Complete mitochondrial DNA sequence analysis in two southern Chinese pedigrees with Leber hereditary optic neuropathy revealed secondary mutations along with the primary mutation

作     者：Lei Shu Yong-Ming Zhang Xiao-Xiao Huang Chun-Yue Chen Xian-Ning Zhang 

作者机构：Hangzhou Red Cross Hospital Hangzhou 310003 Zhejiang Province China Department of Biochemistry and Genetics National Education Base for Basic Medical Sciences Institute of Cell Biology School of Medicine Zhejiang University Hangzhou 310058 Zhejiang Province China Department of Ophthalmology Xiangshan First People's Hospital Xiangshan County 315700 Zhejiang Province China Hangzhou No. 6 Hospital Hangzhou 310014 Zhejiang Province China 

出 版 物：《International Journal of Ophthalmology(English edition)》 (国际眼科杂志(英文版))

年 卷 期：2012年第5卷第1期

页      面：28-31页

核心收录：

学科分类：1002[医学-临床医学] 100212[医学-眼科学] 10[医学] 

基　　金：Supported by the National Natural Science Foundation of China(No.J0710043) 

主　　题：Leber hereditary optic neuropathy mitochondrial DNA mutation mitochondrial respiratory complex I 

摘      要：AIM: To investigate mitochondrial factors associated with Leber hereditary optic neuropathy (LHON) through complete sequencing and analysis of the mitochondrial genome of Chinese patients with this disease. METHODS: Two unrelated southern Chinese families with LHON and 10 matched healthy controls were recruited, and their entire mitochondrial DNA (mtDNA) was amplified and sequenced with the universal M13 primer. Then DNA sequence analysis and variation identification were performed by DNAssist and Chromas 2 software and compared with authoritative databases such as Mitomap. RESULTS: Mutational analysis of mtDNA in these two Chinese pedigrees revealed one common LHON-associated mutation, G11778A (Arg - His), in the MT-ND4 gene. In addition, there were two secondary mutations in Pedigree 1: C34971 (Ala - Val), and C3571T (Leu - Phe) in the MT-ND1 gene, which have not been reported; and two secondary mutations occurred in Pedigree 2: A10398G (Thr - Ala) in the MT-ND3 gene, and T14502C (Ile - Val) in the MT-ND6 gene. Three polymorphisms, A73G, G94A and A263G in the mtDNA control region, were also found. CONCLUSION: Our study confirmed that the known MT-ND4* G11778A mutation is the most significant cause of LHON. The C3497T and C3571T mutations in Pedigree 1 were also both at hot-spots of MT-ND1; they may affect the respiratory chain in coordination with the primary mutation G11778A. In Pedigree 2, the two secondary mutations A10398G of MT-ND3 and T14502C of MT-ND6 may influence mitochondrial respiratory complex I, leading to the mitochondrial respiratory chain dysfunction which results in optic atrophy together with G11778A. Therefore, not only the common primary LHON mutation is responsible for the visual atrophy, but other secondary mtDNA mutations should also be considered when giving genetic counseling.