线粒体tRNAIle A4317G突变可能影响12S rRNA A1555G突变相关的耳聋表型表达

doi:10.3724/SP.J.1005.2013.00752

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HEREDITAS ›› 2013, Vol. 35 ›› Issue (6): 752-760.doi: 10.3724/SP.J.1005.2013.00752

Mitochondrial tRNAIle A4317G mutation may influence the pheno-typic manifestation of deafness-associated 12S rRNA A1555G mutation

LIANG Ling-Zhi¹, WU Yue¹, YANG Ya-Ling¹, CAI Qin², XIAO Hong-Li¹, ZHENG Jing^1,3, ZHENG Bin-Jiao¹, TANG Xiao-Wen¹, ZHU Yi², LU Jian-Xin¹, GUAN Min-Xin^1,3

1. Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical College, Wenzhou 325035, China 2. Department of Otolaryngology, the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325000, China 3. College of Life Sciences, Zhejiang University, Hangzhou 310058, China

Received:2012-10-12 Revised:2012-12-25 Online:2013-06-20 Published:2013-06-25

Abstract

Abstract: Mitochondrial 12S rRNA A1555G mutation has been associated with both aminoglycoside-induced and nonsyndromic hearing loss. In this report, we performed a clinical and genetic evaluation, and mitochondrial genome analysis of one hearing-impaired Chinese family carrying the A1555G mutation. Strikingly, the penetrances of hearing loss in this family, which were 81% and 66.7%, respectively, when aminoglycoside-induced hearing loss was included or excluded. The penetrances of hearing loss in this family were significantly higher than those in other Chinese families carrying the A1555G mutation. Sequence analysis of their mitochondrial genomes revealed the presence of homoplasmic tRNAIle A4317G mutations and 38 mtDNA polymorphisms belonging to East-Asian haplogroup B4c1b2. Further analysis revealed that other mitochondrial DNA variants were not functional significantly, while the A4317G mutation is localized to a highly conserved nucleotide (conventional site 59) at tRNAIle TΨC loop of tRNAIle. The mutation may alter secondary structure and function of this tRNA, thereby leading to mitochondrial dysfunction. Allelic analysis showed that this mutation was absent in 961 hearing normal Chinese controls. Thus, the altered tRNAIle metabolism by the A4317G mutation may aggra-vate mitochondrial dysfunction associated with the A1555G mutation, and contribute to the higher penetrance of hearing loss. Therefore, the tRNAIle A4317G mutation may act as a mitochondrial modifier to influence the phenotypic manifesta-tion of the A1555G mutation.

Key words: hearing loss, mutation, mitochondrial, tRNA, phenotypic expression

LIANG Ling-Zhi WU Yue YANG Ya-Ling CAI Qin XIAO Hong-Li ZHENG Jing ZHENG Bin-Jiao TANG Xiao-Wen ZHU Yi LU Jian-Xin GUAN Min-Xin. Mitochondrial tRNAIle A4317G mutation may influence the pheno-typic manifestation of deafness-associated 12S rRNA A1555G mutation[J]. HEREDITAS, 2013, 35(6): 752-760.

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Mitochondrial tRNAIle A4317G mutation may influence the pheno-typic manifestation of deafness-associated 12S rRNA A1555G mutation

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