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线粒体tRNAThr G15927A突变可能影响耳聋相关的12S rRNA A1555G突变的表型表达
引用本文:唐霄雯,李智渊,吕建新,朱翌,李荣华,王金丹,管敏鑫.线粒体tRNAThr G15927A突变可能影响耳聋相关的12S rRNA A1555G突变的表型表达[J].遗传,2008,30(10):1287-1294.
作者姓名:唐霄雯  李智渊  吕建新  朱翌  李荣华  王金丹  管敏鑫
作者单位:1. 温州医学院浙江省医学遗传学重点实验室,温州,325035
2. 温州医学院附属第一医院耳鼻喉科,温州,325000
3. Division and Program in Human Genetic and Center for Hearing and Deafness Research,Cincinnati Children's Hospital Medical Center,Cininnati OH45229,USA
4. 温州医学院浙江省医学遗传学重点实验室,温州,325035;Division and Program in Human Genetic and Center for Hearing and Deafness Research,Cincinnati Children's Hospital Medical Center,Cininnati OH45229,USA
基金项目:国家重点基础研究发展规划(973计划)前期研究专项,浙江省卫生厅资助项目,浙江省科技厅钱江人才优先资助项目,浙江省温州市科技局资助项目
摘    要:摘要: 对1个中国汉族耳聋家系进行了临床和分子遗传学特征分析。家系中听力下降的母系成员表现为程度不等、听力图形态不同的听力损害, 但同为双侧对称的感觉神经性耳聋。该家系耳聋外显率很高, 包括药物致聋的耳聋外显率为75%, 而非药物致聋的外显率为41.7%。对母系成员进行线粒体DNA(mtDNA)全序列扩增分析, 发现了耳聋相关12S rRNA A1555G同质性突变位点和多态性位点, 属于东亚人群B5b单体型。在这些变异位点中, mtDNA 15927位点的G-A碱基变化破坏tRNAThr反密码子结构上十分保守的C-G碱基对, 这可能加重由A1555G突变造成的线粒体功能缺陷。这表明tRNAThrG15927A突变可能增强携带12S rRNA A1555G的中国汉族耳聋家系的外显率和表现度。

关 键 词:耳聋  线粒体DNA(mtDNA)  突变  单体型  tRNA
收稿时间:2008-03-03
修稿时间:2008-07-04

Mitochondrial tRNAThr G15927A mutation may influence the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation
TANG Xiao-Wen,LI Zhi-Yuan,LU Jian-Xin,ZHU Yi,LI Rong-Hun,WANG Jin-Dan,GUAN Min-Xin.Mitochondrial tRNAThr G15927A mutation may influence the phenotypic manifestation of deafness-associated 12S rRNA A1555G mutation[J].Hereditas,2008,30(10):1287-1294.
Authors:TANG Xiao-Wen  LI Zhi-Yuan  LU Jian-Xin  ZHU Yi  LI Rong-Hun  WANG Jin-Dan  GUAN Min-Xin
Institution:1. Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China;
2. Department of Otolaryngology, the First Affiliated Hospital, Wenzhou Medical College, Wenzhou 325000, China;
3. Division and Program in Human Genetic and Center for Hearing and Deafness Research, Cincinnati Children’s Hospital Medical Cen-ter, Cininnati OH45229, USA
Abstract:Abstract: We report here the clinical and genetic evaluations as well as mutational analysis of mitochondrial DNA (mtDNA) in a four-generation Chinese Han family with aminoglycoside-induced and nonsyndromic hearing loss. Strikingly, this fam-ily exhibited a high penetrance and expressivity of hearing loss. The penetrances of hearing loss in this family were 75% and 41.7% respectively, when aminoglycoside-induced deafness was included or was excluded. The severity of hearing loss in matrilineal relatives varied from profound hearing loss to normal hearing. Mutational analysis of mtDNA identified the homoplasmic A1555G mutation and a distinct set of mtDNA variants belonging to the Asian haplogroup B5b. Of these, the G15927A mutation absent in 156 Chinese controls is localized at the anticodon-stem of tRNAThr at conventional position 42. The guanine at this position (G42) of tRNAThr is highly conserved from bacteria to human mitochondria. Thus, it is antici-pated that the G15927A disrupted the highly conserved C-G base-pairing at the anticodon-stem of tRNAThr. The alteration of structure of this tRNA likely leads to a failure in tRNA metabolism, thereby worsens the mitochondrial dysfunction asso-ciated with the A1555G mutation. Thus, the G15927A mutation has a potential modifying role in increasing the penetrance and expressivity of hearing loss associated with the deafness-associated 12S rRNA A1555G mutation in this Chinese pedigree.
Keywords:tRNA
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