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。
Mitochondrial 12S rRNA and tRNA^ser（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 carded both mitochondrial DNA （mtDNA） A 1555G 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 B4cl. 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.
出处
《遗传》
CAS
CSCD
北大核心
2008年第6期728-734,共7页
Hereditas（Beijing)
基金
国家“973”重大基础研究前期研究专项(编号:2004CCA02200)
浙江省卫生厅课题(编号:2006A100)
浙江省科技厅钱江人才优先资助项目(编号:2007G50G2090026)
浙江省重大科技专项社会发展项目(编号:2007C13021)资助~~
