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The Study of Mitochondrial Function in A Nonsyndromic Hearing Loss Family Carrying Mitochondria tRNAThr 15910C>T and 12S rRNA 1555A>G Mutations
Yao Juan1, Lin Zhi1, Wang Hui1, Gao Yinglong3, Fan Wenlu1, Wang Heng1, Jiang Feng1,Xue Ling1, Tang Xiaowen2, Zheng Binjiao1, Guan Minxin1,3*
1Attardi Institute of Mitochondrial Biomedicine, Wenzhou Medical University, Wenzhou 325035, China;
2Renji College, Wenzhou Medical University, Wenzhou 325035, China;
3Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China
2Renji College, Wenzhou Medical University, Wenzhou 325035, China;
3Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China
Abstract: In this study， we investigated the mitochondrial function of 12S rRNA 1555A>G and mitochondria tRNAThr 15910C>T mutations in a nonsyndromic hearing loss (NSHL) family. We established three groups of lymphoblastoid cell lines in this study， including the double mutations group， the single mutation group and the controls， which all belong to the Eastern Asian haplogroup R. The double mutations group are 3 subjects carried both m.1555A>G and m.15910C>T. The single mutation group are 3 subjects carried m.1555A>G mutation only. The controls are 3 subjects with normal auditory sense. To analyze the clinical data of the family， the penetrance of deafness is 37.5% or 25.0% which contains or excludes the family members who have used AmAn drugs; while the penetrance of deafness is 12.8% or 6.1% which contains or excludes the family members who have used AmAn drugs in the 14 reported deafness families with m.1555A>G mutation. Compared with controls， the ROS level in the double-mutations group has been raised 19.08% (P=0.005 4) and the single-mutation group only raised 9.05% (P=0.003 7). Compared with controls， the mitochondrial membrane potential decreased 47.78% (P=0.006 3) and 35.39% (P=0.024 5) in the double-mutations group and the single-mutation group， respectively. It showed that 8.26% (P=0.721 1) and 19.48% (P=0.004 9) decrease in the activity of respiratory chain complex II while 32.75% (P=0.033 5) and 27.44% (P=0.180 5) decrease in the activity of respiratory chain complex IV in the double-mutations group and the single-mutation group compared with controls. These results showed that m.1555A>G and m.15910C>T led to mitochondrial dysfunction， included ROS raise up， mitochondrial membrane potential and the activity of respiratory chain complex IV decreased. Thus， m.15910C>T worsens the mitochondrial function associated with m.1555A>G， and is probably a secondary mutation of m.1555A>G caused deafness.
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