线粒体DNA G7444A突变可能影响A1555G突变的表型表达

doi:10.3724/SP.J.1005.2008.00728

遗传 ›› 2008, Vol. 30 ›› Issue (6): 728-734.doi: 10.3724/SP.J.1005.2008.00728

线粒体DNA G7444A突变可能影响A1555G突变的表型表达

杨爱芬¹; 朱翌^{1, 2}; 吕建新¹; 杨丽³; 赵建越¹; 孙冬梅¹; 管敏鑫^{1, 3}

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, 温州 325000;
3. Division of Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children’s Hospital Medical Center, Cin-cinnati, Ohio 45229, USA

收稿日期:2008-01-06 修回日期:2008-02-29 出版日期:2008-06-10 发布日期:2008-06-10
通讯作者: 管敏鑫

Mitochondrial DNA G7444A mutation may influence the pheno-typic manifestation of the deafness-associated 12S rRNA A1555G mutation

YANG Ai-Fen¹; ZHU Yi^{1, 2}; LU Jian-Xin¹; YANG Li³; ZHAO Jian-Yue¹; SUN Dong-Mei¹; GUAN Min-Xin^{1, 3}

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 of Human Genetics and Center for Hearing and Deafness Research, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229, USA

Received:2008-01-06 Revised:2008-02-29 Online:2008-06-10 Published:2008-06-10
Contact: GUAN Min-Xin

摘要/Abstract

摘要：

线粒体12S rRNA和tRNASer(UCN) 基因是导致非综合征型听力损失的两个突变热点区域。作者收集了1个母系遗传感音神经性聋家系, 该家系同时携带线粒体DNA (mtDNA) A1555G和G7444A突变。临床资料分析表明, 该家系包括药物致聋的耳聋外显率(所有耳聋患者/所有母系成员)为58%, 而非药物致聋的耳聋外显率(非药物性聋患者/所有母系成员)为25%, 明显高于其他携带A1555G突变的耳聋家系。先证者的线粒体全序列分析表明, 该线粒体基因组共有28个多态位点, 属于东亚人群B4c1单体型。在这些多态位点中, 除A1555G和G7444A突变外, 未发现其他有功能意义的突变。这表明mtDNA G7444A突变可能加重由A1555G突变造成的线粒体功能缺失, 从而增加耳聋的外显率。

关键词: 氨基糖甙类抗生素, 非综合征耳聋, 线粒体DNA, 基因突变

Abstract:

Mitochondrial 12S rRNA and tRNASer(UCN) genes are the hot spots for mutations associated with hearing loss. We reported here the clinical, genetic and molecular analysis of a Chinese pedigree with maternally inherited sensorineural hearing loss. Molecular analysis showed that the pedigree carried both mitochondrial DNA (mtDNA) A1555G and G7444A mutations. The penetrance of hearing loss in this pedigree was 58% when aminoglycoside-induced hearing loss was included. When the effect of aminoglycosides was excluded, the penetrance of hearing loss in this pedigree was 25%. The penetrance of hearing loss was significantly higher than other families carrying only A1555G mutation. Sequence analysis of the complete mitochondrial genome in the proband showed that there were 28 mtDNA polymorphisms belonging to East-Asian haplogroup B4c1. In addition to the deafness-associated A1555G and G7444A mutations, there were no other functionally significant variants found in this family. This indicated that mtDNA G7444A mutation may aggravate mitochondrial dysfunction associated with the A1555G mutation. Therefore, the coexistence of both mtDNA mutations may contribute to high penetrance of hearing loss.

杨爱芬，朱翌，吕建新，杨丽，赵建越，孙冬梅，管敏鑫. 线粒体DNA G7444A突变可能影响A1555G突变的表型表达[J]. 遗传, 2008, 30(6): 728-734.

YANG Ai-Fen, ZHU Yi, LU Jian-Xin, YANG Li, ZHAO Jian-Yue, SUN Dong-Mei, GUAN Min-Xin. Mitochondrial DNA G7444A mutation may influence the pheno-typic manifestation of the deafness-associated 12S rRNA A1555G mutation[J]. HEREDITAS, 2008, 30(6): 728-734.

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线粒体DNA G7444A突变可能影响A1555G突变的表型表达

Mitochondrial DNA G7444A mutation may influence the pheno-typic manifestation of the deafness-associated 12S rRNA A1555G mutation

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