿童医院耳鼻咽喉科 ; 3.浙江大学生命科学学院
第一作者单位	Attardei线粒体研究院
第一作者的第一单位	Attardei线粒体研究院
推荐引用方式 GB/T 7714	伍越,梁玲芝,肖红利,等. 线粒体tRNAAsp A7551G突变可能是耳聋相关的线粒体基因新突变[J]. 中华耳鼻咽喉头颈外科杂志,2013,48(12):978-984.
APA	伍越., 梁玲芝., 肖红利., 阳娅玲., 余啸., ... & 管敏鑫. (2013). 线粒体tRNAAsp A7551G突变可能是耳聋相关的线粒体基因新突变. 中华耳鼻咽喉头颈外科杂志, 48(12), 978-984.
MLA	伍越,et al."线粒体tRNAAsp A7551G突变可能是耳聋相关的线粒体基因新突变".中华耳鼻咽喉头颈外科杂志 48.12(2013):978-984.