ND1 G3635A mutation in the mitochondrial DNA in three Chinese pedigrees of Leber's hereditary optic neuropathy
- Author:
- No author available
- Journal Title:
- Chinese Journal of Ocular Fundus Diseases
- Issue:
- 5
- DOI:
- 10.3760/cma.j.issn.1005-1015.2011.05.004
- Key Word:
- 视神经萎缩,遗传性,Leber/病因学;DNA,线粒体;突变;Optic atrophy,hereditary,Leber/etiology;DNA,nitochondrial;Mutation
Abstract： Objective To screen mitochondrial DNA mutations in 3 Chinese pedigrees with Leber's hereditary optic neuropathy (LHON) carrying the ND1 G3635A mutation. Methods88 members (53maternal relatives and 35 paternal relatives)in 3 pedigrees were enrolled. The ophthalmologic examinations were performed for all members, including visual acuity (standard logarithmic visual acuity charts), fundus photography (Canon fundus camera), visual field (Humphrey Visual Field Analyzer), color vision (Yu zhiping color vision plate), and visual evoked potentials (Roland Consult RETI port gamma, flash VEP).16 members had LHON, 72 members did not have LHON. 135 healthy people from Wenzhou were included as the control group. Genomic DNA was extracted from peripheral blood leukocytes of all subjects. G3635A mutation was screened by PCR-amplification of mitochondrial DNA for all subjects. Mitochondrial haplotypes and other mutations in the entire mitochondrial genome were also determined by PCR using 24pairs of primers for the probands. ResultsAnalysis of mitochondrial DNA (mtDNA) in 3 pedigrees revealed the presence of ND1 G3635A mutation in 3 probands and all maternal relatives, but not in paternal relatives and healthy controls. Proband's haplogroup belong to East Asia group N9a3, D4, and R11a. In addition to the G3635A mutation, probands also had other variants including 12 variants in D-loop region, 6variants in RNA gene, and 36 variants in protein-encoding gene. ConclusionsG3635A mutation was identified in probands and maternal relatives of 3 pedigrees of LHON. It showed that G3635A mutation was the pathogenic molecular basis for those patients.
- [1]刘燕,庄淑流,童绎,等.线粒体ND1基因T3866C突变可能是Leber's遗传性视神经病和四肢畸形跛行相关的突变[J].2010,(2).
- [2]赵福新,周翔天,瞿佳,等.中国Leber遗传性视神经病变G11696A突变两个家系分析[J].2007,(5).
- [3]D C, Wallace,G, Singh,M T, Lott,etc.Mitochondrial DNA mutation associated with Leber's hereditary optic neuropathy.[J].1988,242.
- [4]Zhao F,Guan M,Zhou X.Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation.[J].2009,389(3).
- [5]Y, Mashima,K, Yamada,M, Wakakura,etc.Spectrum of pathogenic mitochondrial DNA mutations and clinical features in Japanese families with Leber's hereditary optic neuropathy.[J].1998,17.
- [6]Zhu Y,Yang J,Tong Y.Confirmation of the mitochondrial ND1 gene mutation G3635A as a primary LHON mutation.[J].2009,386(1).
- [7]Michael D. Brown,Antonio Torroni,Calvin L. Reckord,etc.Phylogenetic analysis of Leber's hereditary optic neuropathy mitochondrial DNA's indicates multiple independent occurrences of the common mutations[J].1995,6(4).
- [8]D A, Mackey,R J, Oostra,T, Rosenberg,etc.Primary pathogenic mtDNA mutations in multigeneration pedigrees with Leber hereditary optic neuropathy.[J].1996,59.
- [9]Rieder MJ,Nickerson DA,Tobe VO,etc.Automating the identification of DNA variations using quality-based fluorescence re-sequencing: analysis of the human mitochondrial genome.[J].1998,26(4).
- [10]T, Hirokawa,S, Boon-Chieng,S, Mitaku.SOSUI: classification and secondary structure prediction system for membrane proteins.[J].1998,14.
- [11]Jia X,Li S,Wang P,etc.mtDNA m.3635G>A may be classified as a common primary mutation for Leber hereditary optic neuropathy in the Chinese population.[J].2010,403(2).
- [12]Sun C,Wu SF,Salas A,etc.Updating the East Asian mtDNA phylogeny: a prerequisite for the identification of pathogenic mutations.[J].2006,15(13).
- [13]Xiangtian Zhou,Juanjuan Zhang,Jia Qu.Extremely Low Penetrance of Leber's Hereditary Optic Neuropathy in 8 Han Chinese Families Carrying the ND4 G11778A Mutation[J].2009,116(3).
- [14]Kubacka I,Lightowlers RN,Turnbull DM,etc.Reanalysis and revision of the Cambridge reference sequence for human mitochondrial DNA (letter)[J].1999,23(2).
- [15]Qu J,Zhou X,Zhao.Low penetrance of Leber's hereditary optic neuropathy in ten Han Chinese families carrying the ND6 T11484C mutation.[J].2010,1800(3).
- [16]Zhang Q,Li S,Guo X,etc.Molecular epidemiology of mtDNA mutations in 903 Chinese families suspected with Leber hereditary optic neuropathy.[J].2006,51(10).